Alessandro Nicoli shares how he models olfactory GPCRs with AlphaFold, mentors students, and builds science from scratch in a new lab. A fresh look at computational GPCR research. << Back to podcast list Strategic Partner(s) Smells Like GPCR Spirit: Cracking Olfactory Codes with Alessandro Nicoli The Accidental Path to Science Alessandro Nicoli didn’t grow up knowing he’d be a scientist. Like many, his path to GPCR research wasn’t linear—it evolved through academic exploration and mentorship. “I think I don’t have a linear trajectory… the beauty of seeing molecule design and reactions—thinking you can create molecules—was really exciting.” – Alessandro Nicoli He studied pharmaceutical chemistry in Padua, where his fascination with molecular design first took shape. But it wasn’t until meeting an inspiring professor, Prof. Moro, that he truly saw how molecules could go beyond the bench and interact with biology in powerful ways. The Moment Chemistry Met Biology Nicoli’s turning point came when he realized that molecules weren’t static—they could act , bind , and modulate biological targets. “It was not just a molecule—it was a partner that goes to interact with something else… a protein, DNA, RNA. That opened up a new world.” – Alessandro Nicoli That early spark led him to discover the role of medicinal chemistry and, eventually, molecular modeling. For Nicoli, chemistry became more than reactions—it became a bridge to biological insight. Falling for Computational Chemistry The "second academic love" arrived during his master’s thesis, where Nicoli dove into computational chemistry. “I got to know computational chemistry through a project on BCL2 proteins and drug discovery… I was in love with the topic.” – Alessandro Nicoli Working on docking and NMR studies for cancer-related proteins, he discovered the power of simulation in revealing molecular interactions. That experience convinced him to pursue a PhD and deepen his computational skills—eventually leading him to GPCRs. Finding the Right Mentor and Lab A birthday email changed everything. Professor Moro forwarded a PhD opening from Prof. Antonella Di Pizio’s lab in Munich. It felt serendipitous—and it was. “We had a super match… and after a month, I was already in Germany. I was her first PhD student.” – Alessandro Nicoli Starting from scratch in a young lab wasn’t easy, but it created a unique bond between PI and student. Nicoli thrived in this setting—helping shape the lab and its direction, particularly in computational studies of olfactory GPCRs . GPCRs, Receptors of Infinite Variety When asked about his favorite GPCR, Nicoli refused to pick. “Let’s embrace the challenge to study all of them… they’re unique in how they bind ligands, how selective they are.” – Alessandro Nicoli He emphasized that olfactory receptors , while underexplored, present an incredible challenge. With hundreds of subtypes and very few known ligands, the structure–function relationships remain largely mysterious—and incredibly exciting for a computational chemist. AlphaFold: A Turning Point in GPCR Research When Nicoli began his PhD, AlphaFold hadn’t yet revolutionized the field. But once released, it changed everything. “AlphaFold gave us a face to those proteins… now we have 400 models to start with.” – Alessandro Nicoli He explained how AlphaFold’s predictions, surprisingly close to experimental structures, provided a powerful starting point for docking, dynamics, and ligand design—especially for receptors previously “invisible” to structural biology. Modeling the Invisible: Olfactory Receptors Nicoli’s work centers on predicting ligand binding and receptor behavior for olfactory GPCRs. “The main challenge was: how do we get a face for these proteins when we don’t have ligands?” – Alessandro Nicoli He shared a detailed case study of working on a specific odorant receptor (R5VK1), where they leveraged known active/inactive ligands to validate models through iterative refinement , molecular docking , and mutagenesis-guided optimization . The goal? Build predictive models to discover new ligands . Why Molecular Dynamics Matters For Nicoli, molecular dynamics is more than simulation—it’s how we watch biology move . “You simulate over time… see how receptors move in physiological conditions, with water, membranes, ligands.” – Alessandro Nicoli He emphasized that MD allows researchers to observe allosteric changes , mutation effects , and even ligand entry/exit paths , offering dynamic insights that static structures cannot. It’s a critical complement to experimental work. From Researcher to Mentor: Growing Together Outside his research, Nicoli mentors students, manages interns, and even lectures. Balancing this with a PhD isn't easy, but it’s deeply rewarding. “You have people that rely on you… but you grow together, and that’s the most powerful thing.” – Alessandro Nicoli He reflected on learning to delegate—how hard it was initially to hand over tasks—but how vital it is for team science. He now sees mentoring as a way to shape the next generation while evolving himself as a scientist. Advice, Tools, and the Future of GPCR Research Nicoli offered advice to wet-lab scientists curious about computational work: Start with passion. Learn Python. Explore online resources like “Talktorials.” “We’re living in a golden era for computational chemistry… the tools are out there. You just need the motivation to explore.” – Alessandro Nicoli As for what’s next? More structures, better tools, and deeper insights into the elegant, complex world of GPCRs. He sees a future where wet and dry labs converge , and where computational methods are fully integrated into GPCR drug discovery pipelines. Key Takeaway Alessandro Nicoli’s journey is a compelling example of how computational chemistry can unlock new frontiers in GPCR research , especially in complex areas like olfactory receptors. By bridging structural prediction, molecular dynamics, and ligand discovery, his work not only deciphers biological mysteries but also inspires a new generation of scientists to think computationally. About Alessandro Nicoli Alessandro Nicoli is currently a PhD student in the Molecular Modeling group led by Prof. Dr. Antonella Di Pizio at the Leibniz Institute for Food Systems Biology at the Technical University of Munich (Germany). He obtained an MSc degree in Chemistry and Pharmaceutical Technology from the University of Padua (Italy). His training and passion for computational chemistry started in 2019 during his time at the Molecular Modeling Section (MMS) under the supervision of Prof. Stefano Moro, where he worked on integrated Nuclear magnetic resonance (NMR) and computational modeling strategies to target the antiapoptotic BCL-2 protein family, key regulators of cell survival, using small molecules. He then moved to Germany in 2019 to pursue his PhD. His research focuses on a group of 400 transmembrane proteins known as olfactory receptors, which mediate the sense of smell. Beyond the olfactory epithelium, these receptors are expressed in various tissues, where they play important but not yet fully understood roles in various physiological and pathological processes. Despite their relevance, they remain understudied due to the limited knowledge of their ligands and the lack of experimental structures. Alessandro PhD work aims to fill these gaps by leveraging computational structure-based tools and develop specific protocols to accelerate OR ligand discovery and improve our understanding of olfactory function at the molecular level. Alessandro Nicoli on the web Leibniz Institute for Food Systems Biology at the Technical University of Munich Technical University of Munich Google Scholar Pubmed ORCID ResearchGate X Bluesky Github Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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. Randy Hall About Dr. Randy Hall Randy Hall, Ph.D., is a Professor of Pharmacology and Chemical Biology in the Emory University School of Medicine. Randy received his Bachelor's degree in 1990 from the University of New Hampshire and attended graduate school at the University of California at Irvine, studying the regulation of ionotropic glutamate receptors under the direction of Gary Lynch. After obtaining his Ph.D. in 1994, Randy moved to the Vollum Institute in Portland, Oregon, to do a post-doctoral fellowship in the laboratory of Thomas Soderling studying glutamate receptor trafficking and phosphorylation. In 1996, Randy continued his post-doctoral training at Duke University, where he studied the regulation of adrenergic receptors in the laboratory of Nobel Laureate Robert Lefkowitz . Randy then joined the faculty at the Emory University School of Medicine in 1999. Over the past two decades, his lab has published numerous groundbreaking findings shedding light on the signaling and regulation of GPCRs from the adrenergic, purinergic, glutamatergic, GABAergic, and adhesion sub-families. Most recently, his lab has made a number of seminal contributions to understanding the signaling, regulation and in vivo actions of the neuroprotective receptors GPR37 & GPR37L1 as well as the adhesion GPCRs BAI1, BAI2, and GPR56. Randy’s lab has a special interest in studying disease-associated mutations to human GPCRs that perturb receptor signaling and/or trafficking. Randy has received a number of research prizes, including the PhRMA New Investigator Award, the Distinguished Young Scholar in Medical Research Award from the W.M. Keck Foundation, and the John J. Abel Award from ASPET . In 2014, he was named a Fellow of the AAAS. In 2021, he co-authored the critically-acclaimed memoir of his mentor Bob Lefkowitz, entitled “A Funny Thing Happened on the Way to Stockholm: The Adrenaline-Fueled Adventures of an Accidental Scientist”. Join me to learn more about Randy’s work, hear his insights on the GPCR field, and also hear the story of how he came to co-author the memoir of his legendary mentor. Dr. Randy Hall on the web Hall Lab LinkedIn Google Scholar ResearchGate Dr. Lefkowitz Memoir. Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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 Dr. Tom Sakmar and Dr. Ilana Kotliar built a multiplexed platform to map GPCR-RAMP interactions and uncover autoantibody-driven GPCR signaling in disease. << Back to podcast list Strategic Partner(s) Hacking GPCRs: Tools, Tech & Drug Discovery with Tom Sakmar & Ilana Kotliar In this episode, host Dr. Yamina Berchiche reconnects with Dr. Tom Sakmar , Professor at Rockefeller University, and Dr. Ilana Kotliar , his former graduate student, to explore the development of powerful multiplex tools designed to map GPCR-RAMP interactions across the receptor superfamily. What began as a focused exploration into Family B GPCRs evolved into a comprehensive resource for the GPCR research community — bridging wet-lab experimentation, open-access tools, and computational biology. A Long-Term Vision Realized “We've done this work for the past 30 years.” – Tom Sakmar Dr. Sakmar recounts how a fateful phone call from Bruce Merrifield decades ago inspired his lifelong focus on Family B GPCRs. That curiosity laid the foundation for a broader investigation into receptor activity-modifying proteins (RAMPs) . The lab’s early partnership with students like Emily Lorenzen catalyzed a transition from single-receptor studies to multiplexed approaches , opening doors to high-throughput interaction mapping. From Curiosity to Collaboration “We decided to evaluate the multiplexing methods... and found this Luminex assay.” – Tom Sakmar After exploring several screening techniques, the lab adopted the Luminex bead-based assay , which allowed simultaneous detection of multiple GPCR-RAMP interactions. This methodology was enhanced through collaboration with Jochen Schwenk’s lab at SciLifeLab in Karolinska. The result: a scalable platform to analyze hundreds of interactions with minimal sample usage. A Rotation That Changed Everything “I really love this project. I want to take it forward.” – Ilana Kotliar Dr. Kotliar joined the Sakmar lab as a rotation student and immediately saw the project’s potential. She expanded the original Family B focus to encompass the entire GPCR superfamily , building a digital and physical toolkit to systematically investigate GPCR-RAMP biology. Her goal was ambitious: map the complete interactome and validate findings in both overexpression and native contexts. Tools for the Community “We have a library on Addgene... dual-epitope tagged GPCRs.” – Ilana Kotliar The team developed two main assets: A web interface to visualize antibody validations and GPCR-RAMP interactions. A DUET-tagged GPCR library (220 constructs) available through Addgene , enabling labs to explore interactions with ease. These tools are fully open to academic researchers , with wide applicability beyond just RAMPs — including scaffold proteins, disease markers, and heterodimerization partners. Driving Impact through Open Science “500+ requests have come in for these clones.” – Tom Sakmar Dr. Sakmar highlights the vital role of Addgene in distributing the DUET library. The logistical lift was considerable — involving extensive 96-well plate work and documentation — but the team prioritized accessibility over proprietary restrictions. Their ethos: empower fellow scientists, not profit from them. Beyond GPCR-RAMP: New Avenues “What if your favorite scaffold protein interacts with GPCRs?” – Tom Sakmar The constructs aren’t limited to RAMP interaction studies. They can be used to probe GPCR associations with any protein , from cytoskeletal scaffolds like 14-3-3 and P11 to disease-linked interactors . The system is modular and adaptable, opening doors for systems biology and context-specific interaction mapping . A Diagnostic Future “Autoantibodies targeting GPCRs might drive disease.” – Tom Sakmar One especially exciting avenue is autoimmune and infectious diseases . The team envisions using these tools to detect GPCR autoantibodies , which are implicated in conditions like long COVID and Graves’ disease . Unlike blocking antibodies, some autoantibodies activate GPCRs , potentially driving pathophysiology — a paradigm-shifting concept in GPCR immunology. From Many to One: De-Orphanization and Precision Focus “You can use this system to de-orphanize receptors.” – Ilana Kotliar While the toolkit enables broad interactome analysis , it’s also valuable for narrowing in on orphan GPCRs — receptors with unknown ligands or function. This could accelerate discovery of therapeutic targets by combining multiplex data with focused downstream assays. In Ilana’s words, it’s a powerful way to “go from many back to one.” The Shift Toward Technology-Driven Biology “Today’s students want to multiplex, miniaturize, and engineer tools.” – Tom Sakmar Dr. Sakmar reflects on the generational shift in research culture. Instead of focusing on a single receptor, students now gravitate toward platforms , biosensors , and data-rich assays . The multiplex strategy aligns perfectly with this evolution, providing scalable approaches to biological discovery. Global Collaboration and Computational Frontiers “There is no science that ends at a national border.” – Tom Sakmar The success of this project hinged on international collaboration and a multidisciplinary mindset . As the field advances, the computational layer — including AlphaFold and structural prediction tools — will play an increasingly pivotal role. This synergy of wet-lab, in silico, and community-driven resources promises a new era for GPCR systems biology . Key Takeaway This episode is more than a conversation — it’s a masterclass in tool-driven discovery , community science, and the future of GPCR interaction mapping . If you’re working on GPCRs, this is your call to leverage these tools , ask new questions, and help unlock previously hidden layers of receptor biology . About Tom Sakmar Tom Sakmar is a physician-scientist and Rockefeller University professor dedicated to drug discovery and chemical biology research, mainly involving GPCRs. He and his artist/designer wife, Karina Åberg, have three teenage children. Tom Sakmar on the web LinkedIn ResearchGate Pubmed ORCID Google Scholar Rockefeller University Wikipedia About Ilana Kotliar Ilana Kotliar is a 5th year graduate student in the lab of Dr. Thomas Sakmar at The Rockefeller University and just recently defended her PhD thesis. Ilana uses chemical biology-based methods to study the regulation and protein-protein interactions of GPCRs. Ilana’s research is multi-disciplinary and involves a close collaboration with the lab of proteomics expert Dr. Jochen Schwenk, located at The Science for Life Laboratory in Sweden. She is a recipient of the prestigious Women in Entrepreneurship Award, an NIH T32 Training Grant, and two Nicholson Fellowships. Outside of the lab, Ilana is a leader within her community, spearheading several outreach initiatives including a global mentoring initiative that matches graduate student mentors to PhD applicants. Ilana graduated Summa cum laude from Cornell University, where she studied Chemistry and Chemical Biology and was recognized as a Merrill Presidential Scholar. Ilana Kotliar on the web Google Scholar LinkedIn Twitter Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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 Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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) Steve McCloskey About Steve McCloskey Steve McCloskey is an Alumni from the first class of Nanoengineering at the University of California, San Diego. Steve’s work is focused on emerging technologies applied to Science, Technology, Engineering, and Mathematics (STEM). During his time at UC San Diego Steve worked directly with the founding Chair of the Nanoengineering Department, Ken Vecchio helping set the foundation for the Nanoengineering Materials Research Center and developing thermodynamic processing methods for Iron-based Superelastic alloys. After graduating from UCSD he founded Nanome Inc to build Virtual Reality solutions for Scientists and Engineers working at the nanoscale, specifically protein engineering and small molecule drug development. Steve McCloskey on the web