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Fast-track your biotech investments with VC Insights. Access expert guidance, vetted CROs, and data-driven strategies to invest smarter and move faster in GPCR drug discovery. Home About Services News Get in Touch Welcome VC Insights Fast Track Your Next Biotech Bet Get decision-grade data, vetted CROs, and expert guidance—so you move fast and invest smarter. I help you avoid costly delays, choose the right experiments, and unlock clear timelines that drive confident investment. Fast Track My Discovery The wrong CRO—or wrong experiments—can burn months and millions You're not here to fund academic detours. You're backing science that needs to move fast. But too often I hear: “We thought the experiments made sense—until the data didn’t help us decide.” “The CRO promised timelines they couldn’t hit.” “The team’s updates sound polished, but we can’t tell if they’re on track.” If you’ve said any of those, you’re not alone. That's where I come in : to pressure-test the science, align the strategy, and make sure every experiment earns its place. How I Drive Value Prioritize the Right Experiments Avoid noise. I help identify the experiments that truly matter—aligned to your milestones and inflection points. Translate project strategy into clear decision-driving assays Eliminate “nice to have” tests that stall timelines without payoff Match experiments to the specific phase and risk tolerance of the asset De-risk Your CRO Strategy I evaluate, select, and manage CROs that are fit-for-purpose—saving you time, cost, and rework. Audit and compare CRO options based on speed, quality, and fit Clarify deliverables and oversight to prevent rework and misfires Serve as a scientific bridge between VC, team, and CRO Move With Clarity and Speed Every week counts. I bring structure, decision frameworks, and momentum so your team stays on track. Build plans aligned to go/no-go moments, not busywork Drive regular check-ins that produce clear, actionable updates Anticipate delays and adapt quickly with contingency-ready paths " Yamina brings scientific clarity, leadership, and precision execution to complex pharmacological programs. I’ve worked with her on several discovery programs; in fragmented programs, she brought clarity and decision points that produced much better candidate progression. I am always delighted to work with Yamina as it always leads to an overall better and harmonious discovery program." - Terry Kenakin, PhD - UNC Chappel Hill Frequently Asked Questions 01 How quickly can you get started? I begin with a 30-minute call to understand your goals. From there, I deliver a roadmap or assessment within 1–2 weeks. 02 Do you only work post-investment? No—many VCs engage me before investing to assess targets, pressure-test science, or evaluate CRO readiness. 03 What if we already have a team? Perfect. I plug in as a strategic partner—complementing internal talent to bring execution clarity and scientific rigor. Let's turn complexity into confidence—with the data you need to move forward. Chat about My Discovery Send me a message First name* Last name Company name* Email* How Can I Help?* Send Message or Book My Call Menu Home Services About Ready to collaborate? Let’s talk about how I support GPCR discovery, pharmacology strategy, and cross-functional execution across biotech, VC, and CRO teams. Get in touch Connect LinkedIn Podcast Dr. GPCR Calendly ©2023-2025 All rights reserved by FindYooour, LLC & Dr. GPCR Corp Proudly created with Wix.com

Discover the mission, vision, and people behind the Dr. GPCR Ecosystem: uniting scientists, biotech, and innovators to advance GPCR research worldwide. Who We Are We are a global network of scientists, biotech innovators, pharma professionals, CRO leaders, and vendors—united by one mission: to make working on GPCRs easier, faster, and more collaborative. Dr. GPCR is both expert-led and community-first. We’re building together, with input from across the field. About Dr. GPCR Ecosystem We unite the GPCR Community to advance drug discovery Where GPCR Experts Move Science Forward Join the global community accelerating GPCR drug discovery through trusted insights, expert tools, and powerful connections. Join Free & Get Our Weekly News See Why it Matters 6,600+ followers 200+ Research Labs 1,500+ Scientists 50+ Biotech Companies Built by Scientists. Driven by Impact. Dr. GPCR began as a podcast. Now, it's a global ecosystem of scientists, biotech teams, CRO leaders, and trainees working to move GPCR science forward—together. We created this space to make trusted knowledge and collaborations easier to access—without noise, fluff, or hype. What We Believe The Ecosystem was built with five key beliefs: Scientific rigor first This is a space for data-driven work, not hype. Usefulness over flash Every piece of content and feature must be practical. Transparency builds trust We're open about who we are and what we do. Collaboration is key Progress in GPCR science requires a collective effort. Inclusion matters We welcome diverse voices, experiences, and expertise. We designed the Ecosystem to support your work —no matter where you are in your GPCR journey. Our Journey (So Far) From the first podcast episode to a global platform, it's all built by and for the GPCR community. 2020 First Podcast Episode Launched our podcast to share expert insights with the scientific community. 2021 2nd Annual Summit Increased our reach and impact with the GPCR Community 2022 Community Platform Expanded beyond content to create a dedicated space for GPCR scientists to connect. 2023 First Symposium Inaugural Dr. GPCR Symposium with over 100 attendees 2024 GPCR University Launched comprehensive courses and expert talks to deepen scientific understanding. 2025 Terry's Corner & Consulting Launched our exclusive program with Dr. Kenakin and offered to CROs consulting services See Full Timeline The Field Is Growing—but Fragmented As GPCR scientists, we know the problem: too much noise, too little time, and nowhere to connect that's built for us. We built Dr. GPCR to: Curate relevant data—not overwhelm you with it Connect researchers with CROs, peers, and biotech leaders Provide high-quality tools and expert insights on demand Whether you're in a lab, launching a startup, or prepping for due diligence, we built this for you. The GPCR Challenge Scientists waste an average of 12 hours per week searching for relevant GPCR research and connections. Our ecosystem cuts that time by 80%. You'll Be in Good Company From PhDs to CRO execs to rising biotech founders—this is a vetted, mission-aligned community built to help you move faster. Premium Members Include: ✔ Drug hunters at early-stage biotechs ✔ CRO leaders building assays and tools ✔ Academic researchers moving into translational work ✔ Teams preparing for fundraising or due diligence Expert Contributors Include: ✔ Terry Kenakin, with his exclusive series on GPCR pharmacology ✔ Sam Hoare, simplifying GPCR data analysis ✔ Global CROs and biotech leaders, contributing behind-the-scenes tools and insight What Makes the Ecosystem Different Built for Drug Discovery Designed by scientists in the GPCR space to accelerate your research goals Collaborative by Design Connects researchers, CROs, and biotech teams—not just profiles, real relationships. Results-Driven Every tool and content block is built to help you make a decision or move forward. ✔ GPCR-specific content ✔ Expert curation ✔ Vetted community What Joining the Ecosystem Looks Like 1 Join Free Sign up in seconds. You'll instantly receive the GPCR Weekly News (free version). 2 Get Verified We manually review each profile to ensure trust and scientific relevance. 3 Start Exploring Browse free content, community updates, and learn what's available. 4 Upgrade Anytime Premium unlocks exclusive courses, community features, and deeper insights. Start Your Journey Today Meet the Leadership Founder & Director Yamina Berchiche Get in Touch Board Member Anne M. Quinn Get in Touch Board Member Maria Waldhoer Get in Touch Co-Founder Attila Foris Get in Touch Board Member JoAnn Trejo Get in Touch Chief Matchmaker Mark Schmeizl Get in Touch Why Upgrade to Premium Everyone who joins receives the free Weekly News. Premium gives you everything else—the full toolbox for moving science forward. Free Membership Includes: ✔ Free version of GPCR Weekly News - straight to your inbox! ✔ Select news and content ✔ Ecosystem and podcast updates Premium Members Unlock: ✔ Full Weekly News access – All GPCR papers, events, jobs + expert commentary ✔ Dr. GPCR University – 5 on-demand GPCR courses, 1 project management course, 200+ expert talks ✔ Community tools – Member directories, messaging, and forums Partners Who Drive our Mission Partner Benefits Visibility to GPCR experts Direct connections Industry insights Explore Partnership Opportunities Ready to Join the Movement? Start free. Upgrade when you're ready. Dr. GPCR helps you stay ahead of the curve in science and strategy. Unlock Premium Access Join Free Now

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Monitor GPCR internalization in real time with pHSense™ – no-wash, TR-FRET reagents from Revvity. Fast, clear, live-cell receptor trafficking detection. Unlock microscopy-free real-time GPCR internalization with pHSense pHSense™ probes are optimized reagents for plate readers, specifically designed to study internalization using time-resolved fluorescence (TRF) detection. They offer high-sensitivity, no-wash detection of internalization events in a scalable, plate-based format. This technology supports robust analysis even at low endogenous receptor expression levels. Suitable for basal/constitutive and agonist-induced GPCR internalization Compatible with TRF plate readers No-wash protocol simplifies workflow Formats available for modified GPCR cell lines or unmodified primary cells Explore pHSense Products Powered by Revvity’s legacy of innovation in translational science. Dr. GPCR Ecosystem Partner Visit Website Precision Tools for Translational Science Revvity is a global leader in life science innovation, delivering tools and technologies that bridge the gap between discovery and real-world impact. With decades of expertise and an unwavering focus on precision, Revvity empowers scientists to simplify complex workflows, accelerate discovery, and drive breakthroughs in drug development, diagnostics, and disease biology. Whether you’re decoding signaling pathways or designing the next generation of therapeutics, Revvity isn’t just a provider—they’re your partner in discovery. Discover pHSense™ portfolio From binding to signaling to internalization: Cell-based fluorescence assays for complete GPCR characterization The principle of pHSense™ relies on the pH-dependent fluorescence activation of a europium-labeled antibody to monitor receptor internalization in live cells. Neutral pH = low signal: The probe is minimally fluorescent at extracellular neutral pH (≥7), which means it doesn't emit a strong signal when bound to the surface. Internalization into acidic compartments = signal activation: Upon receptor-mediated endocytosis, the probe is internalized into acidic intracellular compartments (like early/late endosomes and lysosomes). The europium complex becomes increasingly fluorescent as the pH drops, enabling dynamic tracking of internalization. Time-Resolved Fluorescence (TRF) = High Signal-to-Background: Europium’s long-lived fluorescence allows TRF detection, which effectively filters out short-lived background signals. This results in high sensitivity and specificity in no-wash, plate-based live-cell assays. pHSense™ Eu Anti-FLAG Designed for the detection of FLAG-tagged receptor and membrane protein internalization. View Product pHSense Eu SNAP Labeling Reagent Can be used to label receptors and membrane proteins carrying an extracellular SNAP sequence with a pHSense probe to monitor their internalization View Product pHSense Fab Anti-Human or Anti-Mouse IgG Fab fragments for monitoring GPCR and antibody internalization in unmodified cells The Fab Anti-Human IgG Eu-conjugate can be used in combination with a neutral anti-GPCR to address unmodified receptors in primary cells View Product The Fab Anti-Mouse IgG2 Eu-conjugate is suited to study mouse biologics targeting GPCR and confirm their internalization effects on receptors. View Product The pHSense™ Advantage Clarity. Consistency. Compatibility. Purpose-Built for Live-Cell Internalization Assays The pHSense™ family of europium-labeled, pH-sensitive reagents is designed to simplify and accelerate the study of GPCR and membrane protein internalization in live cells. These reagents are fully compatible with plate-based, no-wash workflows and use time-resolved fluorescence (TRF) to eliminate background noise—delivering clear, quantifiable signals as targets move into acidic intracellular compartments. What Sets pHSense™ Apart ✅ Time-resolved detection minimizes background noise, which enhances detection sensitivity. ✅ No-wash protocol preserves cell integrity and kinetic detection. ✅ High-throughput ready: faster time-to-results and streamlined data acquisition. ✅ Comprehensive validation: validated for GPCRs, but also antibodies and ADCs. ✅ Versatility across suspension and adherent cells The Full GPCR Toolkit by Revvity Every step of the signaling cascade. One trusted source. GPCRs are among the most powerful and complex targets in biomedical research. Revvity offers a comprehensive reagent portfolio to match that complexity—supporting every stage of the signaling pathway, from ligand binding and G-protein activation to intracellular signaling readouts. With formats including TR-FRET, radioligand binding, cAMP, IP-One, and phospho-protein assays (ERK, AKT, CREB, MEK), this toolkit is built for speed, reproducibility, and translational insight. Proprietary no-wash technologies help reduce hands-on time while maintaining exceptional data quality—so you can move fast without compromise. View Reagents Explore Revvity’s GPCR Assay Technologies Tools designed to illuminate every step of GPCR signaling—from binding to downstream response. Ligand binding Measure receptor engagement with high sensitivity using TR-FRET, radioligand, and Fluorescent Tag-lite® formats. G-Protein Activation Quantify Gs, Gi, and Gq activation in real time with cAMP, GTP, and IP-One assays. Arrestin Recruitment Detect β-arrestin recruitment with TR-FRET and luminescence assays tailored for biased signaling studies. Intracellular Signaling Track key downstream events like ERK, AKT, and CREB phosphorylation with high-throughput precision. Build Your GPCR Assay Workflow Meet the Team behind pHSense™ Eric TRINQUET Sr Director Life Sciences Reagents, Revvity Eric Trinquet is a recognized expert in the field of immunoassays and fluorescence technologies. He currently leads Revvity's Research and Development activities, focusing on biochemical and cellular assay platforms related to Life Sciences Reagents. Before joining Revvity, Eric worked for Cisbio Bioassays first as Director of Technological Development and then as R&D Director. His career is marked by significant contributions, from introducing HTRF technology in the field of high-throughput screening to developing innovative solutions such as the IP-One kit for studying G Protein-Coupled Receptors (GPCRs) and the Tag-lite platform. Elodie DUPUIS R&D Senior project manager, team leader. Elodie Dupuis earned her Master’s degree in biology and biotechnology engineering from the University of Sciences of Nîmes and the Ecole des Mines engineering school (France) in 2009. She then joined Cisbio Bioassays, and later Revvity, as project leader and team manager in the Research & Development department, leading her team on the development of innovative HTRF™ and AlphaLISA™ kits for pharma, biotech, and academic partners. Through her research contributions, she has co-authored numerous scientific publications and holds several patents as an inventor. She has been leading collaborative projects with public research institutes and pharmaceutical companies, most notably the joint Revvity/Institute of Functional Genomics team, EIDOS. In 2020, together with her team, she initiated a long-term research effort that enabled the creation of a new and innovative portfolio for GPCRs, antibody drug conjugates, and several other applications: pHSense™. 2025 marked the commercial launch of the first pHSense products by Revvity. Mathis LAFFENETRE Product Manager, Immunoassay Reagents. Mathis holds a biotechnology engineering degree from the National School of Biomolecule Technology of Bordeaux and an MS in biomedical business management from the Grenoble School of Management. He joined Revvity (then Cisbio) in 2016 as part of the scientific marketing effort to build brand recognition for the HTRF technology and accelerate the company’s reagents use in academic labs, biotech companies, and pharma. In the following years, he held several marketing and strategic positions in France and the US, primarily related to the Immunoassay portfolio. As of 2025, he is part of the Immunoassay & Imaging Reagents Portfolio group as a product manager for the GPCRs, and is responsible for supporting the adoption and expansion of the reagent portfolio into the hands of scientists and researchers. Inside the Science: A Conversation with Revvity's Dr. Eric Trinquet From Rare Earth Probes to Internalization Assays: The pH Sense Story If you’ve ever used HTRF or wondered what goes into making a product worthy of your next experiment, this is your backstage pass. More about this conversation Our Partnership Dr. GPCR Spotlights Revvity’s pHSense™ Reagents for Real-Time GPCR Internalization A new reagent family designed to unlock high-throughput internalization workflows—now featured across the Dr. GPCR Ecosystem Boston, MA – September 2025 — Dr. GPCR, the global nonprofit platform dedicated to advancing GPCR research and drug discovery, is proud to spotlight the launch of pHSense™, a new reagent family from Revvity designed to bring unprecedented clarity, speed, and scalability to the study of receptor internalization. Internalization is a core—but often overlooked—dimension of GPCR biology. Traditionally, studying it has meant long workflows, low throughput, or expensive imaging platforms. pHSense™ changes that by combining europium-based, pH-sensitive probes with no-wash, live-cell protocols and TRF-based detection—making it possible to monitor internalization in real time, in standard plate-based assays. “When we saw dose-dependent internalization in endogenous GLP1R cells—without microscopy—that was the turning point,” said Dr. Eric Trinquet, Director of Research and Development at Revvity. “We knew pHSense could offer something truly new to the GPCR field.” A Tool Designed for Real Research Needs Built on more than two decades of GPCR assay innovation, pHSense™ was developed to overcome three persistent barriers in internalization studies: Complexity of imaging-based workflows Lack of scalability for high-throughput screening Difficulty detecting endogenous receptor activity With pHSense™, scientists can finally move beyond proxy readouts and track GPCR internalization as it happens—even at physiological expression levels. All four formats are validated in well-established models like GLP1R and Mu opioid receptor (MOR), and are compatible with HTRF plate readers already used in most labs. Related Articles How Breakthroughs Happen: Eric Trinquet on Innovation, Serendipity & GPCRs Discover how Dr. Eric Trinquet, creator of HTRF and IP-One assays, turned failure into breakthrough tools for GPCR science. Learn why play, serendipity, and partnerships fuel innovation—and how this mindset can transform your research and biotech career. Dr. GPCR Podcast Oct 16, 2025 4 min read The Truth About GPCR Product Launches: Years in the Making What it really takes to launch a GPCR product—years of failure, science, and strategy. Go behind the scenes of pH-Sense with Revity’s Dr. Eric Trinquet. Dr. GPCR Podcast Oct 8, 2025 4 min read Innovative Data-Driven Solutions: The pHSense Revolution A powerful new tool tracks GPCR internalization in native cells—no imaging, no overexpression. Learn how pH Sense changes the game for drug discovery. Dr. GPCR Podcast Sep 26, 2025 3 min read Dr. GPCR Ecosystem Partner Contact Revvity

