<< Back to podcast list Strategic Partner(s) Dr. Bianca Plouffe About Dr. Bianca Plouffe Dr. Bianca Plouffe obtained her B.Sc. in Biochemistry in 2003 from Université de Sherbrooke (Qc, Canada). She then completed an M.Sc. in Physiology from the same university in 2005 by investigating the molecular mechanisms involved in the angiotensin type 2 receptor (AT2R)-mediated neurite outgrowth while characterizing new selective AT2R agonists. In 2006, Bianca obtained a Doctoral Scholarship from the Fonds de Recherche du Québec en Santé. She moved to the University of Ottawa to complete a Ph.D. in Neuroscience. She identified the molecular mechanisms involved in the opposite regulation of dopamine D1 and D5 receptors by protein kinase C. After obtaining a Postdoctoral Fellowship from the Canadian Institutes of Health Research in 2012, Bianca joined the research group of Prof Michel Bouvier at Université de Montréal. As part of Bouvier’s team, Bianca used Bioluminescence Resonance Energy Transfer (BRET)-based technology to tackle important questions related to GPCRs. She identified the structural determinant controlling biased signaling of melatonin type 2 receptors in the context of protection against type 2 diabetes. Bianca also collaborated with Prof. Robert Lefkowitz , which led to the finding that both β-arrestin and G protein can simultaneously bind to some GPCRs when signaling in endosomes by forming a megaplex. In 2018, Bianca was appointed Vice-Chancellor’s Fellow at Queen’s University Belfast to develop her research program. Funded by a Wellcome Trust Seed Award, she investigated biased and compartmentalized G protein signaling by the vasopressin type 2 receptor. In 2021, Bianca secured a permanent position as a lecturer. Her subsequent work has focused on understanding the role of compartmentalized Gq signaling by the cytomegalovirus-encoded chemokine US28 receptor in the context of glioblastoma. Dr. Bianca Plouffe on the web Queen's University Belfast website LinkedIn ResearchGate ORCID 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 >>

Explore the world of GPCRs with Dr. GPCR Podcast! Join industry leaders as they share insights, stories, and groundbreaking discoveries, enriching our understanding of GPCRs. Delve into the science behind these vital components shaping our collective knowledge. Welcome to the Dr. GPCR Podcast - The Voice of the Community Conversations with the world’s leading GPCR scientists. Exploring discoveries, careers, and ideas shaping human health. In each episode, we sit down with leading experts to explore their career journeys, groundbreaking discoveries, and the impact of their research on our shared understanding of GPCR biology. Launched at the height of the pandemic, the Dr. GPCR Podcast was created with three goals: Share discoveries – Highlight the latest advances in the GPCR field. Amplify voices – Provide scientists a platform to showcase their work. Inspire the future – Motivate the next generation to pursue GPCR research. At its core, Dr. GPCR’s mission is simple yet ambitious: to bring the GPCR community together - across borders and disciplines - to connect, exchange, and collaborate in order to improve human health through a deeper understanding of GPCR biology. Latest Podcast Episodes More podcast episodes Dr. GPCR Podcast Audience Survey We are currently planning our next season and need your help. This short survey will help us understand your needs to bring you exciting and informative content. We also know that you are busy, which is why we designed this short survey that should take you 5 minutes. Fill out this form Be our Guest In each episode, we chat with an expert about their career trajectory, discoveries, and how their research contributed to the shared pool of knowledge about GPCR biology. We’d love to have you on our podcast. To be a guest, fill out the form below, and we’ll be in touch in 48 hours. Fill out this form What others are saying about this podcast "You made it a very comfortable and engaging experience, and it felt like we were chatting over coffee — Yamina thoughtfully guided our chat throughout." Anita Nivedha I think it's really well done. I'm genuinely interested to see how it evolves and grows over time, as I feel it has the potential to develop into something even more impactful. Anonymous This came at just the most perfect time. I hadn't heard a scientific talk outside my lab since February and was starved to hear someone else talk passionately about GPCRs. I've listened to the episodes multiple times and it's just like being at a conference getting new ideas. I just couldn't be happier y'all created this podcast. Anonymous Great initiative, thanks. Carrier paths, choosing research topics, switching fields, late start, failures and successes. Anonymous I enjoy the breadth of questioning that goes beyond just the science, and reveals a bit about the scientists as individuals/mentors/people. Anonymous Really enjoyable science podcast! Dr. Yamina Berchiche interviews leading GPCR scientists on this vibrant, entertaining podcast. I really appreciate the way the podcast educates and mentors, particularly towards junior scientists but also to the community as a wholen Yamina is a great interviewer, getting insight and personal history from her guests. Am very grateful for Dr GPCR livening up the week in these difficult times! Sam @Pharmamechanic Listen and subscribe where you get your podcasts

<< Back to podcast list Strategic Partner(s) Dr. Robert F. Bruns About Dr. Robert F. Bruns Fred Bruns discovered the first positive allosteric modulator (PAM) of a GPCR in the late 1980s while working at Warner-Lambert/Parke-Davis. The work was published in 1990. After 7 years at WL/PD and 26 years at Eli Lilly & Co., he retired at the end of 2014 and since then has been writing papers on his final major project at Lilly, a dopamine D1 PAM series that has advanced through Phase 2 clinical trials. Fred obtained an A.B. in Psychology from Washington University in St. Louis, followed by a Ph.D. in Neurosciences at the University of California, San Diego. His doctoral dissertation was the first large-scale study of structure-activity relationships for adenosine receptors. During a joint postdoc with John W Daly at NIH and Solomon Snyder at Johns Hopkins, he developed the first adenosine receptor binding assay. He then joined WL/PD, where his lab demonstrated the existence of two subtypes of the adenosine A2 receptor, A2a and A2b. In 1988, he joined Lilly as a receptor biologist in charge of a high-throughput screening lab. He taught himself chemoinformatics as a way to optimize compound selection for screening, and in 1997 switched to computational chemistry full-time. He supported the D1 PAM project in various roles from its inception in 2002 until selection of a clinical candidate in 2013. Dr. Bruns has over 80 publications and 11,000 citations, with an h-index of 47. Dr. Robert F. Bruns on the web 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 >>