Website LinkedIn Twitter ResearchGate Medium Orchid Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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. Eric Trinquet discusses the science and story behind pH Sense, Revvity’s innovative GPCR internalization assay, and his journey in GPCR product R&D. << Back to podcast list Strategic Partner(s) From Rare Earth Probes to Internalization Assays: The pHSense Story with Dr. Eric Trinquet What does it take to design a breakthrough GPCR assay—from idea to industrial impact? In this special episode, Dr. Eric Trinquet shares the inside story behind the development of pH Sense, Revvity’s latest innovation for tracking GPCR internalization. With a career spanning two decades at the intersection of fluorescence chemistry, functional assays, and product development, Eric takes us through the highs, failures, and scientific “aha” moments that shaped tools like the IP-One kit, Tag-lite, and now, pH Sense. If you’ve ever used HTRF or wondered what goes into making a product worthy of your next experiment, this is your backstage pass. You’ll hear what truly makes a reagent successful—and why academic–industry collaborations are essential for advancing GPCR research. Inside This Episode How Eric and his team reimagined rare earth complexes to develop pH-sensitive probes with tunable brightness and lifetime. Why pH Sense enables high-throughput, no-wash tracking of GPCR internalization—even at endogenous expression levels. What shifted the team’s strategy from traditional calcium assays to IP1 accumulation—and why it mattered for Gq-coupled receptors. How collaborations with David Parker and Jean-Philippe Pin accelerated both probe chemistry and biological validation. What it felt like to see the first dose-response curves in native beta cells—and why that moment changed the trajectory of the project. Why the commercialization of a reagent is not the end, but the beginning of a feedback-driven innovation cycle. Why It Might Hit Home If you’ve ever: Wrestled with unreliable endpoint assays or cumbersome radioactive protocols, Pushed for more physiologically relevant systems and hit the “overexpression ceiling,” Balanced scientific rigor with the unpredictability of product development, Or felt the thrill of seeing a tool you built drive real biological insight… …this episode will resonate. About the Guest Dr. Eric Trinquet is Head of R&D for Life Sciences Reagents at Revvity, where he leads innovation in biochemical and cell-based assay platforms. With a foundational career at Cisbio Bioassays—later acquired by Revvity—Eric played a pivotal role in bringing technologies like HTRF, the IP-One kit, and the Tag-lite platform into widespread use. Originally trained as a physicist with a strong interest in photophysics and fluorescence chemistry, Eric transitioned into the GPCR field through hands-on assay development. His passion lies in turning cutting-edge probe chemistry into robust, scalable tools for drug discovery and basic research. What drives him? A mix of scientific curiosity, a tolerance for failure, and a commitment to delivering real-world impact—one product at a time. More about Revvity pHSense Reagents GPCR Reagents Revvity on Dr. GPCR Dr. GPCR X Revvity Collaboration Want more like this? Join the Dr. GPCR Premium Ecosystem for behind-the-scenes access to GPCR innovators, exclusive deep-dives, and practical tools to accelerate your research or career. 👥 Build connections. 🧪 Get insights. 🎧 Stay ahead. 👉 Join now Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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. Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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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<< Back to podcast list Strategic Partner(s) Dr. Stuart Maudsley About Dr. Stuart Maudsley Stuart graduated from the University of Leeds in the U.K. with a First Class Honors degree in Pharmacology. At the end of his studies, he was awarded the Pfizer Prize for undergraduate research. He then completed his Ph.D. at Leeds as well as the University’s Ackroyd, Brotherton, and Brown Scholar. Following his Ph.D., Dr. Maudsley was awarded a Howard Hughes Medical Institute Fellowship to train with Professor Robert Lefkowitz at Duke University. Following this tremendous experience, he was recruited to be the Principal Investigator of the Receptor Biology Section at the Medical Research Council (MRC) -Human Reproductive Sciences Unit within the University of Edinburgh. At the MRC he developed novel prostate cancer therapeutics based upon his research into GPCR pluridimensional signaling. To broaden his biomedical skill-set Stuart next accepted the position of Head of the Receptor Pharmacology Unit at the National Institutes of Health – National Institute on Aging at the Johns Hopkins University Medical Center. At the NIH he was the recipient of the coveted NIH ‘Bench-to-Bedside’ Translational Research Grant Award, one of the few awards available within the intramural NIH program. Upon starting a new family, and returning to Europe, Dr. Maudsley continued his scientific journey with the award of the highly-valued Odysseus Program Type I Program Grant to work as both the Adjunct Director of the VIB Center for Molecular Neurology and also Vice-Chair of the Department of Biomedical Sciences at the University of Antwerp. Stuart’s current research, in the Receptor Biology Lab, focuses on the development of novel GPCR-based therapeutics that interdict diseases based on their gerontological underpinnings. This research stream is now forming the basis of a new technology-based start-up company, HeptOME , to help screen and develop novel longevity/disease-regulating compounds with multidimensional disease efficacy profiles. Dr. Stuart Maudsley on the web Maudsley Lab LinkedIn Google Scholar ResearchGate Maudsley Lab on Facebook Receptor Biology Lab Facebook Group Twitter Semantic Scholar Instagram Neurotree Dimensions Reddit Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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. David Sykes About Dr. David Sykes " David Andrew Sykes, BSc Hons Pharmacology, MSc Molecular Biology and Biochemistry, PhD in Molecular Pharmacology & Drug Discovery. David has over 20+ years of experience working in a drug discovery environment mainly in a specialist assay development role and most recently with Novartis. In 2014 David joined the University of Nottingham and began a part-time PhD in Molecular Pharmacology and Drug Discovery that he was awarded in 2020. During this period David has made a significant contribution to the understanding of agonist/ antagonist GPCR kinetic determinants in an area of growing scientific interest. His current interests include the development of HTS fluorescence-based kinetic binding assays specifically designed to assess the kinetics of unlabelled compounds (and chemical fragments) and the use of purified receptor/ effector proteins as tools for drug discovery. " Dr. David Sykes on the web Veprintsev Lab ResearchGate LinkedIn Dr. GPCR Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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 special university group pricing for Dr. GPCR courses. Save with discounted packages and provide your students or faculty access to premium GPCR learning resources. Empower Your Team with Dr. GPCR Premium Give your team the tools to grow together and stay at the forefront of GPCR science. Save 25% on annual Premium Memberships when you enroll five or more members. Access expert-led courses, 200+ talks, community tools, and curated insights designed to keep your team connected, informed, and inspired. Important Information To qualify for the team discount, your group must include at least five members. If fewer than five members are submitted: • Memberships won’t be activated. • You’ll receive a 50% refund to cover processing costs. 👉 Please double-check your team list before submitting to avoid delays. Questions? We’re here to help: Hello@DrGPCR.org . How It Works? 1 — Prepare Your Team Gather at least 5 scientists who will participate. Each participant must have a Dr. GPCR Ecosystem account . 2 — Submit Your Team Details Provide names, emails, and organization information so we can activate access correctly. 3 — Complete the Payment Secure your team membership and receive confirmation. 4 — Membership Activation Our team activates all seats and confirms access. Activation typically takes 3–10 business days . Need to add members later? Our team can help expand your membership anytime. Apply for Your Team Discount 👇 📢 Limited-time offer – don’t miss out! First name* Last name* Email* Company name* Company Website* Names & Emails of Each Team Member (minimum 5)* Team Size* Annual Premium Team access. Minimum five seats. Priced per person per year. $374.25 Order Now 💡 Have questions? Contact us at Hello@DGPCR.org Book Plan Your Next Move in GPCR Discovery Meet directly with Dr. Yamina Berchiche for a focused strategy conversation to align your goals, uncover opportunities, and map your next steps.