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Live webinar with Dr. Terry Kenakin on detecting, quantifying, and applying receptor signaling bias in GPCR drug discovery. May 28, 2026. Free. < Back to Webinars 📅 Thursday, May 28, 2026 at 3:00:00 PM UTC 🤝 Webinar in collaboration with: Eurofins DiscoverX Receptor Signaling Bias: A Valuable and Accessible Property of New Drug Candidates Turning functional selectivity into a practical decision-making tool in GPCR drug discovery Beyond Potency: What Ligand-Dependent Signaling Reveals About Drug Candidates G protein-coupled receptors can signal through multiple intracellular pathways, and ligands do not necessarily engage those pathways to the same extent. This phenomenon, receptor signaling bias or functional selectivity, is now recognized as a meaningful property of many drug candidates and a potential route to improved efficacy, better tolerability, and new opportunities in challenging targets. Bias is not an anomaly. It is a consequence of ligand-dependent receptor conformations and allosteric probe dependence, and it can be revealed with the right combination of functional assays. This webinar explains the biological basis of signaling bias, shows how to detect and quantify it using reliable functional assays, and discusses how these data can guide lead selection and optimization. Practical assay strategies, interpretation pitfalls, and the value of comparing pathway outputs quantitatively, rather than relying on potency alone, sit at the center of the session. The Biology Behind Bias Ligands produce differential pathway engagement at a single receptor because they stabilize distinct receptor conformations. These conformations determine which downstream pathways are favored and which are muted. Due to this potential inherent bias, it is best practice to evaluate multiple pathways using different GPCR assays to obtain a better understanding of the ligand effects on the GPCR system. Speaker Dr. Terry Kenakin Professor of Pharmacology & Pharmacology Course Coordinator Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill. Dr. Kenakin trained in chemistry and pharmacology at the University of Alberta and completed postdoctoral work at University College London in the laboratory of Sir James Black. He spent 25 years in drug discovery at Glaxo (now GlaxoSmithKline) before joining UNC Chapel Hill, where he teaches and leads research in receptor pharmacology. His work is central to the quantitative framework used today to describe receptor signaling bias, allosteric function, and agonism. He proposed one of the first mechanistic explanations of biased signaling and co-authored the widely-applied simple method for quantifying functional selectivity. He is the author of A Pharmacology Primer, Editor-in-Chief of the Journal of Receptors and Signal Transduction, and a Fellow of the British Pharmacological Society, recognized with the Goodman and Gilman Award from ASPET and the Gaddum Memorial Award. Within the Dr. GPCR ecosystem, Terry hosts Terry's Corner, a live room where GPCR scientists get direct access to him. It's where the mechanistic questions that usually sit beneath the data get asked out loud, and where receptor theory, biased signaling, and the pharmacology of real drug discovery decisions are worked through together. Organizers Eurofins DiscoverX Eurofins DiscoverX is a one-stop-shop for GPCR drug discovery and development, with 25+ years of expertise and validated cell-based assays spanning basic research through therapeutic discovery, optimization, and regulatory submission. Their assays are industry-standard, accepted for regulatory potency testing, and backed by thousands of peer-reviewed publications and partnerships with leading pharma and biotech companies. 1,500 human GPCR products covering ~90% of the GPCR-ome, including orphan receptors and ortholog variants Multiple mechanisms of action: cAMP accumulation, β-arrestin recruitment, receptor internalization, ligand binding, calcium flux, and pharmaco-chaperone discovery Flexible formats: cell line assay kits, ready-to-use eXpress kits, qualified bioassays, membrane preps, detection kits, and custom products Applications across target identification, HTS, lead optimization, ligand bias and allostery evaluation, safety assessment, and regulatory potency testing Dedicated portfolio for obesity and diabetes GPCR targets (GLP-1R, GIPR, GCGR, MC4R, AMY receptors, and more) Dr. GPCR Dr. GPCR is a membership-based nonprofit ecosystem dedicated to advancing GPCR-targeted drug discovery. It provides curated industry intelligence, expert-led masterclasses, and structured engagement opportunities for scientists and biotech leaders working across pharmacology, translational research, and therapeutic development. Curated intelligence on GPCR drug discovery trends and developments Expert-led webinars and masterclasses with leading researchers Structured networking for scientists and biotech professionals Nonprofit model, community-first, member-driven Free membership tier available Previous Webinar Next Webinar Don’t Miss the Next Live Session Dr. GPCR membership gives you access to all upcoming live, interactive webinars. Free. Takes less than a minute to join. Cancel anytime. Sign Up for Free

Turn GPCR discovery chaos into clarity—Yamina’s Corner offers expert GPCR strategy, CRO guidance, and tailored scientific support to accelerate your pipeline. Home About News Get in Touch Welcome Turn GPCR Chaos Into Insights Expert strategic and scientific consultancy to accelerate your pipeline Book My Consultation Critical Bottlenecks in Your GPCR Pipeline ❌ Overwhelming pharmacology Data ❌ Suboptimal CRO Partnerships ❌ Stalled Pipeline Progression ❌ Uncertainty in GPCR Investments Advisory Focus Areas Expert support for Biotech innovators, VC investors and CRO partners Biotech Pipeline Acceleration For Biotech Leaders & Scientists Actionable Data Insights: Translate complex GPCR pharmacology into clear decisions for lead optimization and candidate selection. Accelerated Program Progression: Design robust assay cascades and establish key go/no-go points to speed up your pipeline. Optimized CRO Collaboration: Streamline internal R&D and external CRO workflows to prevent delays and ensure preclinical success. Fuel Discovery VC Due Diligence & De-risking For Venture Capital Firms De-risk GPCR Investments: Identify critical scientific red flags and technical gaps in GPCR assets before committing capital. Actionable Scientific Validation: Ensure target companies execute the right GPCR pharmacology experiments to generate robust, decision-making data. Clear Platform Assessment: Gain rapid, independent insight into GPCR platform risks and true therapeutic potential to inform investment strategy. Fast-Track Discovery CRO Partnership & Optimization For Contract Research Organizations Elevate Scientific Offerings: Refine and optimize your GPCR assay platforms and in vitro models to deliver superior data quality and results. Enhance Client Project Delivery: Streamline workflows and improve scientific execution to increase client satisfaction and secure repeat business. Differentiate Your Market Position: Showcase your specialized GPCR expertise to stand out from competitors and attract high-value biotech and pharma partners. Power Discovery How We Work: Your Path to GPCR Success 1 Initial Strategic Alignment We begin with a focused discussion of your current GPCR program and critical challenges, identifying precise areas for collaboration. 2 Define Actionable Objectives Together, we clarify specific, measurable goals, from target validation and assay development to CRO selection or portfolio strategy, ensuring a tailored approach. 3 Collaborative Execution & Impact I integrate directly into your discovery process to remove roadblocks, enhance execution, and generate actionable scientific data, driving confident decisions and sustained preclinical progress. Advance My Discovery My Approach: Precision Guidance for GPCR Programs I provide the focused, scientific expertise that accelerates complex GPCR discovery programs, ensuring clarity and de-risking your path from target to candidate. I integrate seamlessly with biotech, VC, and CRO teams as a trusted, objective partner. Integrated Strategic Partnership We collaborate directly with your scientific and leadership teams. This partnership prevents bottlenecks and optimizes resource allocation, ensuring every strategic decision efficiently propels your program forward and aligns with critical business objectives. Biology-First, Data-Driven Solutions Every recommendation is rooted in GPCR biology, pharmacology experience. This provides evidence-based strategies leveraging deep GPCR expertise to overcome specific scientific challenges and maximize your program's potential. Accelerated Preclinical Progression I streamline critical operational processes, from advanced assay design and CRO management to rapid go/no-go decision-making. This focused execution accelerates preclinical milestones and maximizes the efficiency and return on your R&D investment. Core Values: The Foundation of Every Successful Partnership My advisory is built on principles that ensure clarity, minimize risk, and drive enduring results in GPCR drug discovery. Scientific Integrity Every recommendation is rigorously evidence-based, not reliant on assumptions. This ensures robust, defensible decisions that de-risk your program from early discovery to regulatory milestones. Operational Discipline I instill structure and consistency across every phase of your discovery process. This approach eliminates inefficiencies and standardizes workflows, accelerating your path to a preclinical candidate. Collaborative Partnership I operate as an embedded, invested partner with your team. Your program's success is my priority, fostering a transparent, results-driven environment that maximizes collective expertise and accelerates progress. About Yamina A. Berchiche I'm Yamina A. Berchiche, and I understand the intricate challenges of GPCR drug discovery. Small missteps can derail entire programs: underperforming assays, off-track CROs, and data that fails to drive decisions. That's precisely where my expertise becomes your strategic advantage. With over two decades dedicated to GPCR pharmacology across biotech, academia, and the non-profit sector, I bring unparalleled scientific depth and operational precision to every project. My work focuses on integrating directly with your team as a strategic partner. Whether it's optimizing CRO selection, building robust internal capabilities, or translating complex data into decisive program advancements, I help you eliminate friction, align efforts, and accelerate your path to success. As the founder of Dr. GPCR, I also offer a unique, broad perspective and trusted relationships within the field. This allows me to connect you with critical insights and key collaborators, further accelerating your progress in GPCR drug discovery. Let's Talk Discovery What Partners Say Here’s what it’s like to work together — from people I’ve supported on both sides of the bench. Anne Marie Quinn, CEO Montana Molecular As a CRO, we were delivering high-quality data across complex biotech programs, but translating that data into aligned, timely decisions across stakeholders wasn’t always straightforward. After partnering with her, communication became clearer, deliverables were better defined, and collaboration across teams ran more smoothly. She helped streamline complex projects and made the CRO–client relationship more effective and productive. Terry Kenakin, PhD UNC Chappel Hill In complex pharmacological discovery programs, scientific ambiguity and fragmented execution can quietly erode progress. Yamina brings the clarity, rigor, and structured decision-making that keeps programs on track. Across multiple discovery efforts, she established clear decision gates and alignment across teams, materially strengthening candidate progression and prioritization. Her involvement consistently elevates both the scientific discipline and the quality of portfolio-level decisions. Murat Tunaboylu, CEO Antiverse Before engaging Yamina, our team faced hurdles navigating complex early discovery decisions. We had critical program choices ahead and needed clearer direction. Bringing her in marked a meaningful shift. We made confident progress on a pivotal program and gained clarity on our next strategic focus. Yamina was instrumental in unifying our scientific and operational teams, strengthening alignment and driving momentum across execution. Abishek Iyer, CEO Ashta Therapeutics Before working with Yamina, we had solid internal momentum but needed to better align our biology, assay priorities, and compound strategy into a cohesive, decision-driven plan. Her input helped us structure the screening funnel, define clear go/no-go criteria, and integrate ADME and mechanistic assays in a way that reflected both biological rationale and operational realities. She has been a true thought partner — not only on tactical execution, but on pressure-testing hypotheses, challenging assumptions, and maintaining disciplined forward progress. Book Book My 30 Minutes Strategy Call Menu Home Services About News Ready to collaborate? Let’s talk about how I support GPCR discovery, pharmacology strategy, and cross-functional execution across biotech, VC, and CRO teams. 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<< Back to podcast list Strategic Partner(s) Re-cap of Endocrine Metabolic GPCR 2024 with the Organizers About Dr. Aylin Hanyaloglu Dr. Aylin Hanyaloglu has been a Principal Investigator at Imperial College London since 2007. She received her BSc in Human Biology from King’s College London in 1997, and while her Ph.D. commenced at the MRC Human Reproductive Sciences Centre, Edinburgh, a move to Perth, Australia resulted in her Ph.D. in Molecular Endocrinology being awarded in 2002 with Distinction from the University of Western Australia. Dr. Hanyaloglu undertook her postdoctoral training at the University of California, San Francisco with Professor Mark von Zastrow where she identified novel core cellular machinery critical for G protein-coupled receptor trafficking and signaling. Her research focuses on understanding the fundamental cell biological mechanisms regulating GPCR activity, including spatial control of GPCR signaling and receptor crosstalk, and applying these mechanisms for distinct GPCRs in diverse physiological and pathophysiological systems, with particular focus on women's health, pregnancy, and nutrient sensing in the gut. Her work is currently funded by Biotechnology and Biological Sciences Research Council (BBSRC), Diabetes UK, Wellcome Trust, and the Medical Research Council. Dr. Aylin Hanyaloglu on the web LinkedIn Endocrine Metabolic GPCRs Researchgate Twitter Imperial College London Elsevier Loop Dr. GPCR About Dr. Caroline Gorvin "Dr. Caroline Gorvin is a Wellcome Trust & Royal Society Sir Henry Dale Fellow at the Institute of Metabolism and Systems Research, University of Birmingham. She obtained her PhD in 2012 from the University of Oxford, where her research focused on the cellular mechanisms by which mutations in a chloride-proton antiporter cause the renal disorder Dent’s disease. Caroline continued to undertake postdoctoral research in Oxford, investigating the signalling and trafficking of the G protein-coupled receptor (GPCR), calcium-sensing receptor, and its role in calcium homeostasis. Caroline moved to the University of Birmingham in 2018 to establish her research group investigating metabolic GPCRs. Her current research focuses on how metabolic GPCRs cross-talk and interact to regulate appetite and bone metabolism." Dr. Caroline Gorvin on the web University of Birmingham Endocrine Metabolic GPCRs Society of Endocrinology Google Scholar ResearchGate Loop Twitter Dr. GPCR About Dr. Alejandra Tomas "Dr. Alejandra Tomas is a molecular cell biologist and Senior Lecturer at the Department of Metabolism, Digestion and Reproduction, Imperial College London. She obtained a PhD in Biochemistry from University College London and spent several years in Switzerland working on the study of membrane trafficking processes in pancreatic beta cells before returning to the UK, first to her Department at UCL and then to lead a laboratory at Imperial following the receipt of an MRC New Investigator Award in 2015." Dr. Alejandra Tomas on the web Imperial College London Endocrine Metabolic GPCRs ResearchGate Google Scholar LinkedIn Twitter Dr. GPCR Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Alix A. J. Rouault About Dr. Alix A. J. Rouault "My contribution to science began during the equivalent of U.S. masters training at the Université de Bretagne Occidentale (UBO; France). Under the leadership of Dr. Karine Pichavant , I contributed to the development of a drug to treat hypovolemic shock after severe hemorrhage. During this time, Dr. Olivier Mignen , the director of another research unit at the UBO recommended me to Dr. Julien Sebag , a researcher at the University of Iowa. I spent two years working with Dr. Sebag as an exchanged scholar while my student visa was in the work, during which time I thoroughly reviewed the literature on the melanocortin receptor accessory protein 2 (MRAP2), resulting in my first peer-reviewed publication in Biochimica et Biophysica Acta (BBA). I then undertook my first project where I demonstrated that MRAP2 regulates the signaling of multiple G protein-coupled receptors (GPCRs) through different structural regions. This project yielded my first, first author publication in BBA – Molecular Cell Research, and a book chapter for Neuromethods on a technique I adapted to measure the mitochondrial pyruvate oxidation in primary neurons. In 2017 I officially joined the PhD program in the Department of Molecular Physiology and Biophysics at the University of Iowa Carver College of Medicine, under the mentorship of Dr. Sebag. During my PhD, I continued my studies on MRAP2. I contributed to an In-vivo project that showed that MRAP2 regulates the growth hormone secretagogue receptor-1a (GHSR1a), the results of which are published in Nature Communications. Concurrently, I described the mechanisms by which MRAP2 regulates GHSR1a signaling; this project brought forth our NanoBiT-based arrestin recruitment assay. At the time, NanoBiT was a prototype technology we gained access to by collaborating with Promega. This powerful tool allowed us to create an assay that kinetically measured the arrestin recruitment to an activated GPCR for the first time. Using this novel technique, I showed that MRAP2 biased GHSR1a signaling and shut down its constitutive activity; this work resulted in a first author publication in Science Signaling. While writing my thesis, I published another paper in the Journal of Biological Chemistry which described the molecular mechanisms of MRAP2 regulation of the GHSR1a, and where I notably developed the C-terminal gate theory. This theory states that the post-translational modification of GHSR1a’ C-terminal tail is not a docking space for the arrestins, but rather a necessary modification leading to a structural change granting the arrestins access to the core of the receptor. Some of my data were also used in an In-vivo study published in iScience, showing the relevance of the MRAP2 regulatory effect on GHSR1a in pancreatic islets. Dr. Cone’s lab was a clear choice for a postdoc. Dr. Cone was the first to clone the melanocortin receptors (the GPCRs that led to the discovery of MRAP2), and his lab works is highly In-vivo oriented. Since I joined the lab, I became proficient in many In-vivo techniques, I adapted my arrestin recruitment assay to a high throughput screening format for drug discovery, I have started molecular work on the melanocortin receptors. I also invested a tremendous amount of time in developing my leadership skills. I spent time running for the chair of International Affairs for the U-M Postdoctoral Association (UMPDA). Further, I applied to create a scientific session at the American Physiology Summit (APS) 2024 dedicated to GPCR biased signaling. Dr. Lauren Slosky and Dr. Joshua Gross were enthusiastic about the idea and jumped on board. Our session was picked up by the APS. We were pleasantly surprised by the interest generated by our scientific session, Dr. Michel Bouvier accepted to open our session and will be followed by Dr. John McCorvy , Dr. Dylan Eiger , and Joshua Gross. We are very excited about this event. At this point in my career, I am creating connections with biomedical industry, assessing professional opportunities, and seriously weighing strengths of career options across sectors; however, academia