<< Back to podcast list Strategic Partner(s) Dr. Nicholas Holliday About Dr. Nicholas Holliday After an undergraduate degree at the University of Cambridge, Nick carried out his Ph.D. at King’s College London, supported by an AJ Clark Ph.D. studentship from the British Pharmacological Society. It was these studies and subsequent postdoctoral work that led to Nick's interest in peptide messengers regulating appetite, metabolism, and the immune system, and the molecular mechanisms underlying the signaling and regulation of their GPCRs. Nick joined the University of Nottingham in 2006, where he is now Associate Professor, establishing a lab focused on G protein-coupled receptor kinetics, signaling, and trafficking and on using novel imaging techniques, such as fluorescent ligands and complementation methods, to investigate the underlying mechanisms. Since 2019, Nick has combined his university role with the leadership of Excellerate Bioscience as Chief Scientific Officer, a contract research organization specializing in molecular and cellular pharmacology. Excellerate is involved in several pre-clinical drug discovery projects for both GPCR and non-GPCR targets, using its expertise in pharmacology to deliver high-quality target validation, lead optimization, and mechanism of action studies for our clients. Dr. Nicholas Holliday on the web LinkedIn ORCID University of Nottingham Twitter Excellerate Bio Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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. Benjamin Myers About Dr. Benjamin Myers Ben Myers is an assistant professor at the University of Utah School of Medicine in Salt Lake City, UT, and an investigator with the Huntsman Cancer Institute. Ben’s research focuses on Smoothened and other class F GPCRs which play essential roles in embryonic development and in cancer. His group studies the unusual signaling mechanisms employed by these atypical 7-transmembrane receptors, combining biochemical and structural approaches with cell biology and in vivo models. These studies have revealed new and unexpected ways for membrane lipids to regulate GPCR activity and for GPCRs to control intracellular kinases. More recently, Ben’s lab has begun studying GPCR signaling pathways that operate within the primary cilium, a tiny antenna-shaped structure at the cell surface with critical links to development, physiology, and disease. Ben studied developmental and cancer signaling as a postdoctoral fellow with Philip Beachy at Stanford University. Prior to that, Ben received his Ph.D. from UCSF in 2008, where he worked with David Julius on the structure, function, and physiology of ion channels and GPCRs in the nervous system. Dr. Benjamin Myers on the web Website Twitter Pubmed University of Utah Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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. Jean Martin Beaulieu About Dr. Jean Martin Beaulieu Dr. Beaulieu received a Ph.D. in Neurological Sciences from McGill University and completed his post-doctoral training at Duke University. Prior to his recruitment Dr. Beaulieu was an associate professor and Canada Research Chair (Tier2) in the Department of Psychiatry and Neuroscience at Laval University. Dr. Beaulieu’s research is aimed at understanding how cellular and molecular mechanisms regulated by psychoactive drugs intersect with genetic risk factors for mental illnesses such as schizophrenia, depression, and bipolar disorder. Dr. Beaulieu has pioneered work establishing a role for Beta-arrestin signaling in the brain in vivo and has established its importance in D2 dopamine receptors (D2R) functions. These receptors belong to the super-family of G-protein coupled receptors (GPCR), the major molecular target for drug development. In particular, D2R is the main pharmacological target of antipsychotic drugs prescribed for schizophrenia and bipolar disorders. Work by the Beaulieu Lab has demonstrated that mood stabilizer drugs (e.g. lithium) used for bipolar disorder therapy target signaling mechanisms regulated by dopamine receptors, thus providing a framework to understand how different drug classes can engage overlapping cellular mechanisms to exert their action. The Beaulieu group is presently investigating how cell surface express proteins can act as allosteric modulators of D2R signaling and explores the potential usefulness of beta-arrestins for the development of new pharmaceutical agents. Translational validation is important to validate findings obtained from experimental models research and bridge the gap between bench and bedside. Working in collaboration with geneticists, the Beaulieu-Lab has identified interactions between cellular mechanisms engaged by D2R and psychiatric drugs with genetic risk factors implicated in schizophrenia by large whole-genome association studies (GWAS) in humans. These investigations have led to the identification of an RNA binding protein (FXR1P) involved in the regulation of protein synthesis as a potential downstream effector of the action of mood stabilizers and other psychoactive drugs. In addition to basic research, the Beaulieu group is also actively implicated in translational research and industry collaboration to develop new drugs and drug development technology. Dr. Jean Martin Beaulieu on the web University of Toronto Google Scholar LinkedIn ResearchGate Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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) Self-Learning, Collaboration, and Delegation in Science with Dr. Badr Sokrat About Dr. Badr Sokrat " After completing my undergraduate studies with an internship in the laboratory of Dr. Christian Baron studying bacterial secretion systems, I joined the molecular pharmacology laboratory of Dr. Michel Bouvier at the University of Montreal. There, I completed a PhD in biochemistry exploring the non-canonical functions and possible novel mechanisms of regulation of β-arrestin following GPCR activation. Among other projects, I studied the role of β-arrestin in G protein trafficking, the impact of GPCR ubiquitination on signaling and β-arrestin functions, and the characterization of novel β-arrestin interactors. At the end of 2023, I joined the research group of Dr. Nigel Bunnett at the NYU Pain Research Center as a postdoctoral researcher. My current research focuses on investigating GPCR signaling and trafficking in the context of inflammation and chronic pain. I am particularly interested in spatial signaling bias or how GPCRs can redistribute to different subcellular compartments to trigger distinct signaling events. " Dr. Badr Sokrat on the web PubMed ResearchGate LinkedIn Dr. GPCR AI Summary AI-generated content may be inaccurate or misleading. Always check for accuracy. Quick Recap Yamina and Badr discussed their backgrounds in science, their experiences in education, and the challenges of competition and mental health in their home province of Quebec. They also discussed Badr's career trajectory, the importance of self-learning, collaboration, and delegation in scientific research, and the need for a well-organized lab manager in their global scientific team. Lastly, they highlighted the challenges scientists face in academia and industry, the importance of projection and careful communication, and the potential for future collaboration. Next Steps Badr will continue focusing his research on GPCRs involved in pain and inflammation during his postdoc at NYU. Yamina and Badr will create a virtual genealogical tree mapping the connections between researchers in the GPCR field. Yamina will continue to develop and manage the Dr. GPCR University podcast, focusing on collaboration and learning opportunities for the GPCR community. Yamina will balance her scientific work with personal interests and activities to maintain a healthy work-life balance. Summary Podcast Recording and Science Backgrounds Yamina and Badr discussed recording their podcast with Samary Eye, who made a humorous error in transcribing "Edmond" as "agendie". They then shared their backgrounds and interests in science, with Badr recounting his journey from struggling with math in an engineering physics degree to excelling in biology and obtaining a Master’s degree in biochemistry. Badr worked in various science labs, including Dr. Christian Badr’s and Dr. Philip Woozab’s, focusing on bacterial secretion systems, GPCRs, and bioinformatics. Yamina, who also attended the University of Montreal, confirmed her interest in science and mentioned their shared passion for the subject. Education, Competition, and Mental Health Discussion Badr and Yamina shared their experiences about their education, with Yamina sharing her struggles during her first trimester in college and her eventual success due to the support of a theater group and a good teacher. They both discussed the intense competition in their home province, Quebec, and