does not make information about industry widely accessible to trainees. This is, in part, why I ran for, and was elected Chair of International Affairs of the University of Michigan Postdoc Association. I want to connect more trainees with diverse career resources to support professional decision-making. I am hopeful that my efforts to support the professional opportunities of my peers, in combination with my own scientific endeavors, will inform my future career decisions." Dr. Alix A. J. Rouault on the web University of Michigan Carver College of Medicine ResearchGate Google Scholar Dr. GPCR Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Cheloha builds nanobody-GPCR ligand conjugates that rescue weak peptides, engineer receptor selectivity, and probe endosomal signaling at NIH. << Back to podcast list Strategic Partner(s) Ross Cheloha: Nanobody-GPCR Conjugates and the Engineering of Receptor Selectivity The parathyroid hormone receptor sits at the intersection of calcium homeostasis, bone metabolism, and a set of pharmacological questions that have resisted clean resolution for decades. How does receptor conformation shape the duration of downstream signaling? Why do some ligands continue activating from the endosome while others don't? And can selectivity for one receptor subtype be engineered without redesigning the ligand from scratch? Ross Cheloha approaches these questions from a chemical biology perspective - using synthetic peptide analogs, camelid single-domain antibodies (nanobodies), and bifunctional conjugates that split the binding event into two independently tunable pieces. In this conversation, he describes how attaching a moderately active peptide to a receptor-targeted nanobody can boost potency by up to 10,000-fold, and how the selectivity of the nanobody - not the ligand - is what engineers receptor subtype specificity. For Cheloha, the motivation traces back to a habit he carried from childhood: writing reports on exotic diseases and what scientists were doing to treat them. The experiment that mattered most was not a drug candidate or a clinical advance - it was a designed conjugate that worked when there was no clear reason it had to, every control behaving exactly as expected. About the Guest Ross Cheloha is a tenure-track investigator at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at the National Institutes of Health. His research combines peptide chemistry, chemical biology, and nanobody engineering to build mechanistic tools for studying GPCR signaling, with a particular focus on the parathyroid hormone receptor and its downstream consequences for calcium homeostasis and bone biology. Trained in the Gelman lab at the University of Wisconsin-Madison and later in the Ploegh lab at Harvard Medical School and Boston Children's Hospital, he developed methods for covalently functionalizing camelid single-domain antibodies with synthetic ligands to probe receptor conformation, endosomal activity, and the duration of signaling responses. His work has demonstrated that nanobody-ligand conjugates can rescue pharmacologically weak peptides, engineer receptor subtype selectivity, and open mechanistic questions that conventional ligand design cannot easily address. Scientific Themes of the Conversation Peptide analog engineering and the stabilization of GPCR ligands using non-natural amino acids Receptor conformation selectivity: G-protein coupled versus uncoupled states and their downstream consequences Camelid single-domain antibodies (nanobodies) as a platform for GPCR chemical biology Nanobody-ligand conjugates as bifunctional tools for potency rescue, selectivity engineering, and mechanistic dissection Duration of signaling and endosomal GPCR activity: what wash-and-measure paradigms have been missing Tissue-specific receptor targeting and the pharmacological logic of reducing GPCR side effect profiles Key Insights from the Conversation 1. Conformation selectivity changes the duration of the signal PTH receptor exists in G-protein coupled and uncoupled states, and peptide analogs incorporating non-natural amino acids show differential affinity for each conformation. The analogs that preferentially bind the uncoupled state produce markedly prolonged signaling responses - in cells and in animal experiments - compared to ligands that do not. The biology may have been using this distinction all along: two natural ligands for the same receptor already show subtly different conformation preferences and different physiological profiles in vivo. 2. One nanobody, four orders of magnitude Connecting a short, weakly active PTH fragment (11 amino acids, approximately 100 nanomolar potency) to a receptor-targeted nanobody produced sub-nanomolar potency in cell-based assays - an improvement of up to 10,000-fold from a single engineering step. The working model is that the nanobody anchors the conjugate at the receptor surface, positioning the ligand for activation that would otherwise be too transient to drive a strong response. The selectivity comes from the nanobody's binding specificity, not from chemical modification of the peptide itself. 3. Selectivity without redesigning the drug PTH 1-34 activates both PTHR1 and PTHR2 with high potency, and engineering subtype selectivity through chemical modification of the peptide is technically demanding. Attaching a short PTH fragment to a PTHR1-selective nanobody produces a ligand selective for that subtype; the same fragment attached to a PTHR2-selective nanobody redirects it entirely. The implication generalizes: wherever a selective nanobody exists for a GPCR target, it can be used to introduce specificity into an otherwise promiscuous ligand without restructuring the pharmacophore. 4. Endosomal signaling is being missed Conventional GPCR assay design - stimulate, wash, measure endpoint - systematically misses signaling that continues after receptor internalization into the endosome. Cheloha's position is that the standard assumption linking tighter binding to longer signaling is incomplete. Endosomal activity is a distinct mechanistic process, and the tools to dissect it - bifunctional conjugates with independently tunable affinity components - are not available with conventional single-piece ligands. This is the central mechanistic priority he is bringing to his NIH lab. 5. Tissue-specific targeting as a strategy for reframing side effects The primary dose-limiting side effect of PTH-based therapies is hypercalcemia, driven in part by receptor activity in kidney tissue rather than bone. Connecting a ligand to a tissue-targeted nanobody could restrict receptor activation to bone and reduce unwanted calcium release. The pharmacological logic is sound, and the engineering framework to test it exists. Whether it holds in vivo remains to be demonstrated - Cheloha is careful to say so - but it represents a genuinely new angle on a long-standing problem in PTH pharmacology. 6. The experiment that had no reason to work - and did Among three scientific aha moments Cheloha described, the one with the clearest forward momentum was the first successful nanobody-PTH conjugate - designed not because a clear rationale existed, but because he wondered whether it was possible. No hypothesis guaranteed the result. Every positive and negative control performed exactly as designed. The conjugate worked. That single experiment, Cheloha said, opened more mechanistic doors than anything he had produced before - and it came directly from experience-built intuition rather than hypothesis-first design. Episode Timeline Timestamps are AI-generated from the transcript and are approximate. Verify against the final edited video before publishing. 00:00 Introduction 01:58 From pharmacy school to chemical biology: how the research path took shape 08:12 Academia versus industry - why freedom to ask non-translatable questions matters 09:43 The academic job search: 65 applications, six interview trips, and landing NIH 14:20 How a peptide chemist found the PTH receptor - and a collaborator who changed everything 17:20 Non-natural amino acids, protease stability, and receptor conformation selectivity 21:40 PTH receptor pharmacology: calcium spikes, bone biology, and why long-acting isn't always better 23:22 A detour into immunology and the discovery of camelid nanobodies 25:45 The first nanobody-GPCR ligand conjugate and an unexpected 10,000-fold potency gain 30:32 Engineering receptor subtype selectivity without redesigning the pharmacophore 36:10 Mechanistic priorities at NIH: endosomal signaling and duration of signaling 40:25 Are GPCRs still a good drug target? Biased agonism, endosomal signaling, and what remains 47:13 Three aha moments: first data, an email from Gardella, and the conjugate that worked Selected Quotes "I just thought of something - hey, I wonder if this would work. There was not necessarily an underlying scientific rationale for trying this. I wasn't thinking this is going to be a new drug. I just thought of something and said, I wonder." "I was convinced that I designed something that worked where it was not at all obvious that it was going to work. And that just opened up so many doors." "I don't think tight binding equals longer signaling is necessarily the whole story. I think in large part it's been missed." "Anything you can contribute to that end is hopefully going to provide a step forward in understanding disease and treating disease. The freedom and creativity - that's what I was really attracted to." About this episode Dr. Ross Cheloha is an Investigator at the National Institutes of Health in the Laboratory of Bioorganic Chemistry in Bethesda, MD, where he started in October 2020. He completed his postdoctoral training at MIT and Harvard Med School in the lab of Hidde Ploegh , where he developed new applications of single-domain antibodies (nanobodies). He earned his Ph.D. in Chemistry at the University of Wisconsin-Madison in the lab of Sam Gellman on the study of analogs of the GPCR peptide ligand parathyroid hormone. Work in his independent laboratory is focused on developing new pharmacological tools via chemistry and protein engineering to interrogate GPCR signaling. Ross and I chatted about his work and transition to an independent investigator; join me to learn more about class B GPCRs and Dr. Cheloha’s work. Dr. Ross Cheloha on the web NIDDK Cheloha Lab Google Scholar LinkedIn Twitter ResearchGate Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Dr. Fiona Marshall on structure-based GPCR drug discovery, the GABA-B heterodimer, the acetate that rewrote a receptor family, and why the same names keep filling GPCR conference agendas. << Back to podcast list Strategic Partner(s) Fiona Marshall: Three Decades Inside GPCR Drug Discovery This conversation traces how structure-based GPCR drug discovery moved from a stubborn crystallography problem to a generative platform — through the career of a scientist who helped engineer that shift. Dr. Fiona Marshall walks through the decade when membrane proteins kept failing to crystallize in detergent, and how Chris Tate's thermostabilization strategy finally made GPCR structures routine, the insight that seeded Heptares Therapeutics. The conversation moves across discoveries that shaped a generation of GPCR pharmacology: the GABA-B heterodimer, the free fatty acid receptors, the unexpected allosteric pockets that emerged once structures became available. It also confronts where the field still struggles — translating biased agonism from cell line to clinic, drugging orphan receptors without obvious phenotypes, and expanding the voices that define the field's agenda. For Dr. Marshall, the throughline is personal: she remembers the exact lecture at Bath where she first heard about the β-adrenergic receptor, and has spent three decades inside the rooms where GPCR drug discovery actually changed. About the Guest Dr. Fiona Marshall is VP and Head of Neuroscience Discovery at MSD, leading teams in West Point, Boston, and London. She co-founded Heptares Therapeutics and served as Chief Scientific Officer for twelve years, through the company's acquisition by Sosei, helping establish structure-based drug design as a productive strategy across GPCR families. Earlier, at GSK, she contributed to the identification of RAMP proteins, the GABA-B heterodimer, and ligands for orphan receptors including what are now known as FFA2 and FFA3. Her work spans GPCR structural biology, membrane protein stabilization, allosteric modulation, and the pharmacology of receptor families implicated in neuroscience, immunology, and metabolism. Scientific Themes of the Conversation Structure-based GPCR drug design and the thermostabilization breakthrough GPCR heterodimerization and the logic of accessory proteins (RAMPs, GABA-B1/B2) Allosteric modulation and non-orthosteric binding sites on GPCRs Biased agonism, target validation, and animal-to-human translation failure Orphan GPCRs and the missing pharmacology of ~100 unassigned receptors GPCRs in oncology, immunology, and microbiome-host signaling Key Insights from the Conversation Why Membrane Proteins Wouldn't Crystallize The bottleneck wasn't expression level, as most groups had assumed — it was the instability of the receptor in detergent. Chris Tate's thermostabilization strategy, which introduced stabilizing mutations selected by thermal assay, reframed the problem and opened the door to routine GPCR crystallography. Dr. Marshall is clear that the conceptual reframing, not a brute-force technical push, is what unlocked the field. The GABA-B Heterodimer Was Hiding in Plain Sight Dr. Marshall's team at GSK cloned GABA-B1, tried to get it to signal, and couldn't. A screen run to find an intracellular scaffolding partner pulled up something unexpected: a second GABA-B receptor. The moment baclofen activated ion channels in Xenopus oocytes expressing both — with Dr. Marshall in the room — a new category of GPCR biology opened, with heterodimers as obligate signaling units. The Ligand That Wasn't the Ligand Screening orphan receptors in yeast, the team chased peptide hits that made no SAR sense. The realization — triggered by Andrew Brown sitting with a table of actives and inactives — was that the active condition was the acetate buffer, not the peptide. The orphan was a free fatty acid receptor. Years of assumed peptide biology dissolved into a simpler truth hidden in the solvent. Structures Reveal Pockets the Field Didn't Know Existed Once GPCR structures became routine, unexpected binding sites emerged: extra-helical pockets on the glucagon receptor, intracellular sites for C5a antagonists, allosteric modulators bound far outside canonical regions. These discoveries rewrote what counts as "druggable" on receptors once considered fully mapped. Biased Agonism Needs Human Biology, Not Just Pathway Dials The promise of biased ligands — pulling one signaling arm while sparing another — only survives translation if the coupling profile in the relevant human cells matches the cell-line model. Dr. Marshall's caution is hard-won: many animal-model-validated GPCR drugs have failed in the clinic precisely because this step was skipped. Oncology Ignored GPCRs for Decades — and Is Paying Attention Now Twenty years ago, cancer biologists dismissed GPCRs: they weren't oncogenic and didn't kill tumor cells directly. The shift came through the tumor microenvironment — immune cells, chemokine receptors, adenosine signaling — where GPCRs now sit at the center of immuno-oncology strategies that tumor-intrinsic target lists missed. Thirty Years, and the Same Names Keep the Mic One of Dr. Marshall's most pointed observations: the people speaking at GPCR conferences today are, in large part, the people who were speaking at them twenty-five years ago. She frames this as a scientific problem — a narrowing of perspectives on hard problems — not only a social one, and argues the old guard should actively make room for the next cohort. Episode Timeline Timestamps were generated using AI for readability. 00:00 Welcome and guest introduction 02:32 How an undergraduate lecture on β-adrenergic signaling set a career in motion 07:07 A venture capital visit to the LMB and the founding of Heptares 11:28 Building a membrane protein team from scratch 15:29 Unexpected allosteric pockets and the next wave of GPCR drug design 18:47 Which GPCR families pharma is chasing now — and why 21:23 Why animal model validation keeps breaking in clinical trials 27:33 How oncology finally stopped ignoring GPCRs 36:39 The GABA-B heterodimer — the moment baclofen finally worked 40:06 The acetate-in-the-buffer discovery 41:47 Thirty years in, and the same speakers keep getting the mic Selected Quotes "We did the classic experiment in Xenopus oocytes, where you inject the cDNA of both the receptors together. And I was in the room when we then added on baclofen, the agonist, and we could see the ion channel activation." "He just sat down with a table of what was active or inactive. And then he realized the peptides that had been dissolved in acetic acid or acetate were the ones that were active... So it turned out that the ligands were not the peptides at all." "Having worked in GPCRs for 30 years and I look at the conferences, the same people are speaking now as was speaking 25 years ago. So can we now try and encourage the next cohort of people to be the main speakers at conferences?" "We had this really cool room where you could see — you put on 3D glasses and see the receptor in three dimensions sort of floating in the room and moving around." About this episode Fiona Marshall got fascinated with GPCRs after attending a lecture on how the beta-adrenergic receptor in the heart is activated by adrenaline, during her undergraduate studies at Bath University. She then pursued her Ph.D. in neuroscience at Cambridge University. An expert in GPCR biology, Fiona published the first description of the cloning and structural requirements of the GABAB receptor. One of her career path-defining moments came when she visited Dr. Chris Tate and Dr. Richard Henderson at the Laboratory of Molecular Biology in Cambridge, UK. As a co-founder of Heptares Therapeutics , now called Sosei Heptares , a GPCR-focused drug discovery and development biotechnology company, Fiona and her team made considerable breakthroughs in the field of GPCR stabilization and structure-based drug design. Today, Dr. Marshall is the VP Head of Neuroscience Discovery and Head of Discovery UK, Global Head of Neuroscience discovery research leading teams in West Point, Boston, and London at MSD. Join me and learn more about her fascinating career trajectory. Dr. Fiona Marshall on the web LinkedIn Twitter Google Scholar MSD UK Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

How GPCR genetic variants shape psychiatric drug response - Hauser on pharmacogenomics, the iPSYCH biobank, and precision psychiatry at population scale. << Back to podcast list Strategic Partner(s) Alexander Hauser: GPCR Pharmacogenomics and Precision Psychiatry GPCR drug targets carry genetic variation that is far more widespread across human populations than the field has historically appreciated. Hauser's research program asks a pointed question: if a patient fails to respond to a psychiatric drug, or experiences an adverse reaction, is there a GPCR variant in their genome that explains it - and can we find it systematically? To answer this, his work integrates GPCR molecular pharmacology with computational biology, population genetics, and pharmacoepidemiology, drawing on Denmark's iPSYCH biobank - a cohort of 100,000 genotyped psychiatric patients linked to national prescription registries. In parallel, his earlier work on orphan receptor deorphanization used co-evolution analysis and machine learning to generate candidate peptide ligands for putative peptide-binding orphan GPCRs, producing a library of 218 synthetic peptides and yielding the first confirmed hits. Together, these projects represent a rare attempt to connect the molecular detail of receptor pharmacology with the population-scale reality of how those receptors behave in living patients. For Hauser, the stakes are personal: precision psychiatry only matters if it eventually changes what a clinician prescribes. About the Guest Alexander Hauser is a postdoctoral researcher at the University of Copenhagen's Department of Drug Design and Pharmacology, with a part-time affiliation at the Institute for Biological Psychiatry. His research integrates GPCR molecular pharmacology, computational biology, and pharmacoepidemiology to study how human genetic variation in GPCR drug targets shapes drug response and disease risk at a population scale. He completed his PhD under David Gloriam in Copenhagen and an external stay at the MRC Laboratory of Molecular Biology in Cambridge with Madan Babu. His work spans structural analysis, machine learning, population genetics, and the clinical translation challenges that come with precision medicine. Scientific Themes of the Conversation The prevalence and functional consequences of GPCR genetic variants across human populations Co-evolution and machine learning as a framework for orphan receptor deorphanization Denmark's iPSYCH biobank as a unique resource for population-scale GPCR pharmacogenomics The epistemological limits of computational pharmacology without domain knowledge The translational gap between pharmacogenomics findings and clinical prescription practice Interdisciplinary collaboration as a scientific strategy - and its structural requirements Key Insights from the Conversation 1. GPCR variants are not rare edge cases - they are widespread and consequential The prevailing assumption that human GPCR sequences are largely conserved does not hold at a population scale. Hauser's work identified that variants are continuously arising across GPCR drug targets and likely contribute to adverse drug reactions through several distinct mechanisms. This has direct implications for how drug safety is assessed and how clinical trials are designed. 2. Orphan receptors can be systematically approached through evolutionary logic Rather than screening compound libraries blindly against orphan GPCRs, Hauser designed a ligand library by learning the structural and evolutionary logic of known peptide hormone - receptor pairings. The result was 218 candidate peptides, several of which produced confirmed hits in cell-based assays. The approach treats the evolutionary record as a pharmacological hypothesis generator. 3. Denmark's registry infrastructure makes a fundamentally different kind of science possible Most biobanks require active consent and recruit selected populations that do not represent a country's full demographic range. Denmark's CPR number system links psychiatric diagnoses, prescription histories, genotypes, and demographic data across 100,000 patients - without recruitment bias. This allows Hauser to study GPCR variant effects in the context of real prescribing decisions, not controlled cohorts. 4. Computational skill without pharmacological domain knowledge produces noise, not insight Hauser draws a sharp distinction between the ability to manipulate large datasets and the ability to interpret them. Knowing how a dataset was generated - what assay conditions, what cell lines, what confounders - is not optional context. It determines whether a computational finding is meaningful or meaningless. This is the argument for keeping computational pharmacologists embedded in pharmacological communities. 5. Translating pharmacogenomics to clinical practice requires clinical co-design from the start Publishing a finding that GPCR variants predict drug response is not the same as changing a prescription. Hauser is direct about the gap: clinicians need to have shaped the question, not just received the answer. Research that bypasses clinical input tends to stay in the research community. The patient impact requires the clinician's voice in the design phase. 6. The breadth of a scientific career is sometimes a temperament, not a strategy Hauser traces his integrative approach - bridging structural biology, evolutionary data, genetics, and psychiatry - back to a flexible undergraduate program and a deliberate resistance to early specialization. The same quality that led him to a working visa year in Australia before university is the quality that now lets him move across disciplinary boundaries without losing his footing in any of them. Episode Timeline Timestamps are AI-generated from the transcript and should be verified against the final edited audio before publication. 00:00 - Introduction and ecosystem announcements 01:33 - Hauser introduces himself - GPCRs, pharmacogenomics, and precision psychiatry 06:47 - Denmark's iPSYCH biobank and what makes nationwide registry data unique 09:15 - GDPR, unconsented patient data, and the ethics of population-scale research 10:14 - Origin story - hospital internship, Australia, and the decision to pursue science 13:06 - First exposure to computational chemistry - a rotation in Hyderabad 16:04 - Joining David Gloriam's group and first encounter with GPCRs 17:14 - What a computational GPCR scientist actually does across a typical week 20:51 - Having children during a PhD - why Denmark's culture makes it structurally possible 31:45 - Mentoring philosophy - teaching through mistakes and sustaining relationships after departure 37:19 - Networking, collaboration, and the danger of doing science in a bubble 44:18 - Building toward an independent group - precision psychiatry as the research anchor 46:06 - The translational challenge - convincing clinicians to act on pharmacogenomics findings 50:02 - Advice to junior scientists considering a GPCR or computational career 52:44 - Eureka moment - first hits from 218 peptides screened against orphan receptors Selected Quotes "I'm trying to stay in the GPCR field while trying to bring in new methods from other fields and expanding on the clinical implementation and investigation as much as possible." "It's not enough to just be able to manipulate datasets. You really need to also combine it with domain knowledge. Otherwise it's just numbers and labels - and it becomes very quickly very meaningless." "It's important to have clinicians on board very early on. Because otherwise you just throw another paper out there, but it doesn't get traction - it stays in the community. If your ambition is that it has an impact on the patient, then you have to work with the people who are eventually using that information." "Every new result leads you to be more hopeful or to be happier about the outcome. In science you always have to be skeptical about your results. So every time you have your results, you're less skeptical - and that can make you happy." About Dr. Alexander S. Hauser Alexander is currently a postdoc as a member of the personalized medicine cluster in Copenhagen and at the Institute of Biological Psychiatry in Roskilde working with the UK Biobank and other large-scale population cohorts. Alexander has a big interest in the integration of large biomedical data in genomics, structural biology, pharmacology, and pharmacoepidemiology with innovative computational methods to gain novel insights into receptor biology. During his Ph.D. with David Gloriam at the Department of Drug Design and Pharmacology in Copenhagen, he worked on novel analytical methods to identify human signaling systems and thereby discovered endogenous peptides activating several orphan receptors. Alexander had a research sabbatical with Madan Babu at the MRC Laboratory of Molecular Biology in Cambridge, UK, where he was working on the impact of genetic variations on drug response. He received the “HC Ørsted Research talent prize” and “Bayer Pharmaceuticals Ph.D. Award” for his work on GPCRs. Dr. Alexander S. Hauser on the web Twitter ResearchGate University of Copenhagen LinkedIn Google Scholar Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

A conversation with Dr. Joseph Kim exploring GPCR structural biology, cryo-electron microscopy, opioid receptor pharmacology, and the challenges of discovering ligands for understudied receptors like the galanin receptor family. << Back to podcast list Strategic Partner(s) Joseph Kim: Structural Biology and Drug Discovery at GPCRs Scientific Abstract G protein-coupled receptors (GPCRs) remain one of the most important classes of drug targets in modern pharmacology. In this conversation, Dr. Joseph Kim discusses the intersection of structural biology, membrane protein biochemistry, and drug discovery through the lens of GPCR research. Dr. Kim, a postdoctoral scholar in the laboratory of Dr. Aashish Manglik at the University of California, San Francisco, studies GPCR structure using cryo-electron microscopy. His work focuses on understanding how ligands interact with receptors such as the μ-opioid and κ-opioid receptors, and how structural insights can guide the development of new pharmacological modulators. The discussion explores how structural biology technologies—particularly cryo-EM—have transformed the ability to visualize receptor-ligand interactions and uncover the molecular mechanisms underlying receptor signaling. Dr. Kim also reflects on the conceptual challenges of studying membrane proteins, the value of pursuing difficult scientific problems, and how curiosity about drug mechanisms led him toward GPCR pharmacology. Listeners will gain insight into the scientific reasoning behind GPCR structural studies, the evolving toolkit used to interrogate receptor activation, and the broader landscape of receptor-based drug discovery. About the Guest Dr. Joseph Kim is a structural biologist studying membrane proteins and GPCR pharmacology. He is currently a postdoctoral scholar in the laboratory of Dr. Ashish Manglik at the University of California, San Francisco, where he uses cryo-electron microscopy to investigate ligand binding and receptor conformations. Dr. Kim’s research focuses on druggable membrane proteins, particularly GPCRs involved in neurological signaling such as opioid receptors and the galanin receptor family. His work combines structural biology, membrane protein biochemistry, and pharmacological insights to better understand how ligands modulate receptor signaling. His broader scientific interests lie at the interface of structural biology and drug discovery, where molecular structures inform the design and development of new therapeutics. Scientific Themes of the Conversation Structural biology of GPCR–ligand interactions Cryo-electron microscopy in membrane protein research GPCR pharmacology and drug discovery strategies Opioid receptor structure and ligand modulation Challenges in targeting peptide-binding GPCRs Exploring understudied receptors such as the galanin receptor family Key Insights from the Conversation 1. Difficult Scientific Problems Often Drive Discovery Dr. Kim describes a personal inclination toward challenging research areas. Membrane proteins—historically difficult to purify and structurally characterize—represent precisely the kind of problems that attract scientists interested in pushing methodological boundaries. 2. Structural Biology Reveals the Molecular Logic of Drug Action Through cryo-EM studies of the μ- and κ-opioid receptors, Dr. Kim explains how visualizing receptor-ligand complexes provides direct insight into how small molecules stabilize specific receptor states and produce pharmacological effects. 3. GPCR Drug Discovery Is Increasingly Structural Modern GPCR drug discovery increasingly integrates structural data, computational docking, and pharmacology. Structural snapshots of receptor-ligand complexes can validate docking predictions and guide medicinal chemistry. 4. Polypharmacology Is a Central Challenge One small molecule studied by Dr. Kim’s group interacts with multiple opioid receptors, acting as an antagonist at one receptor and an inverse agonist at another. This illustrates how receptor pharmacology often involves complex, receptor-specific effects. 5. Many GPCRs Remain Poorly Understood The galanin receptor family represents an example of GPCRs with important physiological roles but limited pharmacological tools. The lack of potent small-molecule ligands continues to hinder research into these receptors. 6. New Tools Enable Re-exploring Old Questions Advances in cryo-EM, computational modeling, and machine learning are enabling scientists to revisit receptors that were previously considered difficult to drug. 7. Scientific Environments Matter Dr. Kim emphasizes the importance of research environments that allow curiosity, experimentation, and even failure. Supportive collaborative environments accelerate scientific progress. Episode Timeline 00:00 — Introduction Introduction to Dr. Joseph Kim and his current position at UCSF. 01:00 — Early curiosity about drugs and poisons How childhood curiosity about toxic plants led to an interest in drug research. 05:00 — Choosing science over medicine Transition from a pre-medical track to pursuing scientific research. 07:00 — Discovering cryo-electron microscopy Graduate training in cryo-EM and early exposure to membrane protein structural biology. 10:00 — Pursuing challenging scientific problems Why difficult fields like membrane protein structural biology can be particularly appealing. 18:00 — Choosing a postdoctoral lab Criteria used to identify the right postdoctoral environment. 23:00 — The scientific appeal of membrane proteins How membrane proteins serve as the entry point for signaling molecules. 29:00 — Structural studies of opioid receptors Dr. Kim describes solving structures of μ- and κ-opioid receptors bound to small-molecule ligands. 34:00 — The galanin receptor: an understudied GPCR Why the galanin receptor family presents intriguing scientific questions. 45:00 — Scientific turning points Three key “aha moments” that shaped Dr. Kim’s scientific trajectory. 52:00 — Advice for young scientists The importance of curiosity, persistence, and choosing supportive research environments. Selected Quotes “The line between drugs and poisons is not so different.” “If someone tells me something is difficult, I tend to run toward it rather than away from it.” “Membrane proteins are where signaling begins—the moment a molecule tells the cell what to do.” “It’s perfectly fine to feel fear when entering a new field, but it shouldn’t stop you from pursuing the questions that excite you.” Full Transcript (Formatted for readability. Minor transcription artifacts removed while preserving scientific meaning.) Dr. Yamina Berchiche: Hello, everyone. This is Yamina from Dr. GPCR. I'm very excited to be recording this particular podcast episode. Joe reached out to me on LinkedIn, and we started a fantastic conversation, and I'm excited to bring you, Joe, to the podcast today. Joe Kim, welcome to the Dr. GPCR podcast. Dr. Joseph Kim: Thank you, Yamina. It's an absolute pleasure to be here. Dr. Yamina Berchiche: Very excited to have you on. Maybe we can start by you introducing yourself to the audience. Dr. Joseph Kim: My name is Joseph Kim. I go by Joe. I am currently a postdoctoral scholar in Professor Ashish Manglik’s lab here at the University of California, San Francisco. Dr. Yamina Berchiche: Wonderful. I’m going to put it out there on the record—I’ve been reaching out to Ashish. We're going to have to push him towards coming onto the podcast. I listened to one of his talks at a Gordon Conference and he was phenomenal. Ashish, if you’re listening to this—we want you on the podcast. So Joe, tell me a little bit about how you ended up working on GPCRs in Ashish’s lab. I’m really curious about your career trajectory. Dr. Joseph Kim: Sure. When it comes to how I got involved in GPCRs, I guess I can start from when I was a kid. I grew up in Corvallis, Oregon, which is a college town about 90 miles south of Portland. There were a lot of trees and outdoor flora and fauna around me. I spent a lot of time exploring and going to the library. One day I found a book about poisonous plants—essentially explaining which berries you could eat and which you absolutely shouldn’t. That’s probably where my interest in drugs and toxins began. There’s that saying that the difference between drugs and poisons is often just the dose. That fascination stuck with me. Later, during my final year of graduate school at UW–Madison, I was thinking about postdoctoral positions and reading papers about drug discovery. I remember distinctly sitting back one day and thinking: “Ah crud… I’m going to have to study GPCRs, aren’t I?” And that realization eventually led me to Ashish’s lab. Dr. Yamina Berchiche: How did you initially decide to pursue science? Dr. Joseph Kim: I was always interested in science growing up, especially health sciences. When I started college at Oregon State University, I entered as a pre-med student. But I realized something about myself—I would spend too much time asking why certain treatments were prescribed. That constant questioning felt more aligned with being a scientist than being a physician. Dr. Yamina Berchiche: You mentioned earlier that the project you worked on involved the μ-opioid receptor and the κ-opioid receptor with a small molecule that showed interesting pharmacology. What happened to that project? Was it eventually published? Dr. Joseph Kim: Yes, it was published this year in ACS Central Science . Dr. Yamina Berchiche: Congratulations—that’s wonderful. All right, I always ask this question from everyone who comes on the podcast. What is your favorite GPCR? Dr. Joseph Kim: People will probably assume that it’s one of the opioid receptors, but I’m actually going to surprise them. My favorite GPCR is not the opioid receptors. Instead, it’s the galanin receptor . Dr. Yamina Berchiche: The galanin receptor? I’m not very familiar with that one. Dr. Joseph Kim: Exactly—and that’s part of why I find it so fascinating. There are three members of the galanin receptor family: galanin receptor 1, 2, and 3. The one I’m most interested in is galanin receptor 1 . It’s highly expressed in the brain and spinal cord. There’s evidence suggesting that it plays roles in feeding behavior and analgesia , somewhat similar to opioid receptors. Some studies also suggest that the galanin receptors may interact with the μ-opioid receptor. In fact, some groups believe there may even be dimeric interactions between the receptors. But the major challenge is that no one has identified a potent small-molecule ligand for these receptors. Dr. Yamina Berchiche: That’s fascinating. Dr. Joseph Kim: Recently, structures of galanin receptors bound to their endogenous peptide ligand—galanin—were published. Those structures revealed something really unusual: the peptide binds laterally within the receptor. That unusual binding mode might explain why it has been so difficult to identify small-molecule ligands. Dr. Yamina Berchiche: That makes sense. Whenever I hear about peptide-binding GPCRs with buried or hydrophobic binding pockets, I immediately think: good luck finding small molecules. Dr. Joseph Kim: Exactly. The endogenous peptide is buried laterally within the receptor, which means an exogenous small molecule might have difficulty accessing that pocket. Dr. Yamina Berchiche: Unless you start thinking about allosteric modulators. Dr. Joseph Kim: Right—and once you start thinking about allosteric modulation, you open an entirely new set of questions. Dr. Yamina Berchiche: Absolutely. Especially when you consider that the galanin system involves three receptors and potentially different signaling pathways. I just looked it up while we were talking. It appears galanin has roles in nociception, depression, and sleep . That’s a complicated pharmacological landscape. Dr. Joseph Kim: It is. You could easily imagine separate therapeutic programs targeting those different physiological effects. And of course, that also means the pharmacology becomes much more complex. Dr. Yamina Berchiche: So how did you first encounter the galanin receptor? Dr. Joseph Kim: It actually came from discussions with Ashish when I first joined the lab. I told him I was interested in three things:• structural biology• drug discovery• neurological systems The galanin receptor fit all three of those interests. So Ashish introduced it as a potential project area, and it stuck with me. Dr. Yamina Berchiche: What kinds of questions are you hoping to answer about that receptor family? Dr. Joseph Kim: At a very basic level, one of the key questions is simply: Can we identify a small molecule that modulates the galanin receptor? In the early 2000s there were screening campaigns against these receptors, but nothing promising emerged. So the question becomes: Did we simply not search deeply enough?Or were the screening strategies themselves limited? With today’s tools—computational docking, structural biology, and machine learning—we might be able to revisit those questions in a more sophisticated way. Dr. Yamina Berchiche: I completely agree. We now have tools that simply didn’t exist ten or twenty years ago. That means receptors that were previously considered difficult