its impact on students' mental health and university admission prospects. They also talked about the negative aspects of this competition, such as students putting others down, and how it can be toxic. Lastly, Badr shared his transition into the field of GPCRs.. Badr recounted Badr's Journey, Multiplexing Assays, and Collaboration Badr shared his learning process and early tasks at Michelle’s lab, which involved creating stable cell lines and identifying potential protein interactions. He described a significant moment when he confirmed a previously uncertain interaction, underscoring the importance of confidence and motivation in scientific discoveries. Yamina emphasized the potential of multiplexing assays in expanding the scope of scientific exploration and finding new protein interactions. They also discussed the concept of serendipity in scientific research, illustrating with examples of Kathleen Curran and her father. Lastly, they concurred on the collaborative nature of the scientific community, where scientists build upon each other's work. Badr's Postdoc Plans and GPCR Research Yamina and Badr discussed Badr’s career trajectory and his decision to pursue a postdoc abroad after his PhD. Badr shared his passion for GPCR signalling and regulation, specifically in the context of pain and inflammation, and how his PhD research on non-canonical GPCR roles laid the foundation for his postdoc work. He also explained his strategy for finding a suitable postdoc lab, which involved reaching out to labs whose recent research aligned with his interests. Lastly, Badr emphasized the importance of choosing a city one would like to live in for several years when deciding on a postdoc position. Badr’s Journey to Overcoming Confidence Fluctuations Badr shared his journey of overcoming fluctuating confidence levels during his PhD journey, emphasizing the importance of viewing failures as valuable learning opportunities. He highlighted that he had to regain his confidence after a period of three failed experiments. Yamina expressed interest in understanding how Badr’s experiences influenced his current role, and Badr stressed the need for individuals to develop challenges outside of their work environment to foster greater confidence. Additionally, they both agreed on the importance of mentorship in building confidence, with Yamina sharing her positive experience of being advised by her supervisor, Nikolaos. Self-Learning, Collaboration, and Delegation in Science Badr and Yamina discussed the importance of self-learning and scientific confidence in managing projects and conducting experiments. They highlighted the significance of collaboration and delegation in scientific research, noting that knowing when to ask for help and when to delegate tasks can lead to more efficient and successful results. Yamina shared her experiences of starting a project independently and then delegating tasks, while Badr shared his plans for his current project, which involved learning certain techniques himself and delegating others to colleagues. They both agreed on the value of these strategies. Yamina’s Podcast Journey and Career Advice Yamina discussed how her podcast on chemokine ligands led to new collaborations and published work. She emphasized preparation and understanding guests’ backgrounds for engaging interviews. Yamina shared her experiences at Rockefeller, where she studied chemical receptors. She aims for Dr. GPCR to serve as a global hub for the GPCR community. Badr expressed interest in broadening his skills beyond the lab, such as project management and effective communication. Yamina advised him to consider career options after his postdoc and adapt to different systems. She highlighted the importance of learning behind-the-scenes skills and staying informed through resources like GPCR news. Improving Scientific Communication and Support Yamina and Badr discussed the need for a well-organized lab manager to facilitate communication within their global scientific team and ensure scientists could focus on their research. They identified the challenges scientists, particularly students and researchers, face, such as imposter syndrome, constant pressure from administrative tasks, and difficulties in maintaining a work-life balance. Yamina and Badr agreed on the importance of individuals struggling with imposter syndrome learning to set aside their fears and doubts to move forward. They also highlighted the benefits of maintaining a supportive network and engaging in non-lab activities for mental processing and relaxation. Academia and Industry Strategies Discussed Yamina and Badr discussed the challenges and strategies of a scientist in academia and industry. Yamina highlighted the need to project a certain presence and balance one’s actions against others in the field. She also mentioned the importance of careful communication, especially when working with a boss who has a different approach. Badr agreed to reach out for a future collaboration, and they discussed the possibility of meeting in Boston. Yamina committed to sending her contact details to Badr. Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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 Webinars 📅 Tuesday, March 3, 2026 at 10:00:00 AM EST 🤝 Webinar in collaboration with: Celtarys Research Fluorescent Probes for GLP-1R and GIPR Imaging: From Cell Assays to In Vivo Systems Fluorescent tools for imaging endogenous incretin receptors across biological systems Interrogating Incretin Receptor Biology Across Biological Complexity GLP-1 and GIP receptors have emerged as central targets in metabolic medicine, yet their precise localization, nanodomain organization, and functional engagement within complex biological systems remain incompletely understood. Fluorescent chemical probes offer one of the most direct approaches for investigating receptor distribution and dynamics in native contexts — without relying on receptor overexpression or genetic modification. This webinar introduces two families of advanced fluorescent probes developed specifically for working with endogenous GLP-1R and GIPR across a range of biological complexity. Attendees will gain a technical understanding of probe design, selectivity, and validated applications — as well as practical guidance on handling, reconstitution, dilution, and storage to support immediate laboratory deployment. LUXendin Family Red and far-red fluorescent GLP-1R antagonists derived from Exendin4(9–39). Enable high-specificity labeling of endogenous GLP-1R in live and fixed cells, pancreatic islets, and whole-organ preparations — without triggering receptor activation. Available across multiple spectral ranges for confocal, super-resolution, and intravital imaging. daLUXendin Family Fluorescent dual agonists for both GLP-1R and GIPR (daLUXendin544+ and daLUXendin660+), structurally related to tirzepatide. Enable simultaneous visualization of endogenous receptor localization and nanodomain organization in pancreatic islet cells and neural sites of action in vivo. Speakers Dr. Johannes Broichhagen Group Leader Leibniz Research Institute for Molecular Pharmacology (FMP), Berlin Dr. Broichhagen trained in chemistry at the University of Erlangen-Nuremberg, completed his doctorate at LMU Munich in 2014, and undertook postdoctoral work at EPFL (Switzerland) and the Max Planck Institute for Medical Research (Heidelberg). Since 2020, he leads an independent research group at the FMP Berlin. His group focuses on the development of chemical tools — including fluorescent ligands and photopharmacological compounds — to investigate GPCR biology with spatial and temporal precision. He is a principal architect of the LUXendin and daLUXendin probe families. Dr. David Hodson Robert Turner Professor of Diabetic Medicine Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford Dr. Hodson is a veterinary surgeon by training who pursued postdoctoral studies at the CNRS in Montpellier before establishing his independent laboratory at Imperial College London as a Diabetes UK RD Lawrence Fellow. He previously served as Professor of Cellular Metabolism and Institute Deputy Director at the University of Birmingham. His research group develops and applies novel technologies to investigate GLP-1 and GIP receptors — two class B GPCRs central to glucose homeostasis, food intake regulation, and inflammation — within complex tissue environments including the pancreas and brain. His work carries direct translational relevance to diabetes and obesity therapeutics. Organizers Celtarys Research Celtarys develops and commercializes fluorescent chemical tools and related screening services that enable fluorescence-based methods across drug discovery. The company's portfolio is built around high-affinity, selective fluorescent ligands for GPCRs, supporting researchers working at the interface of chemical biology and pharmacology. Broad GPCR fluorescent ligand portfolio across multiple receptor families Fluorescence Polarization, HTRF, and High-Content Screening formats Fluorescence microscopy and flow cytometry applications Screening services using proprietary probes in living cells Custom chemical development for probe and ligand creation 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

Eleonora Comeo synthesizes fluorescent ligands to watch adenosine receptor pharmacology happen in living cells - and explains why targeting these receptors keeps failing. << Back to podcast list Strategic Partner(s) Eleonora Comeo: Fluorescent Ligands and the Pharmacology of Adenosine Receptors Adenosine receptors are among the most studied GPCRs in the human body - and among the most difficult to drug. The four subtypes, A1, A2A, A2B, and A3, are expressed across virtually every tissue and implicated in conditions ranging from Parkinson's disease to ischemic heart disease to cancer. Over 40 crystal structures of the A2A receptor alone have been deposited in the Protein Data Bank. Clinical trials have run for decades. And yet approved therapies that selectively target these receptors remain remarkably scarce. One reason is that selectivity in this family is not just a matter of receptor subtype. It is also a matter of G protein coupling, tissue context, and the signaling assay used to measure affinity in the first place - measurements that shift depending on the experimental system. Eleonora Comeo, PhD candidate at the University of Nottingham and the Monash Institute of Pharmaceutical Sciences, is developing fluorescent ligands to address that gap directly - tools designed to visualize adenosine receptor pharmacology at the single-cell level, in environments that better reflect where these receptors actually work. For Comeo, who entered GPCR research without any background in the field and built her PhD around chemistry she could hold in her hand and watch working in a cell, the tools are both scientific instruments and the reason she stayed. ABOUT THE GUEST Eleonora Comeo is a PhD candidate jointly enrolled at the University of Nottingham and the Monash Institute of Pharmaceutical Sciences, working across the groups of Barrie Kellam and Steve Hill. A trained medicinal chemist and pharmacist, her research focuses on the design and synthesis of fluorescent ligands for adenosine A1 and A2A receptors, with the goal of developing chemical tools capable of interrogating receptor pharmacology in physiologically relevant cellular environments. Her work integrates organic synthesis with NanoBRET, SNAP-tag labeling, confocal microscopy, and super-resolution imaging to study receptor localization, internalization, and binding at endogenous and heterologously expressed levels. SCIENTIFIC THEMES OF THE CONVERSATION Fluorescent ligands as pharmacological tools - how synthetic chemistry produces molecules that make receptor behavior visible Adenosine receptor subtype pharmacology - the four subtypes, their G protein coupling profiles, and why ubiquity creates selectivity problems The tumor microenvironment and adenosine-mediated immune suppression - why A2A and A2B are being targeted in oncology Assay dependency and the instability of affinity measurements across experimental systems Endogenous receptor expression in heterologous cell systems - how HEK cell biology confounds fluorescent ligand screening Receptor dimerization - from A2A/dopamine D2 in Parkinson's to A1/A2A in cardio protection, and what remains unresolved KEY INSIGHTS FROM THE CONVERSATION 1. Visibility changes what pharmacology can ask Fluorescent ligands do more than confirm receptor binding - they allow researchers to follow receptors through internalization, track membrane localization, and observe behavior at the single-cell level using super-resolution imaging. Comeo describes the moment she saw her synthesized ligand labeling the cell membrane as one of the most rewarding points in the PhD, precisely because it closed the loop between synthesis and function in a way that binding numbers alone cannot. 2. Ubiquity is adenosine pharmacology's greatest liability The same properties that make adenosine receptors scientifically compelling - their presence in nearly every tissue, their involvement in nearly every major disease class - are what make selective targeting so difficult. Activating or blocking an adenosine receptor for one indication routinely produces off-target effects in another tissue, because the receptor is already doing something important there. The clinical attrition rate in this family reflects that problem more than it reflects a failure of chemistry. 3. Affinity is not a fixed property - it is assay-dependent The apparent affinity of adenosine for its own receptors shifts depending on which downstream signaling endpoint is being measured. A cAMP assay and a binding assay using the same receptor and the same ligand can return different affinity values. Comeo points to this as an underappreciated complication in the field - one that matters not just for scientific interpretation but for how pharmacological classifications like "low affinity" and "high affinity" are assigned across the A2A and A2B subtypes. 4. Tumor cells use adenosine receptors to silence the immune response In the tumor microenvironment, adenosine concentrations are abnormally high. That excess adenosine activates A2A and A2B receptors expressed on immune cells - and that activation suppresses the immune response, allowing tumors to grow unchallenged. Dual A2A/A2B antagonists are now in clinical trials specifically to interrupt this mechanism. Comeo describes this as one of the areas where she most hopes the field can finally validate the receptors as clinical targets, after years of trials that have not delivered. 5. HEK cells are a known confound that still catch researchers out HEK cells endogenously express A2A and A2B receptors at meaningful levels - a fact that complicates fluorescent ligand screening, binding assays, and any experiment where receptor selectivity is the question. Comeo's work uses selective antagonist controls and NanoBRET-tagged receptor constructs to distinguish transfected receptor signal from endogenous background. She also describes recent work in her group using CRISPR-edited cell lines to express receptors at endogenous promoter levels, producing reliable NanoBRET signal even at physiological expression - a methodological advance with implications for how the field studies GPCRs in native-like contexts. 6. Receptor dimerization raises questions the standard pharmacology framework does not address Adenosine receptors form both homodimers and heterodimers with other GPCRs, including A2A with dopamine D2 (a complex investigated extensively in the context of Parkinson's) and A1 with A2A (under investigation for cardioprotection in ischemic heart disease). The biological implications of many of these complexes are still being resolved. During the conversation, an unresolved question surfaced: when a tagged receptor is transfected into HEK cells that endogenously express the same or related subtypes, can the exogenous and endogenous receptors dimerize - and if so, does that alter the pharmacological readout? Neither Comeo nor the host claimed an answer. The question remains open. 7. The hardest transition in a PhD is learning that not knowing the answer is the point Comeo describes the shift from undergraduate training - where not knowing the answer is a liability - to doctoral research, where not knowing the answer is the entire reason the project exists. It is, she notes, a more difficult transition than it sounds, and one that takes time to internalize. The advice she offers to incoming PhD students centers not on technique but on disposition: stay curious about what others are working on, ask for help without embarrassment, and accept that the project is a shared endeavor even when it feels isolating. EPISODE TIMELINE Timestamps are AI-generated from the transcript and should be verified against the final edited audio before publication. 