or unproductive targets might be worth revisiting. But I also think we need to use these tools carefully. Dr. Joseph Kim: Yes, exactly. One of the risks with new technologies is that people sometimes build the research question around the tool rather than using the tool to answer the question. We need to integrate these tools thoughtfully rather than simply following the excitement. Dr. Yamina Berchiche: I agree. There are really two complementary directions in GPCR research. One direction is to develop new tools using well-characterized receptors—the ones we understand well enough to validate new methods. The other direction is to apply those tools to the more challenging or understudied receptors. Dr. Joseph Kim: Exactly. You need a solid foundation. If the receptor system and the tool are both unknowns, it becomes very difficult to interpret the results. Dr. Yamina Berchiche: That’s a great point. Let’s shift gears a little bit. Looking back at your career so far, what would you say are the three biggest “aha moments” that shaped your trajectory as a scientist? Dr. Joseph Kim: The first one was definitely the moment I described earlier—when I was sitting there reading papers and suddenly realized: “I’m going to have to study GPCRs.” That was a turning point. The second “aha moment” came when I solved the structures of the μ-opioid and κ-opioid receptors bound to the candidate small molecule we were studying. Showing those structures to my colleagues—and realizing that the experiment actually worked—was incredibly satisfying. It also helped me overcome the fear I had about transitioning into membrane protein structural biology. The third “aha moment” happened much earlier, when I switched from the pre-med track to pursuing graduate school. One of my close friends at the time noticed how quickly I pivoted once I realized that medicine wasn’t the right path for me. That moment clarified that research was the direction where I really belonged. Dr. Yamina Berchiche: That’s a beautiful chronological sequence. If we think about your future—have you started thinking about what comes after your postdoctoral work? Dr. Joseph Kim: Yes, I have. I would like to remain in drug discovery , ideally working on GPCRs if possible. I can imagine myself in a biotech or pharmaceutical environment where I’m helping guide drug development programs—evaluating data from different teams and deciding whether a candidate molecule should move forward. That might involve integrating information from pharmacology, toxicology, manufacturing, and preclinical research. Essentially serving as a bridge between the science and the development process. Dr. Yamina Berchiche: That sounds like an exciting direction. And finally, what advice would you give to young scientists who want to enter the GPCR field? Dr. Joseph Kim: The first piece of advice is don’t let fear stop you . It’s completely normal to feel intimidated when entering a complex field like GPCR biology. But that fear shouldn’t prevent you from pursuing ideas that excite you. The second piece of advice is to find an environment where you are allowed to learn from mistakes. The reason I was able to transition successfully into GPCR structural biology was because I joined a lab where people were supportive and willing to teach. Being in that kind of environment makes a huge difference. Dr. Yamina Berchiche: I completely agree. The worst thing you can do in science is nothing. Taking action—even if it leads to mistakes—helps you learn and move forward. Joe, thank you so much for joining the podcast today. I really enjoyed our conversation. Dr. Joseph Kim: Thank you, Yamina. It’s been an absolute pleasure. Dr. Yamina Berchiche: Thank you. Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Dr. Terry Hebert explains why studying GPCRs in HEK293 cells misses critical biology — and how iPSC-derived models and intracellular receptor targeting are reshaping drug discover << Back to podcast list Strategic Partner(s) Terry Hebert: How Cellular Background and Localization Influence GPCR Function Scientific Abstract Most of what we know about GPCR signaling was learned in HEK293 cells — a system that reveals what is possible but not necessarily what is happening. This conversation with Dr. Terry Hebert confronts that gap directly. Dr. Hebert's research focuses on the angiotensin AT1 receptor, a signaling hub coupled to Gq, Gi, G12, and beta-arrestin simultaneously — far exceeding the simple binary framework that guided a biased agonist into a failed clinical trial. His lab develops BRET- and FRET-based biosensors that produce different conformational outputs depending on the cell type, and is now deploying them in iPSC-derived cardiomyocytes and patient-specific stem cell models. The discussion also explores GPCRs beyond the cell surface — including caged ligands designed to drug receptors on the nuclear membrane, and the unexpected discovery that G-proteins may act as transcriptional regulators. For Dr. Hebert, three decades in the wrong cellular background was reason enough to start over. About the Guest Dr. Terry Hebert is a Professor of Pharmacology and Therapeutics at McGill University. His research centers on GPCR signaling networks, biosensor development, and the role of cellular context in receptor pharmacology. Trained in microbiology and ion channel biology at the University of Toronto, he transitioned to GPCRs during his postdoctoral work with Michel Bouvier. His lab develops resonance energy transfer-based biosensors and applies them in induced pluripotent stem cells to study receptor function in physiologically relevant settings. His contributions span GPCR dimerization, nuclear receptor signaling, and the emerging role of G-proteins as transcriptional regulators. Scientific Themes of the Conversation Cellular Context as the Missing Variable — Why receptor pharmacology measured in HEK293 cells may not reflect what happens in native tissues, and how biosensors reveal cell-type-dependent signaling outputs. Beyond the Gq/Beta-Arrestin Dichotomy — The AT1 receptor couples to Gq, Gi, G12, and beta-arrestin simultaneously, and the clinical failure of a biased agonist exposed the cost of oversimplifying that signaling landscape. iPSC-Derived Models for GPCR Drug Discovery — Using induced pluripotent stem cells differentiated into cardiomyocytes, fibroblasts, and patient-specific cell types to study receptor signaling in disease-relevant backgrounds. Intracellular GPCRs as Drug Targets — Receptors on the nuclear and mitochondrial membranes represent an untapped pharmacological frontier, and caged ligands offer a route to drugging them selectively. G-Proteins as Transcriptional Regulators — The observation that G-proteins enter the nucleus and interact with transcriptional machinery, suggesting functions entirely distinct from canonical cell-surface signaling. Navigating Serendipity and Risk in Discovery — From the accidental observation of GPCR dimers to negative controls gone wrong, the role of openness to unexpected results in shaping a research program. Key Insights from the Conversation 1. HEK Cells Show What's Possible, Not What's Happening Dr. Hebert's biosensors produce different conformational outputs when expressed in HEK293 cells versus vascular smooth muscle cells, even when challenged with the same ligand. The implication is that cellular context fundamentally shapes receptor behavior — and most of the field's pharmacological maps were drawn in the wrong terrain. 2. The AT1 Receptor Defies Simple Classification The angiotensin AT1 receptor is not just a Gq-coupled receptor with a beta-arrestin side story. It couples to Gi, G12, and likely additional pathways. Dr. Hebert describes it as an interaction hub wired into networks whose full scope remains unknown — a receptor whose complexity scales with every new cell type examined. 3. A Clinical Trial Failure That Pointed Forward The Trevena biased agonist for the AT1 receptor failed in clinical trials, meeting none of its primary endpoints. Dr. Hebert argues this was not a failure of the concept but of incomplete pharmacological characterization — the ligand activated more pathways than assumed. He views it as a starting point, not an ending. 4. Knocking Out G-Proteins Reveals Cellular Rewiring When individual G-proteins are knocked out in HEK293 cells, the cells rewire their signaling networks to compensate. This means the knockout cell is intrinsically different from the wild-type — complicating any conclusions drawn from loss-of-function experiments in immortalized lines. 5. Patient-Derived iPSCs Open the Door to Personalized GPCR Pharmacology Dr. Hebert's lab is transitioning to iPSC-derived cardiomyocytes and fibroblasts, including cells from patients with cardiomyopathies. The goal is to test therapeutic strategies targeting the AT1R, alpha-adrenergic, and beta-adrenergic systems in individual patient contexts before clinical intervention. 6. Drugging GPCRs on the Nuclear Membrane GPCRs are not confined to the cell surface. Dr. Hebert's lab developed caged ligands that cross the plasma membrane and are uncaged intracellularly, enabling selective activation of receptors on the nuclear membrane — a moment he describes as one of the most exciting in his career. 7. Discovery Requires Being Open to Being Wrong Dr. Hebert's advice to young scientists: embrace the complexity that intimidates your mentors. His own career was shaped by serendipitous observations — GPCR dimers that no one expected, negative controls that turned out to be discoveries. The pattern is consistent: the most important findings came from results that initially looked like mistakes. Episode Timeline Timestamps were generated using AI for readability. 00:00 Introduction 01:49 From microbiology to membrane proteins — Dr. Hebert's path to GPCRs 03:26 The angiotensin AT1 receptor — a favorite and a mystery 05:05 Why the Gq/beta-arrestin dichotomy broke down — the Trevena trial and its aftermath 07:15 Cellular context as the elephant in the room — biosensors revealing cell-type-dependent outputs 10:54 Building the toolkit — biosensors, iPSC-derived models, and patient-specific cells 18:44 Industry partnerships and the path from bench to pharma engagement 22:44 Intracellular GPCRs — drugging receptors on the nuclear membrane 26:21 Advice to young scientists — the unexpected result that redirected the project 27:49 Three aha moments that reshaped a career: dimers, nuclear GPCRs, and G-proteins as transcriptional regulators Selected Quotes "A HEK cell really kind of shows what's possible, but it doesn't really show what's happening." — Dr. Terry Hebert "I think what we don't know is how much we don't know." — Dr. Terry Hebert "You have to be open to discovery by being open to kind of being wrong." — Dr. Terry Hebert "The things that they originally came into place for get sampled for many other functions. And some of those functions get conserved and some get further modified to serve completely different roles than what we're used to thinking." — Dr. Terry Hebert About this episode Dr. Terry Hébert wanted to be a microbiologist. Instead, he ended up getting interested in membrane protein as he followed the biology of a bacterial toxin that affects a mammalian ion channel. Today he and his team are working on understanding receptor signaling in specialized cellular environments to gain a better grasp of receptor function in pathophysiological settings with a special interest in the cardiovascular system. His favorite GPCR is the angiotensin 1 receptor, especially for its ability to activate a large variety of signaling pathways. Terry is also very active on social media. With over 2000 followers on Facebook and Twitter, he shares the latest available information on GPCR research daily. Dr. Terry Hébert on the web Institute of Health Sciences Education Hébert Lab LinkedIn Facebook GPCR Consortium PubMed Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Paul J. Gasser About Dr. Paul J. Gasser " I received my BS and MS in Zoology & Physiology at the University of Wyoming, where I studied signaling processes involved in light-induced regulation of melatonin synthesis in the rainbow trout pineal organ, a directly photosensitive endocrine organ. I received my PhD in Biology at Arizona State University, where I worked in the lab of Miles Orchinik, studying cellular mechanisms underlying non-genomic actions of corticosteroid hormones. My postdoctoral work, conducted at the University of Bristol, UK, in Christopher Lowry's lab, examined the role of organic cation transporter 3 (OCT3) in the regulation of monoamine signaling in the brain. I joined the faculty of Biomedical Sciences at Marquette in 2007. I teach undergraduate Biochemistry and a variety of graduate neuroscience courses. Research in my lab is currently focused on understanding the signal transduction pathways activated by beta-adrenergic receptors localized to the inner nuclear membrane and their role in the regulation of gene expression." Dr. Paul J. Gasser on the web Gasser Lab Marquette University Google Scholar ResearchGate LinkedIn Twitter Dr. GPCR Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Chloe Hicks About Chloe Hicks Chloe Hicks will graduate from Duke University this spring with a B.S degree in Biology with a concentration in Pharmacology. She has been an undergraduate student member in the Rajagopal Lab since January 2021 and has contributed to multiple projects exploring the underlying mechanisms of biased signaling at chemokine receptor 3 (CXCR3). These previous endeavors involved exploring the effect of subcellular location on the signaling profile of CXCR3’s three endogenous biased ligands, elucidating the role of site-specific receptor phosphorylation in the differential signaling outputs of biased agonists, and demonstrating the ligand specificity behind GRK recruitment to endosomes upon receptor internalization. She is currently working on her senior thesis which involves identifying the non-canonical signaling effectors involved in the activation of Atypical Chemokine Receptor 3 (ACKR3), a receptor which does not couple to G protein and has been shown to maintain its activation in the absence of β-arrestin. Chloe Hicks on the web ORCID LinkedIn Dr. GPCR Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Exploring Career Paths in GPCR Research with Dr. Jacek Mokrosiński About Dr. Jacek Mokrosiński "Jacek is a Senior Scientist at Novo Nordisk specializing in molecular pharmacology and cell-based screening technologies. He works in a multidisciplinary Chemical Biology team based at the recently established US R&D hub in Lexington, MA. Originally from Łódź, Poland, Jacek completed his Master's degree in Biology, specializing in Biochemistry at the University of Łódź. He then moved to Denmark, where he trained at the University of Copenhagen under supervision of Professor Thue W. Schwartz, and worked closely with Dr Birgitte Holst studying structural and mechanistic properties of ghrelin receptor and GPCRs involved in regulation of metabolism. After completing his Ph.D., he pursued research in genetics of metabolic regulation at the Institute of Metabolic Science - Metabolic Research Laboratories at the University of Cambridge in the team led by Professor I. Sadaf Farooqi. His research aimed at understanding molecular mechanism through which rare genetic variation may lead to or protecting from excessive body weight gain. As part of Farooqi's team, he characterized a series of novel human genetic variants identified in several GPCRs associated with obesity and other metabolic diseases, including GPR10, Melanocortin 4, Serotonin 2C and TRH receptors. Since 2021, Jacek has been working at Novo Nordisk at its research sites in the UK (Oxford) and the US (Indianapolis, Indiana and most recently Lexington, Massachusetts). He is passionate about cell-based in vitro technologies to study mechanistic properties of GPCRs and understanding the dynamics of receptor signalling. He is an avid proponent of close collaboration between industry and academia." Dr. Jacek Mokrosiński on the web ORCID ResearchGate LinkedIn Twitter Dr. GPCR AI Summary AI-generated content may be inaccurate or misleading. Always check for accuracy. Quick Recap Yamina and Jacek discussed their experiences with name mispronunciations, cultural differences, and the importance of a multidisciplinary approach in drug development. They also shared their career journeys, emphasizing the value of being open-minded, proactive, and embracing new opportunities. Lastly, they discussed their research interests, particularly in the field of GPCR, and the importance of method development, integrity, and honesty in scientific research. Next Steps Jacek will collaborate with Alex Romeo on a podcast about transitioning to the industry. In future talks and interviews, Jacek will share his stories and advice about GPCRs. Yamina will schedule a future talk with Jacek about GPCRs as therapeutic modalities. Summary Embracing Cultural Differences and Collaboration Yamina and Jacek shared their experiences with name mispronunciations and variations and discussed the importance of embracing cultural differences. They also discussed their professional backgrounds, highlighting the benefits of a multidisciplinary approach in drug development and the importance of collaboration between academia and industry. They talked about their shared passion for advancing science and improving patient outcomes, and their early interests in science and chemistry. They also shared their appreciation for documentaries showcasing manufacturing processes and the value of true experimentation in scientific research. Jacek's Career Journey and Advice Jacek and Yamina discussed Jacek's career journey, focusing on his experiences, challenges, and lessons learned. Jacek highlighted the importance of being open-minded and proactive, emphasizing that he learned by doing rather than taking specific courses. He also underscored the role of the people around him, expressing gratitude for their guidance and support. His advice was to be ready for changes and to embrace opportunities as they arise. Jacek's career path, which led him from Poland to Denmark and then to the US, exemplified his advice in action. Passion for Science and Career Journeys Yamina and Jacek discussed their passion for science and how it led them to their current careers. Jacek shared his experience of working with Piketa and how he found a job in Seda's lab at Cambridge, where he could immediately contribute due to his technical skills. Yamina agreed with Jacek's sentiments and spoke about her own journey, expressing her happiness in discussing science and reading papers. They emphasized the importance of finding a job that aligns with one's interests and strengths and being open to opportunities. They also highlighted the need for a work-life balance and the joy of a well-done job. Embracing Networking for Professional Growth Jacek and Yamina discussed the importance of building a network and being open to new opportunities. Jacek realized that being introverted doesn't mean he can't benefit from networking and interaction with others. He also highlighted the benefits of attending conferences and engaging with colleagues, sharing examples of how such interactions led to collaborations and new opportunities. Yamina agreed, emphasizing the importance of mental preparation and embracing different social situations, both virtual and in-person. They underscored the value of these interactions for professional growth and encouraged others to adopt a proactive approach to networking. Building Professional Connections Strategies Yamina and Jacek discussed the importance of building professional connections and strategies for introducing oneself to potential contacts. They emphasized the need to be mindful of the other person's time, provide clear explanations for the purpose of the connection, and offer something of value in return. They also highlighted the advantages of using LinkedIn as a tool for networking and the significance of personalizing messages to make a lasting impression. GPCR Research Interests and Collaborations Yamina and Jacek had a deep and engaging discussion about their research interests and achievements, particularly in the field of GPCR. Jacek shared his fascination with the growth hormone secretion receptor and the melanocortin 4 receptor, and their roles in regulating body weight and growth. Yamina, in turn, talked about her work on melanocortin receptors and an upcoming collaboration with a postdoc scientist. They also highlighted the importance of method development, integrity, and honesty in scientific research. The discussion revealed their interest in GPCRs as therapeutic modalities and possible future collaborations. Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Yamina Berchiche About this episode In this Episode 0 of the brand new Dr. GPCR podcast , your host and founder, Dr. Yamina Berchiche introduces the very first podcast dedicated to GPCRs researcher and their work. This podcast is part of the Dr. GPCR Ecosystem, with the goal is to bring together GPCR scientists, biotech, and pharma leaders as well as suppliers working on GPCRs by providing opportunities to connect, share, form trusting partnerships, grow, and thrive together to accelerate GPCR drug discovery and improve human health. Dr. Yamina Berchiche on the web - Website - LinkedIn - PubMed - Twitter - Facebook - Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Brian Arey on GPCR drug discovery from the inside - GPR56 mechanotransduction, the KLF2 pathway, organizational patience, and unpublished science. << Back to podcast list Strategic Partner(s) Brian Arey - Part 2: GPCR Drug Discovery and the Science Nobody Publishes Drug discovery in the pharmaceutical industry generates enormous volumes of foundational science that never reaches a journal. Target validation programs are built, defended, and sometimes cancelled before a single paper is submitted. The scientists who do this work accumulate expertise - in receptor signaling, cardiovascular physiology, mechanobiology - that exists in internal reports and institutional memory rather than the published record. In this conversation, Arey traces the full arc of how a pharmaceutical research program is born, resourced, and either advanced or discontinued. He describes his work on GPCR mechanotransduction in endothelial cells - including the early identification of GPR56 as a mechanical sensor and his sustained case for the KLF2 signaling pathway as a GPCR-linked therapeutic target in atherosclerosis - and is candid about what happens when organizational priorities shift and a program you believe in gets shelved. Arey's conviction that the KLF2-GPCR axis in vascular endothelium represents an underexplored route to treating atherosclerosis has not diminished with time. This episode is for scientists who want to understand what early drug discovery actually costs - and what it produces that the literature cannot capture. About the Guest Brian Arey is a pharmacologist and physiologist with over 25 years of pharmaceutical research experience at Bristol-Myers Squibb. His scientific work spans GPCR mechanotransduction in vascular endothelial cells, cardiovascular target validation, thrombosis pharmacology, and metabolic disease biology, with contributions to multiple clinical programs including preclinical models that supported the apixaban development program. He has led mechanistic pharmacology operations and served as interim head of a 70-person cross-functional research organization spanning mechanistic pharmacology, compound management, and core automation. His approach to drug discovery is grounded in classical physiology and driven by a willingness to enter fields - bone biology, thrombosis, endothelial function - with limited prior expertise and build toward the question the science is actually asking. Scientific Themes of the Conversation The architecture of drug discovery: from pathophysiology to program governance GPCR mechanotransduction in endothelial cells: GPR56, KLF2, and atherosclerosis Hypothesis discipline and the "killer experiment" in early discovery Intellectual humility and the dynamics of cross-functional drug discovery teams Career breadth across physiology systems: scientific advantage and professional cost Scientific identity, intuition, and the scientist who refuses the mold Key Insights from the Conversation Early discovery is the most creative and most invisible space in pharmaceutical research Arey describes early-stage drug discovery as structurally similar to academic research - hypothesis-driven, iterative, without guaranteed output. The difference is that the science is consumed by the organization rather than the literature. Scientists who build careers in this space often generate more foundational knowledge than their publication records reflect, and Arey is unusually candid about what that obscurity actually feels like from the inside. The "killer experiment" is the one designed to end your own program A mentor taught Arey the concept of the killer experiment: the definitive test engineered specifically to challenge your own hypothesis before more resources are committed. The discipline requires a willingness to invest in an outcome that might close what you have built. Arey calls this one of the most important and least instinctive skills in pharmaceutical research - and one that most scientists are never explicitly taught. GPR56 as a GPCR mechanosensor in endothelial cells - a decade ahead of the published literature Working on endothelial cell responses to shear stress, Arey identified GPR56 as a candidate mechanosensor before the concept had been established in print. A paper confirming the receptor's mechanotransduction function in endothelial cells appeared roughly ten years later. He describes the experience with something between resignation and dry satisfaction: he knew, the data supported it, and the field eventually arrived. The KLF2-GPCR axis in atherosclerosis: a program that ended, a conviction that did not Arey spent years building the case for GPCRs and the KLF2 transcription factor as a linked anti-inflammatory pathway in vascular disease. The program was eventually deprioritized as oncology absorbed industry attention. His belief in the biology has not changed. He says so directly: "somebody please do it" - not as a rhetorical gesture, but as a genuine ask to whoever is listening. Breadth across physiology systems carries a professional cost that nobody warns you about Moving between neuroscience, reproductive endocrinology, bone biology, thrombosis, and cardiovascular disease in one career generates a depth of cross-system physiological understanding that Arey considers genuinely valuable for drug discovery. He is equally honest that the approach slows career progression - each transition resets the publication clock and delays the depth of specialization that institutional advancement rewards. He made the trade knowingly, and would make it again. In drug discovery, intuition precedes the hypothesis - not the other way around Arey argues that the most significant hypotheses he has generated throughout his career originated in pattern recognition and intuition, before any supporting data existed. He is careful not to overstate this: data drives decisions. But he maintains that the hypothesis itself - the moment where you commit to a direction - comes from something that looks more like a gut feeling than a literature review. For scientists trained to distrust that instinct, it is a useful challenge. Trust is not a leadership style - it is the operating condition for innovative science Running a 70-person research organization, Arey returns repeatedly to trust as the variable that determines whether people bring their actual thinking to the team. Not warmth, not informality - but the concrete belief among scientists that their leader has their interests at heart. He describes this as the only environment in which people are willing to surface the unconventional idea that might be the one that works. Episode Timeline Timestamps are AI-generated from the transcript and may require minor manual adjustment. 01:30 - Returning to the conversation: leading a 70-person organization on an interim basis 03:10 - Leadership style: trust, communication, and creating the conditions for good science 08:58 - The drug discovery process from pathophysiology to target selection 16:49 - Organizational patience and the go/no-go discipline in early discovery 23:09 - GPR56 as a GPCR mechanosensor: knowing the answer before the field did 27:35 - Intellectual humility and the drug discovery team as a problem-solving unit 37:10 - The KLF2 pathway, GPCRs, and atherosclerosis: a program that ended too soon 42:39 - Career breadth across physiology: the advantage and the professional cost 57:50 - Scientific identity, introversion, and putting yourself out there 01:05:19 - Intuition as hypothesis generator: what comes before the data Selected Quotes "There was a paper that came out a couple of years ago on GPR-56, showing that GPR-56 was a mechanotransducer in endothelial cells. And literally, I knew that about 10 years before everybody. That's just the way it goes." "All the key discoveries I've made in my career were based initially on intuition. And then how the puzzle pieces fit together. From there, you use the data to drive whether or not you're correct." "Yeah, it inhibits your career. I will say that." "I've spent 25 years pushing back against that. I feel like as scientists, we should be who we are. Just because I don't act like somebody else doesn't mean I'm not a good scientist. It just means I'm different." About this episode Brian Arey is Senior Director of Mechanistic Pharmacology within Leads Discovery and Optimization at Bristol-Myers Squibb Co . in Lawrenceville, NJ. He obtained both his MS and Ph.D. in Neuroendocrine Physiology at Florida State University before completing his postdoctoral training at Northwestern University. He then moved to work in the pharmaceutical industry where he has held positions of increasing responsibility. He currently leads a team that provides a mechanistic understanding of small molecule drug candidates across the entire portfolio of BMS. Brian has contributed to the discovery or development of 5 marketed drugs through his work spanning molecular, biochemical, cellular, and in vivo assessment of drug candidates in many different physiological systems. Dr. Arey’s laboratory discovered the first described synthetic agonists and antagonists of the FSHR and has been an early champion of signaling bias as a physiological mechanism of gonadotropin action. He continues to pioneer in drug discovery studying GPCRs and other target classes. His recently published book on signaling bias, Biased Signaling in Physiology, Pharmacology, and Therapeutics is available on Amazon . I sat down with Brian to chat about GPCRs, working in the industry, and being a leader. This is part 1 of our conversation. Dr. Brian Arey on the web LinkedIn ResearchGate Pubmed Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

< Back Introduction to GLP-1 pharmacology October 8, 2026 10 AM - 11:30 AM EST 🔒 Watch Recordings - Join Premium Access the full library of recorded Masterclass sessions. Get Live Updates Be notified when new live Masterclasses are scheduled. Coming Soon Upcoming Live Sessions

<< Back to podcast list Strategic Partner(s) GPCR location matters with Dr. Gabriele Kockelkoren About Gabriele Kockelkoren I have a strong background in both physics and molecular biology and, accordingly, I strive in interdisciplinary environments. After completing a cum laude BSc. and MSc. in Nanobiology at the Technical University of Delft in The Netherlands, I pursued a PhD at the University of Copenhagen under the supervision of Prof. Dimitrios Stamou. In my PhD, I studied the nanoscale spatial organization of G protein-coupled receptors (GPCRs) at the plasma membrane of living cells. Importantly, my work revealed heterogeneous spatial patterns of receptor density and activation, that are modulated in a drug-dependent manner. These findings identify nanoscale GPCR spatial organization as an integral element of their activity and signaling. Currently, I am a Postdoctoral Fellow in the lab of Prof. Alice Ting developing programmable receptors for molecular sensing and controlling cellular behaviour. Gabriele Kockelkoren on the web Stanford University X LinkedIn Google Scholar ORCID ResearchGate Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Annette Gilchrist on why native cell systems change GPCR screening, constitutive beta-arrestin activity at FFA2, and the pharmacogenomics gap in drug discovery. << Back to podcast list Strategic Partner(s) Annette Gilchrist: Native Cell Systems, Biased Agonism, and the Pharmacogenomics Gap Biased agonism promised a cleaner path to better drugs - compounds that activate the beneficial arm of a receptor while leaving the harmful one alone. In practice, the picture is far more complicated. Whether a 20% reduction in beta-arrestin coupling matters therapeutically depends on the cell type, the complement of intracellular effectors present, and the receptor's own baseline activity in that tissue. These are questions you cannot answer in a HEK cell overexpressing a receptor it was never meant to see. Annette Gilchrist has built her research program around that premise. Working on chemokine receptor CCR1 in multiple myeloma, free fatty acid receptor FFA2 in type 2 diabetes, and muscarinic receptors, her lab screens in disease-relevant cell lines and looks early for signaling bias - not as a theoretical exercise, but as a practical filter on what a compound might actually do in a patient. That discipline led to a finding her field had not documented before: constitutive beta-arrestin activity at a wild-type FFA2 receptor, suppressible by an inverse agonist that then redirects signaling toward GQ coupling. For Gilchrist, the result was not a surprise so much as a confirmation - if you look in the right system, receptors show you things overexpression models never could. ABOUT THE GUEST Annette Gilchrist is Associate Professor of Pharmaceutical Sciences at Midwestern University, where her research focuses on GPCR signaling in disease-relevant contexts. Her lab studies chemokine receptor CCR1 in multiple myeloma and cancer-to-bone metastasis, free fatty acid receptor FFA2 in type 2 diabetes, and muscarinic M2 and M3 receptors, consistently prioritizing native and disease-proximal cell systems for screening. Before returning to academia, she co-founded two GPCR-focused biotechs with Heidi Hamm - CUE Biotech and Caden Biosciences - developing G-protein C-terminal mini-gene peptide tools that became widely adopted across the field. She also brings early industry experience from Pfizer, where her first sustained encounter with pharmacology as a discipline shaped how she has thought about the relationship between target validation and drug development ever since. SCIENTIFIC THEMES OF THE CONVERSATION The native cell argument - why overexpression models produce systematically misleading screening data and what disease-relevant cell lines reveal instead The practical limits of biased agonism - cell-type context, effector availability, and why the G-protein vs. beta-arrestin framing rarely holds at the clinical level Constitutive beta-arrestin activity and inverse agonism - a first-in-kind finding at wild-type FFA2 and its implications for biased ligand campaign design GPCR pharmacogenomics - natural receptor variation, interpatient drug response differences, and a largely unexplored opportunity in existing drug pipelines Antibody therapeutics for GPCRs - the pipeline case, the approval rate argument, and why orphan receptor targeting may not require knowing the endogenous ligand Receptor dimerization - BRET biosensors, what we still do not know about physiological relevance, and why the tools are finally beginning to close the gap KEY INSIGHTS FROM THE CONVERSATION The cell you screen in determines the biology you can find Running a GPCR screen in a HEK cell overexpression model removes the intracellular proteins a receptor actually encounters in disease tissue - effectors like Go or Gz that are critical in neuronal signaling, for example, and simply absent in standard lines. Gilchrist has argued for disease-relevant cell systems for over 15 years, and her lab's discovery of constitutive beta-arrestin activity at FFA2 is a direct product of that discipline - a result that would have been invisible in a standard overexpression model. Biased agonism is context-dependent, not receptor-intrinsic The field has treated biased agonism largely as a property of a compound and a receptor. Gilchrist's argument is that it is also a property of the cell. The same compound may produce a functionally meaningful shift in one cell type and a negligible one in another, depending on the G-protein isoforms present, the receptor conformation in that membrane environment, and what other proteins are competing for the same intracellular space. How much bias is enough is not a pharmacological question with a single answer. An inverse agonist where none had been reported - constitutive beta-arrestin coupling at FFA2 Gilchrist's lab entered the FFA2 project looking for GQ-biased agonists to drive insulin release. What they found instead was that FFA2 appears to be constitutively coupled to beta-arrestin in the relevant cell system - and that an inverse agonist against that constitutive activity effectively redirects the receptor toward GQ coupling. It was a result that had been documented in a mutant vasopressin receptor but never in a normal wild-type receptor. The aha moment was not the result itself but recognizing what it meant for how you could design the campaign. Pharmacogenomic variation in GPCRs may already be shaping clinical drug response - unacknowledged A paper by Hauser mapped pharmacogenomic variation across the GPCR-ome and showed, among other findings, that many of the GPCRs carrying the highest mutation loads are hormone receptors - FSH, LH, and others implicated in fertility. Patients taking drugs that target GPCRs with natural population-level variants are almost certainly responding differently based on their receptor genetics. Almost no company with an approved GPCR-targeting drug has gone back to look at what common receptor variants do to their compound. Gilchrist believes they should. The mini-gene origin: reading one paper, seeing the missing experiment While a postdoc in Heidi Hamm's lab, Gilchrist read a paper describing how BARK C-terminal peptides had been inserted into a plasmid as tools. The question that followed was immediate: why hadn't anyone done the same with G-protein C-termini? The peptides she developed - 11 amino acids rather than 55, which created their own detection challenges - became widely used across the field for measuring receptor-G-protein interactions and screening for allosteric modulators. The insight was not a long deliberation. It was a single reading of someone else's work and a recognition that an obvious experiment had not yet been done. Antibody therapeutics for GPCRs: the pipeline argument Biologics have a substantially higher success rate than small molecules moving through the drug development pipeline. GPCRs are well-validated targets with known physiological relevance. The combination of those two facts, Gilchrist argues, makes antibody-based GPCR therapeutics an underexplored area - particularly for orphan GPCRs, where compounds are already being developed against receptors whose endogenous ligands remain unknown. The precedent of drugging a receptor without knowing what activates it naturally, and getting therapeutic results, suggests the field does not always need the full biology before it can act on the pharmacology. The first screen: looking for antagonists, finding agonists instead The principle that Gilchrist now teaches - follow the unexpected result, ask why it happened, do not repeat it away - came from her own first encounter with exactly that situation. Running a small-molecule screen in Heidi Hamm's lab, looking for compounds that would block G-protein binding, she found agonists: compounds that made the G-protein bind better, some of which trapped the receptor in a state where it could not signal further. It was not the experiment she had designed. The years of research that followed came directly from not dismissing it. EPISODE TIMELINE Timestamps are AI-generated from the transcript and may not reflect the final edited episode. 