00:00 Introduction 00:44 From Bologna to Nottingham - following her heart into GPCR research 06:49 One year at Monash - starting fresh on the other side of the world 10:02 Adenosine receptor pharmacology and the challenge of targeting four subtypes 16:56 A2A vs A2B - affinity differences, tumor microenvironment, and immune escape 22:08 Why affinity measurements shift depending on the assay 27:09 Synthesizing fluorescent ligands - from crystal structures to glowing molecules 31:03 Following receptors into the cell with super-resolution imaging 36:25 Receptor dimerization - A2A/D2 in Parkinson's, A1/A2A in cardioprotection, and one open question 41:26 Finishing the PhD - what comes next and what she'll miss 42:42 Advice for PhD students - resilience, collaboration, and not fearing the unknown 54:44 The dopamine rush that keeps scientists coming back SELECTED QUOTES "I completely fell in love with that research. And I felt three months wasn't enough for me. So I asked whether they had a PhD opportunity - and here I am." "Just because you can see them. They're really useful because you can see them - you can use them to visualize the process you're interested in. That's what makes it so rewarding." "It's important to understand, in your cellular context, what the expression of the other receptor is - the one you're interested in - because otherwise you can get confounding outputs." "In chemistry, it's like when you finally see the NMR of your structure without anything but your compound - it's just perfect. You can feel the shivering behind your spine. You would just like to run around screaming." About this episode Eleonora Comeo is a doctoral candidate in Medicinal Chemistry and Drug Discovery in the joint program of the University of Nottingham in the UK and Monash University in Australia. We sat down to chat about GPCRs, synthesizing labeled ligands, and her unique position that allows her to work with GPCR scientists on 2 continents. We also touched on how COVID-19 affected her Ph.D. work. Eleonora Comeo on the web LinkedIn ResearchGate Pubmed Google Scholar Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ 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 Your GPCR Order Has Arrived! ❇ Feb 10 - 16, 2025 🚀 GPCR Pals, Get Ready to Elevate Your Expertise! Welcome back to your exclusive GPCR Weekly Newsletter! We’re thrilled to unveil our ever-expanding course roster—designed to help you stay at the cutting edge of GPCR research. New topics, expert-led sessions, and hands-on learning opportunities await! 🎓 Kicking Off Today: Dr. Terry Kenakin ’s hands-on workshop, The Practical Assessment of Signaling Bias . Didn’t sign up? Don’t worry— registrations are NOW OPEN for the 2025 Dr.GPCR University Courses! This is your chance to learn directly from our world-renowned experts. Come back regularly as we are adding courses each month. Email us if you'd like to teach or if you'd like to learn more about any particular topic. 🗓️ Upcoming 4-Week Course: Development of GPCR Ligands as Therapeutic Drugs starting March 20 – April 10, 2025 (Thursdays, 10:00 AM–12:00 PM EST). Watch Dr. Kenakin as he introduces the key concepts of this brand-new course. During these four sessions, you'll dive into: Advanced pharmacokinetic modeling The Druglike Quality of Chemical Entities Drug Absorption 💡 Looking for workshops? We’ve got you covered! ✅ Practical Quantification of Allosteric Modulation – May 1, 2025 ✅ Applying the Black/Leff Operational Model to Predict Agonism – October 2, 2025 Premium Members save 25% on enrollment. Reserve Your Spot Now! 🔗 Register Today . 🔥 Act Fast – Only 25 Spots Available! ⚡ Don’t miss out! Premium Members save 25% on enrollment! Secure your spot today! Highlights of the Week How Ligands Achieve Biased Signaling toward Arrestins Stéphanie Gaillard , Neha Verma , Leisha A Emens , et. al. A combined in silico approach to design peptide ligands with increased receptor-subtype selectivity Adam Zech , Victoria Most , René Staritzbichler , et. al. A2B adenosine receptor-triggered intracellular calcium mobilization: Cell type-dependent involvement of Gi, Gq, Gs proteins and protein kinase C Qin Wang , Wenwen Hao , Jing Li , et. al. Classified GPCR News Let’s dive into the Classified GPCR News from February 10th to 16th, 2025 Industry News Pain targets in ion channel pathways: an Innovation Distillery spotlight ‘It’s not for the faint of heart.’ How 3 CEOs took their biotechs public Aikium's AI-Driven mRNA Engine Looks to Address Undruggable Disordered Proteins Tectonic Therapeutic Secures Massive $185M PIPE Financing for Clinical Programs Septerna Announces Discontinuation of SEP-786 Phase 1 Clinical Trial and Plans to Advance Next-Generation Oral Small Molecule PTH1R Agonist Call for GPCR Papers NEW Special Issue on Adhesion GPCRs GPCR Events, Meetings, and Webinars March 19, 2025 | Advancing obesity drug discovery: Cell-based assays for GLP-1 and the G-Suite March 17 - 21, 2025 | 2nd GPCR signaling and drug discovery Symposium & Workshop NEW April 2 - 3, 2025 | New therapeutic modalities: Transforming receptor pharmacology April 3 - 6, 2025 | ASPET 2025 April 24 - 27, 2025 | American Physiology Summit 2025 April 25 - 30, 2025 | AACR Annual Meeting 2025 May 12 - 15, 2025 | PEGS 2025 May 15 - 17, 2025 | 23rd GPCR Retreat 2025 May 20 - 22, 2025 | SLAS Europe 2025 NEW May 20 - 22, 2025 |4th GPCRs-Targeted Drug Discovery Summit June 22 - 26, 2025 | G Protein-coupled Receptor Kinases and Arrestins NEW December 16 - 18, 2025 |Pharmacology 2025 July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology GPCR Jobs Structural Biologist Associate Director/Director, Platform & Hit-ID Chemistry Lead Junior associate position and a PhD/post-doc level position Postdoctoral Position And PhD Position GPCR Molecular Pharmacologist Scientist - Biology Scientist I Cell Biology - Tectonic Therapeutic Senior Principal Scientist, Medicinal Chemistry PhD fellowship in GPCR mechanosensing GPCR Activation and Signaling Lineage-Specific Class-A GPCR Dynamics Reflect Diverse Chemosensory Adaptations in Lophotrochozoa β-arrestin 1 and integrin-linked kinase interact in epidermal keratinocytes and regulate cell motility The regenerative wound healing effects and molecular mechanism of Isaria cicadae Miquel rice fermentation extract A2B adenosine receptor-triggered intracellular calcium mobilization: Cell type-dependent involvement of Gi, Gq, Gs proteins and protein kinase C GPCRs in Cardiology, Endocrinology, and Taste N-homocysteinylation of β-arrestins biases GPCR signaling and promotes platelet activation GPR180 Reduces Adiposity by Inhibiting Lipogenesis and Fatty Acid Uptake in Adipocytes Derivation of hiPSC line (ICADRB2i007-A-3) from an individual with osteoporosis linked to ADRB2: c.46G > A GPCRs in Neuroscience Effects of chemogenetic virus injection and clozapine administration in spinal cord injury GPR37L1 identifies spinal cord astrocytes and protects neuropathic pain after nerve injury Hypothalamic opsin 3 suppresses MC4R signaling and potentiates Kir7.1 to promote food consumption Reviews, GPCRs, and more How Ligands Achieve Biased Signaling toward Arrestins Structural and Molecular Insights into GPCR Function A combined in silico approach to design peptide ligands with increased receptor-subtype selectivity Ligand-Independent Spontaneous Activation of Purinergic P2Y6 Receptor Under Cell Culture Soft Substrate 🔎 GPCR KEYWORDS Class-A G protein-coupled receptors , Lophotrochozoa , echinoderms , Arrestins , ILK , directional migration , epidermis , keratinocytes , scaffold proteins , β-arrestin , Hippo pathway , IMFRE gels , Regenerative healing , Skin repair , Wound healing , A2B adenosine receptor , Calcium , G protein , GPCR , Gi , Gq , Gs , N-homocysteinylation , Adiposity , Fatty Acid Uptake , Lipogenesis , Induced pluripotent stem cells , Osteoporosis , Reprogramming , AAV5-hSyn-hM3Dq-eYFP , Clozapine , DREADDs , Gq signaling pathway , Neuroregeneration , EPSC , GLT-1 , GPR37L1 , SPM , astrocytes , maresin 1 , microglia , nerve injury , neuropathic pain , spinal cord dorsal horn , OPN3 , cAMP signalin g , MC4R , docking , opioid , peptide ligand design , protein design , Ca2+ oscillation , GPCRs , basal activity , purinergic receptor , substrate stiffness < Previous Next >

< Back Fresh, Fresh, GPCR News ❇ Feb 17 - 23, 2025 Hi friends! Welcome to our weekly update! This week's GPCR roll-up includes the latest insights, research discoveries, and advancements. We'll also preview upcoming courses designed for both experienced researchers and newcomers. 🚀 Develop New GPCR Skills Join Dr. Terry Kenakin’s unique course, Development of GPCR Ligands as Therapeutic Drugs , and gain essential insights into: 🔹 Drug Development Basics – PK-PD insights, absorption, and drug properties 🔹 Clearance & Metabolism – Distribution, renal/hepatic pathways, and elimination 🔹 Safety First – Identifying toxicity risks and drug-drug interactions ⏳ Availability is limited. Register now and shape the future of drug discovery! Premium Members enjoy a 25% discount Secure Your Spot Today! Tune in to Ep.160 of the Dr. GPCR Podcast 🎧 Join Remi Janicot as he shares his educational journey, passion for basketball and science, and career decisions. He discusses biased signaling in GPCR research, developing biosensors for G protein activity, networking, mentorship, PhD resilience, COVID-19 challenges, and his aspiration to transition into biotechnology investment opportunities. Highlights of the week Structural insights into prolactin-releasing peptide receptor signaling and G-protein coupling selectivity Zhangsong Wu , Chen Qiu , Geng Chen , et al. Single-Molecule Insights into GPCR Conformational Landscapes Rajan Lamichhane Discovery of CCR8 Antagonist IDOR-1136-5177 for the Treatment of Cancer Stefan Diethelm , Luboš Remeň , Olivier Corminboeuf , et al. Classified GPCR News Let’s dive into the Classified GPCR News from February 17th to 23rd, 2025 Industry News Septerna Announces Discontinuation of SEP-786 Phase 1 Clinical Trial and Plans to Advance Next-Generation Oral Small Molecule PTH1R Agonist Revolutionizing Protein-Ligand Simulations: OpenMMDL's Open-Source Approach The Rapid Push into Radiopharmaceuticals in Oncology and What’s Next Call for GPCR Papers Special Issue on Adhesion GPCRs GPCR Events, Meetings, and Webinars March 19, 2025 | Advancing obesity drug discovery: Cell-based assays for GLP-1 and the G-Suite - Online March 17 - 21, 2025 | 2nd GPCR signaling and drug discovery Symposium & Workshop - Brazil NEW April 1 - 3, 2025 | 2nd Peptide-Based Therapeutics Summit - USA April 2 - 3, 2025 | New therapeutic modalities: Transforming receptor pharmacology - UK April 3 - 6, 2025 | ASPET 2025 - USA NEW April 14 - 17, 2025 | 20th Drug Discovery Chemistry 2025 - USA April 24 - 27, 2025 | American Physiology Summit 2025 - USA April 25 - 30, 2025 | AACR Annual Meeting 2025 - USA NEW May 1 - 2, 2025 | 5th Ace Drug Discovery Summit 2025 - USA NEW May 12 - 15, 2025 | ACSMEDI-EFMC Medicinal Chemistry Frontiers 2025 - USA May 12 - 15, 2025 | PEGS 2025 - USA May 15 - 17, 2025 | 23rd GPCR Retreat 2025 - USA May 20 - 22, 2025 | SLAS Europe 2025 - Germany May 20 - 22, 2025 |4th GPCRs-Targeted Drug Discovery Summit - USA June 22 - 26, 2025 | G Protein-coupled Receptor Kinases and Arrestins - USA December 16 - 18, 2025 |Pharmacology 2025 - UK July 12 - 17, 2026 | 20th World Congress of Basic and Clinical Pharmacology - Australia GPCR Jobs NEW Open Postdoctoral position - Stanford University Structural Biologist - Confo Therapeutics Associate Director/Director, Platform & Hit-ID Chemistry Lead - Septerna Junior associate position and a PhD/post-doc level position - Eli Lilly and Company Postdoctoral Posit ion And PhD Position - Autonomous University of Barcelona GPCR Molecular Pharmacologist - Schrödinger Scientist - Biology - Superluminal Medicines Scientist I Cell Biology - Tectonic Therapeutic Adhesion GPCRs A force-sensitive adhesion GPCR is required for equilibrioception GPCR Activation and Signaling Extensive location bias of the GPCR-dependent translatome via site-selective activation of mTOR Light intensity-dependent arrestin switching for inactivation of a light-sensitive GPCR, bistable opsin Diapause hormone receptor affects larval growth and embryonic development in the multivoltine strain of Bombyx more Profiling Allosteric Modulators of CB1R with an Allosteric Fluoroprobe GPCRs in Cardiology, Endocrinology, and Taste Immunolocalization and quantification of the phoenixin and GPR173 in the gastrointestinal tract of Holstein-Friesian bulls Derivation of hiPSC line (ICADRB2i007-A-3) from an individual with osteoporosis linked to ADRB2: c.46G > A GPCRs in Neuroscience Cortical astrocyte activation triggers meningeal nociception and migraine-like pain GPCRs in Oncology and Immunology Spatial analysis of a complete DIPG-infiltrated brainstem reveals novel ligand-receptor mediators of tumour-to-TME crosstalk Discovery of CCR8 Antagonist IDOR-1136-5177 for the Treatment of Cancer The extracellular matrix protein type I collagen and fibronectin are regulated by β-arrestin-1/endothelin axis in human ovarian fibroblasts Methods & Updates in GPCR Research Histamine-modulated wettability switching in G-protein-coupled receptor inspired nanochannel for potential drug screening and biosensing Reviews, GPCRs, and more Single-Molecule Insights into GPCR Conformational Landscapes Covalent functionalization of G protein-coupled receptors by small molecular probes A deadly taste: linking bitter taste receptors and apoptosis Molecular roles in membrane receptor signaling pathways and cascade reactions in chondrocytes: a review Is GCR1 the GPR157 of plants? Structural and Molecular Insights into GPCR Function Structural insights into prolactin-releasing peptide receptor signaling and G-protein coupling selectivity Decoding the structural basis of ligand recognition and biased signaling in the motilin receptor 🔎 GPCR KEYWORDS GPCR , structural biology , biased signaling , metabolism , Chondrocytes , Signaling pathway , Integrin , Taste family 2 receptors , Calcium , Cell death , Mitochondria , macrolide antibiotics , motilin receptor , azithromycin , Extraoral taste receptors . < Previous Next >

Discover top GPCR Courses for your educational journey. Explore a curated list of GPCR Courses to enhance your knowledge and career. Stay at the Forefront of GPCR Drug Discovery Gain insider methods from the pioneers shaping biased signaling, assay design, and pharmacology—skills you won't find in any textbook or paper. ⧖ 20+ Hours of Expert Training ↓ Downloadable Resources ◕ New Courses added Quarterly Get Access to GPCR Courses Learn in 3 Simple Steps Free trailers coming soon Preview every masterclass before joining Unlock full access Get Premium for complete library access Learn anytime, anywhere Access on-demand from any device Join Premium Today Unlock Insider Access to GPCR Science! Free updates, exclusive previews, and highlights from our Masterclasses and Vault. First name Last name Email* Join Our Mailing List Count me in! * Explore the Masterclasses Trailers are free. Full classes require Premium. 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The Practical Assessment of Signaling Bias Dr. Terry Kenakin < Back Workshop Summary Join Dr. Terry Kenakin , a leading expert in pharmacology, as he unpacks the fascinating world of signaling bias in drug development! 🚀 This workshop will explore how different ligands (compounds) can stabilize unique receptor conformations, leading to distinct signaling outcomes—even when binding to the same receptor. Dr. Kenakin will explain that bias is not an exception but a fundamental principle of pharmacology, occurring whether or not researchers actively seek it. Through an engaging discussion, you'll explore: 🔹 What signaling bias is and why it matters 🔹 How receptor dynamics shape drug responses 🔹 Cutting-edge methods for quantifying bias 📊 🔹 Strategies to harness bias for better drug design —maximizing efficacy while minimizing side effects The session wraps up with a lively Q&A , allowing attendees to explore this game-changing topic in greater depth. Don't miss this opportunity to refine your understanding of bias as a tool, not an obstacle, in pharmacology! Key Highlights 🔍 Bias is Everywhere : Signaling bias naturally occurs in pharmacology—whether we look for it or not! 🧬 Receptor Flexibility : Ligands stabilize different receptor states, creating unique signaling pathways. 📏 Measuring Bias : New techniques allow us to quantify bias and compare drug efficacy more precisely. 💊 Therapeutic Potential : Understanding bias enables researchers to design drugs that target specific effects while avoiding unwanted side effects. 🗣️ Interactive Q&A : The discussion wraps up with an insightful Q&A, tackling real-world drug development challenges. Deep Dives & Insights 📌 Bias is Not an Anomaly—It’s a Feature! 🔹 Instead of avoiding bias, researchers can embrace it to refine drug responses. Dr. Kenakin challenges the traditional approach and encourages leveraging bias for better therapeutic outcomes. 📌 Receptors are Dynamic Players 🔹 Different ligands trigger unique receptor states, meaning the same receptor can signal in entirely different ways depending on what binds to it. Understanding these shifts can revolutionize drug development! 📌 Measuring Bias: A Quantitative Approach 🔹 The operational model provides a structured way to measure bias, combining affinity and efficacy. This allows for a side-by-side comparison of how different compounds influence receptor signaling. 📌 Bridging the Gap: Lab to Clinic 🔹 While measuring bias in a lab is relatively straightforward, translating these findings to clinical applications remains a challenge . The talk explores how to navigate this crucial gap. 📌 The Future of Drug Development 🚀 🔹 By integrating bias into drug design , researchers can craft more selective, effective, and safer therapies. This approach is shaping the next generation of precision medicine! Dr. Terry Kenakin’s workshop offers a fresh perspective on drug discovery . It shows that bias isn’t something to avoid—it’s something to utilize ! Whether you're a researcher, student, or industry professional, this session is packed with insights that will make you rethink your approach to pharmacology . Ready to explore the future of biased drug design? Let’s dive in! 🔬✨ AI Summary - May contain inaccuracies Materials: BIAS_WORKSHOP_PRINT .pdf Download PDF • 9.11MB BIAS_EXERCISE .pdf Download PDF • 721KB What would you like to learn today?

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