00:00 Introduction 02:18 Career trajectory - from medical school intent to Pfizer, PhD in immunology, and an accidental entry into GPCR biology 07:25 Entering GPCR research through Heidi Hamm's lab - and why the committee said G proteins had already won their Nobel Prize 12:39 Co-founding CUE Biotech and Caden Biosciences - allosteric modulator screens and G-protein C-terminal peptide tools 17:17 Current receptors: CCR1, FFA2, and muscarinic M2 and M3 19:28 CCR1 in multiple myeloma - osteoclast/osteoblast imbalance and the cancer-to-bone metastasis problem 23:01 Why native cell lines change what a screen can detect 27:53 The limits of biased agonism - effector context, cell-type dependence, and allosteric complexity 32:08 GPCR pharmacogenomics - variant receptors, the Hauser paper, and what industry has not yet done with existing drugs 39:43 BRET biosensors, receptor dimerization, and what remains unresolved about physiological relevance 42:00 Antibody therapeutics for GPCRs and the case for orphan receptor targeting 48:27 Two aha moments: the G-protein mini-gene origin and finding an inverse agonist where none had been reported SELECTED QUOTES "Being a scientist is like being an artist. You do it because you can't imagine your life doing anything else. I do science because I love science. I love asking a question - I get to find an answer that nobody else knows, potentially." "I had no idea that I would find agonists, biased agonists, as well as antagonists the first time I did my screen. When you have a finding that is completely unexpected, you follow it. You ask the question: why did that happen? Instead of just trying it again." "How much is enough in terms of turning it down? Is a 20% reduction of beta-arrestin signaling enough? I think it is probably cell-dependent. So much of the interaction depends on the conformation of the receptor in that particular cell." "As much as it's been wonderful to get crystal structures and use molecular dynamics, there are still so many questions that we have no idea what the answer is. I guess that's one of the best things about GPCRs - there's always something to look at." About this episode Originally, Annette wanted to be a medical doctor but as luck has it, she didn’t get into medical school when she first applied. Instead, she discovered research and started her Ph.D. the day she should have started medical school. Dr. Gilchrist completed her Ph.D. in Biomedical Sciences / Immunology at the University of Connecticut and went on to become a postdoctoral fellow at UIC (University of Illinois at Chicago). Annette worked in industry, academia and her entrepreneurial side led her to three companies, Cue Biotech , Caden Biosciences , and MyGenomeRx in addition to being a consultant for over a decade. Dr. Gilchrist is also an associate professor at the Department of Pharmaceutical Sciences. Join me and learn more about Annette’s career, our common love for chemokines, and how you can use your training as a scientist in so many different ways. Dr. Annette Gilchrist on the web LinkedIn Midwestern University Google Scholar Pubmed Twitter Research Gate Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Discover how Celtarys Research is transforming GPCR assay development with fluorescent ligands in this episode featuring CSO Dr. Maria Majellaro—and learn what their new partnership with Dr. GPCR means for the global research community. << Back to podcast list Strategic Partner(s) Custom Molecules, Fluorescent Probes: When Chemists Think Like Biologists with Dr. Maria Majellaro from Celtarys A Partnership Rooted in Scientific Innovation In this episode, Dr. Maria Majellaro, CSO of Celtarys Research, shares the story behind the company’s journey from academic curiosity to biotech force. But this conversation also marks something new: a strategic partnership between Dr. GPCR and Celtarys, built on a shared commitment to empowering the GPCR research community. At Celtarys, the focus is on enabling fast, customizable development of fluorescent ligands and chemical probes for GPCR assays. What started as a PhD project has grown into a commercial technology that helps scientists interrogate receptor pharmacology with greater speed and flexibility. “We started with GPCRs, but now we’re expanding to many new targets. Every time, it’s a new world—and we’re still learning.” — Maria Majellaro Through this partnership, Celtarys becomes an integral part of the Dr. GPCR ecosystem, contributing both expertise and tools that align directly with the needs of scientists at the bench and in translational drug discovery. Decision-Making: From Researcher to Scientific Leader Maria’s story is one of trusting her instincts while embracing change. She began as a medicinal chemist in Italy, but a postdoc opportunity in Santiago de Compostela—and a mentor’s timely suggestion—changed her trajectory. When the time came to decide whether to leave the lab and lead Celtarys into biotech, she took the leap. “It was my shift from the lab to leadership. I wasn’t sure at first, but I realized I could do this too.” — Maria Majellaro Her decisions, often made intuitively rather than analytically, have led to key inflection points—including Celtarys’ formal launch in 2021, just as the world was emerging from the pandemic. Now, she leads a team of six scientists and continues to build momentum through collaborations like the one with Dr. GPCR. Translating Science into Business Like many scientists-turned-entrepreneurs, Maria faced the challenge of learning the business side of biotech on the fly. Celtarys had the technology—but not the roadmap for commercialization. That changed with support from Galicia’s robust biotech network, and the company quickly defined its value: building better tools for drug discovery assays. “As scientists, we know how to make molecules. But we had to learn everything else—IP, market positioning, customer discovery.” — Maria Majellaro This year, as part of its partnership with Dr. GPCR, Celtarys will bring those lessons to the broader community, providing insight into assay development, probe design, and the realities of scaling innovation from lab bench to product launch. The Complexity Behind Every “Successful” Probe Maria is candid about the technical challenges behind fluorescent ligand development. “It’s not just attaching a fluorophore,” she says. Each probe must retain activity, remain soluble, and be compatible with a given assay format. There were moments of doubt and repeated optimization. The payoff? Enabling companies and academic labs to avoid the costly dead ends often associated with probe development. “You can have a great ligand—but if you can’t solubilize it, it’s useless.” — Maria Majellaro Celtarys’ unique chemical platform shortens development timelines and allows tailored modifications—critical for labs starting new GPCR-related projects. Their work directly supports the tool-building mission that aligns with the Dr. GPCR ecosystem. Pivoting: From Chemistry Company to Discovery Partner Initially focused on tool production, Celtarys has evolved into something more: a scientific collaborator. Their approach is highly consultative—they don’t just sell ligands, they co-develop solutions. The company works with clients from pharma, CROs, and academia, including MD Anderson and several leading GPCR labs. “We always start with the problem, then generate the right compound using our chemistry. It’s about enabling biology.” — Maria Majellaro Through its partnership with Dr. GPCR, Celtarys will expand its visibility and impact—offering its expertise, tools, and real-world insight to researchers tackling today’s most pressing GPCR-related questions. Key Takeaway This episode is more than a conversation—it’s the official kickoff of a one-year partnership between Dr. GPCR and Celtarys. Together, we’re combining chemistry, biology, and business insight to empower the GPCR research community like never before. Whether you're designing assays, developing probes, or seeking better tools for GPCR drug discovery, Celtarys and Dr. GPCR are now working hand-in-hand to help you do it faster, better, and more reproducibly. About Maria Majellaro Dr. Maria Majellaro obtained her PhD with the distinction of Doctor Europeus from the Department of Pharmacy at the University of Bari (Italy) in 2018. During her doctoral studies, she spent one year as a predoctoral visiting student at the CIQUS Research Center—Campus of International Excellence—in Santiago de Compostela (Spain). In 2018, she returned to CIQUS to work as a Postdoctoral Research Associate in the group of Prof. Eddy Sotelo, where together with Dr. Jhonny Azuaje they laid the groundwork for the future creation of Celtarys Research. Since the founding of Celtarys in 2021, she has served as the company’s Chief Scientific Officer, leading all scientific activities—from the development of Celtarys’ proprietary products to the ideation and execution of custom research projects. She also oversees the company’s scientific collaborations across Europe and beyond, being responsible for securing and managing national and international research grants. To date, she has successfully led seven funded projects. Her scientific expertise is rooted in organic synthesis and medicinal chemistry, with a particular focus on GPCR modulators. She has played a central role in the development and validation of Celtarys’ proprietary synthetic technology and is both a co-author of the related patent and a co-founder of the company. Maria Majellaro on the web LinkedIn ResearchGate Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Bender uses virtual docking to find chemical probes for orphan GPCRs - receptors biology can't study because the tools don't exist yet. << Back to podcast list Strategic Partner(s) Brian Bender: Computational Probes for Orphan GPCR The GPCR superfamily contains hundreds of receptors that cannot be experimentally studied because no usable chemical probe exists for them. Finding an endogenous agonist - when one is even known - is rarely sufficient: a large peptide or lipidated compound may activate a receptor in vivo but is useless as a cell-based tool. This gap is one of the defining bottlenecks in receptor pharmacology, and closing it one receptor at a time will take decades. Brian Bender's work addresses this problem computationally. At UCSF, he develops structural models of GPCRs using sparse experimental data - combining restraints from X-ray crystallography, NMR, and electron paramagnetic resonance spectroscopy - and applies large-scale virtual docking to identify candidate chemical probes across the understudied GPCR landscape. His approach scales across the family rather than stopping at individual targets. Bender trained at the bench before moving fully into computation, and that transition was not planned. A stalled labeling project on the NPY2 receptor during his PhD at Vanderbilt redirected his entire trajectory - and eventually revealed that the patterns connecting receptors across the GPCR family were more interesting than any single structure. ABOUT THE GUEST Bender is a postdoctoral fellow at UCSF working at the intersection of computational structural biology and receptor pharmacology. His research focuses on predicting GPCR structural ensembles from limited experimental data and using virtual docking to identify chemical probes for orphan and understudied receptors. He trained as a structural biologist at Vanderbilt University, working with X-ray crystallography, protein NMR, and electron paramagnetic resonance before transitioning to computation during his PhD work on the NPY2, NPY1, and ghrelin receptors. His fluency in both bench and computational languages shapes how he builds models and how he interprets the experimental data that constrains them. SCIENTIFIC THEMES OF THE CONVERSATION Computational structural modeling of GPCRs from sparse and low-resolution experimental data Virtual docking as a strategy for pan-GPCR chemical probe discovery The orphan receptor problem - why endogenous agonists are not sufficient tool compounds Bench-to-computation transitions and what fluency in both languages enables Family-wide approaches to receptor pharmacology versus single-receptor studies Building scientific community at the early-career stage KEY INSIGHTS FROM THE CONVERSATION The probe gap is a biological bottleneck, not just a chemical one Without a usable chemical probe, a GPCR cannot be studied pharmacologically in a cell-based setting. Even when an endogenous agonist is known, it may be a large peptide or lipidated compound that cannot be practically dosed in vitro. Bender's work targets this gap directly - arguing that de-orphanizing a receptor biochemically and making it experimentally tractable are two separate problems. Virtual docking changes the scale equation Individual bench approaches to identifying tool compounds can take months to years per receptor. Virtual docking screens compress that timeline significantly and can be applied across many receptors in parallel. Bender frames this not as a replacement for bench pharmacology but as the only realistic path to coverage across the full orphan GPCR landscape. The failed experiment that built a career Bender's NPY2 labeling project - designed to generate DEER spectroscopy distance restraints for conformational modeling - never yielded usable data. Rather than a setback, it became a forced pivot into computation at precisely the moment his modeling skills were becoming sufficient to carry a project independently. The stalled experiment was the origin point of the approach he now applies at family scale. Bench experience as a modeling guardrail Knowing what an EC50 means experimentally, or what a Bmax implies about receptor expression, changes how computational restraints are built and applied. Bender credits his time at the bench with preventing the kind of over-interpretation that models built purely from computational intuition can produce - a perspective that shapes how he translates collaborators' data into structural constraints. The eureka of the whole family Months of manually reading sequence alignment tables - before Bender could write the scripts to automate the analysis - produced an unexpected result: structural and sequence patterns connecting receptors across GPCR subfamilies that he had not been told to look for. That period of laborious, close-range data inspection became the conceptual foundation of his pan-GPCR approach, and the moment he understood that one receptor was not enough. Connecting scientists is its own form of science Bender's role co-chairing the Gordon Research Seminar on Molecular Pharmacology is not separate from his scientific work - it is continuous with it. He articulates that the lateral connections formed at early-career conferences, between people who will be colleagues for the next 20 years, are a different kind of scientific output but no less consequential for where the field goes next. EPISODE TIMELINE Timestamps generated with AI assistance and are approximate. They may vary slightly from the final edited version. 00:00 Introduction 01:31 From structural biology to GPCR computation - how the path began 05:47 Modeling GPCR conformational ensembles from sparse data 07:44 Origin moment - a lab notebook at age 8 11:53 The NPY2 labeling project that stalled - and the pivot it forced 17:22 From NPY2 to ghrelin - when one receptor becomes a family question 19:54 Joining UCSF and building the pan-GPCR docking pipeline 21:53 Co-chairing the Gordon Research Seminar on Molecular Pharmacology 47:42 Why orphan receptors need chemical probes, not just endogenous agonists 52:54 Bench fluency as a guard against over-interpreting computational models 58:16 Advice for early-career scientists on connecting with the field 01:02:48 Eureka moment - patterns across the whole receptor family, read by eye SELECTED QUOTES "Are they crazy? Do they know the gold mine that they just gave me?" "It's hard to ever leave the GPCR world once you go into it, just because the longer you stay in it, the more you realize we still don't know in this family." "Taking time to think about what you're doing is way more valuable than just trying to do the next ten million experiments all at once." "I have to go into more receptors. I can't stay with just the one." About Dr. Brian Bender Dr. Bender completed his undergraduate studies at Colgate University in upstate New York with a degree in Biochemistry. Between undergraduate and graduate school Brian worked as a technician in an academic lab before moving to Nashville, TN for graduate work at Vanderbilt University where he joined the Department of Pharmacology. Brain’s work there primarily focused on structure prediction of GPCRs from sparse experimental data. He then moved to the University of California in San Francisco to continue his training as a postdoctoral researcher where he used structural models of GPCRs to virtually screen large compound libraries with the goal of finding new chemical matter to probe understudied and orphan receptors. Brian is involved in organizing the GRC/GRS Molecular Pharmacology meeting, which has been postponed to 2023. Brian is one of the organizers of the upcoming Transatlantic ECI GPCR Symposium . Dr. Brian Bender on the web LinkedIn Twitter ResearchGate Dr.GPCR Member Google Scholar Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. 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Dr. Alex Serafini shares why pain research must start with real-world behavior and models before drilling into GPCR targets — a top-down rethink for drug discovery. << Back to podcast list Strategic Partner(s) GPCRs and the Science Behind Pain and Recovery with Dr. Alex Serafini Strategy: From Personal Pain to Scientific Purpose Dr. Alex Serafini’s entry into science wasn’t typical. Born in California, raised in Silicon Valley, and initially eyeing finance, his trajectory took a sharp turn after struggling with unresolved, chronic pain following repeated surgeries for a pilonidal cyst. "I wasn't able to get stronger pain meds because of the opioid epidemic," he recalls. That gap in care sparked a curiosity that became a career. Driven by personal experience and a desire to innovate in pain management, Alex pursued a master's in pain research at Hopkins and later an MD-PhD at Mount Sinai. His early exposure to TRPV1 channels and peripheral pain mechanisms with Dr. Mike Caterina laid the foundation. But the deeper mission? Finding answers for patients society often overlooks. Pain became more than biology — it became a personal strategy. “I started going through what I was going through… and that got me very interested in research.” — Alex Serafini Decision-Making: Saying Yes to the Unorthodox Path Serafini’s journey defied traditional checklists. He joined Mount Sinai through FlexMed — bypassing the MCAT — and was torn between a career in pharma and academia. At one point, he had a job offer at Roivant (a biotech firm known for repurposing shelved compounds), but a late-stage offer into an MD-PhD program — and parental “encouragement” — rerouted his path. His approach to decision-making is pragmatic: follow impact, not orthodoxy. The decision to stay on as a postdoc in the same lab as his PhD — with Dr. Venetia Zachariou — wasn't the typical next step, but it allowed him to wrap up high-impact work and learn about PI-level grant writing, strategy, and lab management. In his words: “She let me run projects like a junior PI.” “I didn’t need to chase new techniques — I needed to finish the science that mattered.” — Alex Serafini Blind Spots: The Underestimated Role of RGS Proteins in Pain Although not a self-proclaimed GPCR specialist, Serafini found himself repeatedly drawn to them, or more precisely, to RGS (Regulators of G protein Signaling) proteins. The lab’s work with RGS4 led to unexpected results: knockout mice spontaneously recovered from chronic pain after three weeks, an effect rarely observed. He points out that GPCRs—especially orphan and CNS-associated ones—are often downplayed in pain research, with most focus on ionotropic targets like NAV1.8. But Serafini believes that’s a blind spot. “We’re using outdated drugs. There are more elegant GPCR targets waiting to be explored.” The lab’s unconventional in vivo-first strategies, combined with RNA-seq and behavioral analysis, revealed nuanced roles of RGS4, RGS9, and RGSZ — not just as modulators but as potential therapeutic linchpins. “Half the time, in pain, what works in vivo doesn’t translate to clinic. We need new thinking.” — Alex Serafini Failure & Frustration: From Pipettes to Pandemic Disruption The road hasn’t been smooth. From struggling to grip mice in early animal studies to thesis delays during COVID-19, Serafini's journey is marked by grit. But it’s in these friction points that new insights emerged. The pandemic disruption, for instance, led him to BSL-3 labs to study persistent pain after SARS-CoV-2 infection, revealing novel immune-neuron signaling in DRGs. He also opens up about the emotional and logistical toll of MD-PhD training. It’s an eight-year-plus haul with built-in uncertainty. However, with mentors who believed in him, especially those who shared administrative, grant-writing, and leadership skills early on, he found direction and resilience. “She [Vanna] gave me a crash course in what it’s like to be a junior PI. That changed everything.” — Alex Serafini Pivoting: Redefining the Pain Research Playbook Looking ahead, Serafini’s vision is bold: build a lab that develops translational models of pain rooted in patient realities. He’s fascinated by transgenerational epigenetics — how parental pain, diet, or drug exposure can leave molecular fingerprints in offspring. He's equally focused on sex differences in pain processing and the failure of "one-size-fits-all" models in pharmacology. His advice? Learn broadly. Stay close to patients. Collaborate relentlessly. And above all, don’t be afraid to start from the phenotype and work backwards to the mechanism. That top-down approach, though less common, could help pain research finally catch up with the complexity of real-world biology. “Start from the end — from the clinic — and then build backwards.” — Alex Serafini Key Takeaway Innovation in pain research won’t come from doing the same things better — it’ll come from flipping the script. Whether it’s challenging legacy targets, redefining preclinical models, or exploring the epigenetic inheritance of pain, Dr. Serafini urges the field to stay bold, patient-centered, and GPCR-aware. About Alex Serafini Alex was born and raised in the Bay Area and received his BS/MS Neuroscience from Johns Hopkins. His master's degree was in Dr. Michael Caterina's lab studying the role of PNS chloride transporters in neuropathic pain. Upon matriculating to Mount Sinai's MD/PhD program, he joined Dr. Venetia Zachariou's lab to study the effects of chronic pain and addiction/withdrawal on the mesocorticolimbic system, focusing on transcription factor and RGS protein maladaptations, behavioral RGS protein drug "screening", and the role of SARS-CoV-2 on CNS function and sensory hypersensitivity. He aspires to become a physician-scientist, with a focus on translational in vitro and in vivo model development for studying chronic pain and affective comorbidities. Other academic interests of his include studying pharmaceutical finance & healthcare administration and developing technologies that increase healthcare access. His non-academic interests include traveling, scouting out micro-breweries, and collecting beer cans. Alex Serafini on the web LinkedIn Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Dr. Antonella Di Pizio on building computational models for GPCRs with almost no crystal structures and almost no ligands — bitter taste receptors, odorant receptors, and the trace amine-associated receptors that may one day treat depression. << Back to podcast list Strategic Partner(s) Antonella Di Pizio: Computational Pharmacology of Taste and Olfactory Receptors Chemosensory receptors — bitter taste receptors (TAS2Rs), odorant receptors, and trace amine-associated receptors (TAARs) — sit among the most structurally underserved families of class A GPCRs. No crystal structures exist for most of them, sequence identity within the TAS2R family hovers between 15% and 19%, and several members are effectively orphans with only a handful of known ligands. Yet these receptors appear to govern far more than flavor and smell. Bitter taste receptors have been identified in the heart and intestine, olfactory receptors in the brain, and the TAARs sit at the interface between neurotransmission and chemoreception — with clinical interest emerging in schizophrenia, neurodegeneration, depression, and anxiety. In this conversation, Dr. Antonella Di Pizio — who leads the computational pharmacology group at the Leibniz Institute for Food Systems Biology at the Technical University of Munich — describes how she uses homology modeling, docking, molecular dynamics, and iterative mutagenesis to probe these systems. For her, the work isn't abstract: she spent five months staring at empty protein crystals during her PhD, and learned that the distance between giving up and seeing a ligand inside a binding pocket can be measured in weeks. About the Guest Dr. Antonella Di Pizio is an independent research group leader in computational pharmacology at the Leibniz Institute for Food Systems Biology at the Technical University of Munich, where she was the first group leader appointed to the institute's newly-formed in-silico department. Trained as a medicinal chemist at the University of Chieti in Italy, she completed her PhD in computational medicinal chemistry before spending a formative period in Gerhard Klebe's structural biology lab in Marburg. Her postdoctoral training in Masha Niv's lab in Israel marked her first work on GPCRs, specifically the bitter taste receptors (TAS2Rs). Her group now studies taste receptors, odorant receptors, and trace amine-associated receptors using a combination of homology modeling, docking, molecular dynamics, and virtual screening — tightly integrated with experimental mutagenesis and functional assays through collaborations. Scientific Themes of the Conversation Chemosensory receptors as a frontier for GPCR drug discovery Trace amine-associated receptors (TAARs) and their neurological relevance Promiscuity and selectivity within the bitter taste receptor family Iterative integration of computational modeling with experimental mutagenesis Ectopic expression of taste and odorant receptors beyond their namesake tissues Persistence, career building, and what it means to lead a first-generation computational group Key Insights from the Conversation The first in-silico group inside a food biology institute. When Dr. Di Pizio arrived in October 2018, she founded the first computational group in an institute whose original identity had been food chemistry. Her job description — computational pharmacology — was itself an attempt to name a new interface between food chemistry and receptor pharmacology. TAARs look more classical than most chemosensory GPCRs — and that matters for modeling. Unlike bitter taste receptors, which share only 5–10% sequence identity with available structural templates, the TAARs share roughly 30% identity with the β2-adrenergic receptor. That proximity transforms what's computationally tractable, making homology modeling genuinely predictive rather than speculative. TAAR5 is effectively orphan — and may be a new kind of antidepressant target. With only about five known agonists, TAAR5 sits in a pharmacological twilight. Yet knockout mice show anti-anxiety, anti-depressant phenotypes, and expression of the receptor in the brain alters serotonin levels. An antagonist of TAAR5 could, in principle, seed a new class of psychiatric therapy. Bitter is not only about taste. TAS2Rs have been identified in the heart and intestine; olfactory receptors in the brain. What they do there remains largely unknown. But evidence is accumulating that bitter taste receptors participate in innate immunity, recognizing bacterial secretions that happen to register as bitter on the tongue. A bitter receptor is already in phase 2 clinical trials. Isohumulones — the hop-derived bitter compounds that give beer its characteristic flavor — have shown anti-diabetic activity in clinical development. The receptor responsible, TAS2R1, is expressed in the intestine. The drug candidate was never designed as a bitter receptor ligand; the receptor was identified post-hoc. Computational pharmacology is not a downstream silo. Dr. Di Pizio's workflow is deliberately iterative: build the model, predict binding-site residues, send them out for mutagenesis, fold the experimental results back into the model, rebuild. Collaborators are not recipients of finished predictions — they are partners embedded in the modeling loop itself. Five months of empty crystals, then a ligand. During her PhD, Dr. Di Pizio spent five months crystallizing carbonic anhydrase 2 with small molecules and seeing only empty proteins at the synchrotron. Two weeks before her internship ended, after changing every parameter she could think of, she finally saw her ligand inside the binding pocket. She describes it as the happiest moment of her scientific life — and, for a computational chemist, a lasting lesson in what sits behind every coordinate file. Episode Timeline Timestamps were generated using AI for readability. 00:00 Introduction 01:46 Computational pharmacology inside a food systems institute 03:13 From medicinal chemistry to bitter taste receptors 05:44 Trace amine-associated receptors on the edge of neuroscience 12:34 Anosmia and viruses of the olfactory system 19:03 Inside a computational workflow for orphan receptors 29:14 Bitter receptors in the heart and gut 30:43 A bitter receptor in phase 2 clinical trials 43:40 Five months of empty crystals 55:56 Rebuilding a research group during lockdown Selected Quotes "We don't have any crystal structures. So the research is more food-oriented and food-chemistry-oriented — this is why we have knowledge about compounds, but we don't have a lot of knowledge about quantitative structure-activity relations based on the structure of the receptor." "For five months, my protein was always empty at the X-ray. And two weeks before I had to leave, I finally saw my ligand inside the pocket. For me, I think that was my happiest moment in my life." "You share your research goal with your collaborators. They are more partners than collaborators." "Think of being an investor of yourself. Read, study, do the most as you can to learn as much as you can — not only scientifically, but also networking. Be passionate on exactly the field that you work on, because this will be extremely useful later." About this episode In this episode of the Dr. GPCR podcast , we meet with Dr. Antonella Di Pizio, an independent research group leader at the Leibniz Institute for Food Systems Biology at the Technical University of Munich. Antonella trained as a medicinal chemist in Italy, followed by a Ph.D. in computational medicinal chemistry, during which she developed a taste for structural biology. Antonella then moved to Israel, where she first started working on bitter taste GPCRs in Dr. Masha Niv's lab . Today, Antonella has expanded her research to olfactory GPCRs and trace amine receptors. Join us to learn more about chemosensory GPCRs and how computational pharmacology can help better understand their function. Dr. Antonella Di Pizio on the web Leibniz-Institute for Food Systems Biology at the Technical University of Munich Google Scholar PubMed LinkedIn Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

GPCR pharmacologist Dr. Arun Shukla on how two beta-arrestin isoforms regulate over 800 receptors, why "non-canonical" GPCRs are nature's own biased receptors, and building a structural pharmacology lab in India. << Back to podcast list Strategic Partner(s) Arun Shukla: How Two Arrestins Regulate 800 GPCRs The human genome encodes more than 800 GPCRs — and just two beta-arrestin isoforms to regulate their signaling, endocytosis, and degradation. How two structurally similar proteins orchestrate such functional diversity across an entire receptor superfamily remains one of pharmacology's most stubborn unsolved problems. Dr. Arun Shukla's lab at the Indian Institute of Technology, Kanpur attacks this question from multiple angles: structural snapshots by cryo-EM and crystallography, dynamic information from NMR and hydrogen-deuterium exchange, and custom-engineered antibody fragments that both stabilize transient complexes and report on their conformations in live cells. His team also works on so-called non-canonical GPCRs — receptors once dismissed as non-functional because they don't couple to G proteins — and has helped establish that these are, in effect, nature's own beta-arrestin-biased receptors. For Dr. Shukla, the question of how two proteins manage 800 others isn't abstract — it's the one that pulled him back from Lefkowitz's lab at Duke to build a structural pharmacology program from the ground up in India. About the Guest Dr. Arun Shukla leads a structural pharmacology lab in the Department of Biological Sciences and Bioengineering at the Indian Institute of Technology, Kanpur. His research focuses on the structural and functional basis of GPCR–beta-arrestin interactions, combining cryo-electron microscopy, X-ray crystallography, NMR, hydrogen-deuterium exchange, and engineered antibody fragments to resolve how beta-arrestins recognize and regulate a diverse receptor family. He completed his PhD at the Max Planck Institute of Biophysics in Frankfurt and postdoctoral training in Bob Lefkowitz's lab at Duke University before returning to India in 2014. Among his lab's contributions are antibody-based intrabodies that inhibit receptor endocytosis in live cells and biosensors that visualize beta-arrestin conformations across multiple receptor systems. Scientific Themes of the Conversation The structural and functional basis of GPCR–beta-arrestin coupling How two beta-arrestin isoforms regulate an 800-member receptor family Non-canonical GPCRs as physiological beta-arrestin-biased receptors Engineered antibody fragments as tools for structural stabilization and live-cell conformational reporting The limits and promise of biased agonism in drug discovery Methodological triangulation — pairing static structures with dynamic measurements and cellular validation Key Insights from the Conversation Two proteins, eight hundred receptors The central puzzle driving Dr. Shukla's lab is also one of the field's oldest open questions: how do just two beta-arrestin isoforms, structurally nearly identical, mediate the signaling, endocytosis, and ubiquitination of over 800 distinct GPCRs? The answer lies somewhere in the diversity of receptor architectures — long C-termini versus long ICL3s, phosphorylation patterns, and a conformational flexibility arrestins must dynamically adapt to. The "non-functional" GPCRs were never non-functional Receptors like CXCR7, C5L2, and TQIP6 were long dismissed as non-canonical because they don't couple to G proteins. Dr. Shukla's lab and others have shown they signal robustly through beta-arrestins — which makes them, in effect, physiological examples of the beta-arrestin-biased receptors pharmacologists have been trying to design from scratch. Biased agonism is harder than the opioid story suggested The neat bifurcation between G-protein and beta-arrestin signaling that drove early opioid receptor drug design has not held up cleanly in subsequent studies. Cell context, assay choice, and receptor conformational heterogeneity all contribute to outcomes. The concept remains powerful, but it demands better tools and more careful interpretation than the field initially assumed. An antibody built for one job that did another Dr. Shukla's lab designed antibody fragments to stabilize GPCR–beta-arrestin complexes for structural studies. One of them did the opposite: it disrupted the beta-arrestin–clathrin interaction and became a generic inhibitor of receptor endocytosis. The team kept it. That moment of unplanned utility is a recurring theme in his lab. One biosensor, conserved structure and hidden diversity An intrabody raised against the active conformation of beta-arrestin-1 bound to the vasopressin receptor tail was expected to be receptor-specific. It wasn't. It recognized beta-arrestin-1 complexes for the neurotensin and complement C5a receptors — but not every GPCR. That selective cross-reactivity turned the reagent into a visual probe of which receptor-arrestin pairs share a conformational fingerprint and which don't. The moment research stopped being a question During his master's at JNU, Dr. Shukla wasn't sure research would be his career. Then he started his thesis project and found himself skipping theory classes to be in the lab. That's when the question answered itself. For many scientists, the origin moment is this ordinary and this decisive. What a one-line email to Bob Lefkowitz can do Toward the end of his PhD in Frankfurt, Dr. Shukla wrote to Bob Lefkowitz at Duke — no formal interview, no rotation, just a CV and a short note. Lefkowitz invited him. It's a small correction to the assumption that elite postdocs require elaborate application rituals. Episode Timeline 00:00 Introduction 02:15 From DNA quadruplexes to GPCR structural biology 06:32 The master's project that made research a career 08:35 The puzzle — two arrestins, 800 GPCRs 14:29 Antibody fragments, intrabodies, and biosensors 21:09 Non-canonical GPCRs as nature's own biased receptors 23:43 When biased agonism got complicated 38:55 The intrabody they didn't mean to make 43:36 Building a more diverse GPCR community 49:47 Running a lab in India through the pandemic Timestamps were generated using AI for readability. Selected Quotes "There are more than 800 GPCRs, as you know, but there are only two isoforms of beta-arrestins. They're structurally very similar, but they can have quite a significant degree of functional divergence. The key question that continues to fascinate us is how two isoforms of beta-arrestins are able to interact with such a large repertoire of GPCRs and regulate their function." "I was not, to be honest, sure if research was what I wanted to take up as a career. But once I started working in a research lab for my master's thesis, I loved it so much that I would miss my theory classes to work in the lab. That is where I realized research is what I want to do for the rest of my life." "One name that kept popping up was Bob Lefkowitz. I wrote an email to him. No formal interview, nothing of that sort. I just shared my CV, and he invited me." "Initially we thought — I personally thought — that this is not what we want. But then later we realized in the lab that even if it is not what we want, it can be used for other things." About this episode In this episode of the Dr.GPCR podcast , my guest is Dr. Arun Shukla from the Indian Institute of Technology in Kanpur, India. Arun is currently an Associate Professor & Joy Gill Chair Professor, Intermediate Fellow, Wellcome Trust DBT India Alliance Swarnajayanti Fellow & EMBO Young Investigator at the Department of Biological Sciences and Bioengineering. He earned his master's degree in biotechnology from Jawaharlal Nehru University in India and it was during a biochemistry class where he learned about cell signaling that he became curious and wanted to learn more about it. Arun first started working on GPCRs and their structural characterization at the Max Planck Institute of Biophysics where he completed his doctoral studies in the lab of Dr. Hartmut Michel . Fascinated by GPCRs he wrote to Dr. Bob Lefkowitz and asked him if he could join his lab at Duke University. Dr. Shukla spent several years in the Lefkowitz lab and collaborated extensively with Dr. Brian Kolbika of Stanford University. Join us and learn more about Dr. Shukla’s research and how working in the lab instead of going to classes made him realize that research is what he wants to do for the rest of his life. Dr. Arun Shukla on the web Indian Institute of Technology Dr. Arun Shukla Lab Google Scholar PubMed Wikipedia LinkedIn Twitter Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Translating computational approaches to GPCR biologists with Dr. Riccardo Capelli About Dr. Riccardo Capelli Dr. Riccardo Capelli is an assistant professor in Applied Physics at the Department of Biosciences, University of Milan. He earned his PhD in Physics at the same university, focusing on in silico structural vaccinology and advancing free energy calculation techniques. He then held a postdoctoral position at Forschungszentrum Jülich (Germany), where he worked on calculating ligand binding kinetics using classical molecular dynamics. This was followed by a postdoctoral role at the Polytechnic University of Turin (Italy), where he developed coarse-grained models for self-assembling systems. Now in a tenure-track position, his research spans the development of computational methods such as structure-based models and enhanced sampling techniques, as well as their application to biomolecular systems, mainly on GPCRs activation and dynamics. Dr. Ricardo Capelli on the web Google Scholar ResearchGate Bysky App : @ riccardocapelli.bsky.social Twitter X : @ ric_capelli Computational Structural Biology Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>