<< Back to podcast list Strategic Partner(s) Developing new tools to uncover GPCR signaling patterns with Remi Janicot About Remi Janicot I was born in Paris (France) and grew up in Europe until I was 18. After graduating high school, I moved to America to pursue my passion for basketball while continuing high level studies. I played collegiate basketball and earned my bachelor’s at Ursinus College, a small school around Philadelphia where I graduated from in 2018. After that, I worked at Johns Hopkins in Baltimore as a research assistant investigating mechanisms and treatments for pediatric epilepsy. With my background in neuroscience, the lab of Dr. Mikel Garcia-Marcos seemed like a good fit as GPCRs are integral to the functioning of the nervous system (and much more). My particular projects revolve around developing new tools to study GPCR activity in ways that were not previously possible. This research has led to a first-author Cell article on the development of a new biosensor platform called ONE-GO biosensors. Overall, the lab works on diverse models and diseases, and has developed a wide array of tools to dissect GPCR/G protein signaling which I would be happy to discuss. Remi Janicot on the web Chobanian & Avedisian School of Medicine 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. Gregory Tall About Dr. Gregory Tall " Dr. Gregory Tall earned his Ph.D. in Biomedical Sciences from U.T. Southwestern Medical Center with Bruce Horazdovsky, Ph.D. They worked on the interactome of yeast and mammalian Rab5 homologs including identification of Rab5 GEFs. In 2000, Dr. Tall moved upstairs to conduct his postdoctoral work on heterotrimeric G proteins and the novel interactor, Ric-8 with Alfred Gilman, M.D. Ph.D. In 2007, Dr. Tall joined the faculty in the Department of Pharmacology and Physiology at the University of Rochester Medical Center, there establishing his lab and major research directions. Dr. Tall moved to the University of Michigan in 2016 as an Associate Professor of Pharmacology and is a current active member of the department. The current goals of the Tall lab are to understand the basic mechanism by which Ric-8 proteins fold all heterotrimeric G protein alpha subunits, to exploit a Ric-8-based technology to purify recombinant G proteins and to use the G proteins in assays to explore the mechanisms of action of the 33-member adhesion GPCR family or Family B2 GPCRs. We found that adhesion GPCRs are activated by a tethered peptide agonist mechanism that differed from the common example known at the time, protease activated receptors (PARs). PARs have an N-terminal leader sequence that is clipped by exogenous proteases to reveal a new N-terminus that serves as the tethered agonist. Adhesion GPCRs pre-cleave themselves and the two resultant fragments of the receptor remain together to conceal the tethered peptide agonist. Mechanical dissociation of the two fragments aided by protein binding ligands and cell movement serves to decrypt the tethered agonist for binding to its orthosteric site. Our current goals are to explore this mechanism in detail and to understand how it may happen for the 33 adhesion GPCRs in complex physiological contexts…one being our discovery that GPR56 is the platelet receptor that senses collagen and shear force to initiate the platelet activation program. Dr. Tall has been continuously funded by the NIH since receiving an early RO1 award at Rochester. He has continued funding at Michigan through the MIRA R35 program. Dr. Tall has presented his work at 59 invited seminars including national and international meetings and academic departmental seminars. " Dr. Gregory Tall on the web The Tall Lab University of Michigan Google Scholar Twitter 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 >>

<< Back to podcast list Strategic Partner(s) Dr. Raul Gainetdinov About Dr. Raul Gainetdinov Raul R. Gainetdinov is the Institute of Translational Biomedicine Director at Saint Petersburg State University (SPBU), Russia. Before SPBU, Raul R. Gainetdinov was a Senior Researcher in the Department of Neuroscience and Brain Technologies at the Italian Institute of Technology in Genova, Italy (2008-2016) and an Associate Research Professor in the Department of Cell Biology at Duke University in North Carolina, USA (1996-2008). From 2013-2018, he was also a Professor at the Skolkovo Institute of Science and Technology (Skoltech), Moscow. Before joining the Department of Cell Biology in 1996 as a postdoc and becoming faculty at Duke in 2000, he researched at the Institute of Pharmacology Russian Academy of Medical Sciences in Moscow (1988-1996). He received a Ph.D. in pharmacology in 1992 from the Russian Academy of Medical Sciences and an M.D. in 1988 from the Second Moscow Medical Institute, Moscow, Russia. Since 2013, he has been elected Chair of the subcommittee for the Dopamine receptors of the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR). As of August 2022, he has over 270 publications in scientific journals (including Science, Nature, Cell, and PNAS) and co-authored 13 patents. His papers were cited over 28,000 times (H-index – 81, ISI Web of Science). In 2018-2020, Raul R. Gainetdinov was included in the Web of Science (WOS) Highly Cited Researchers (HCR) list, representing the top 0.1% of scientists worldwide. Dr. Raul Gainetdinov on the web Saint-Petersburg State University Wikipedia Google Scholar Researchgate Google 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 >>

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

<< 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 >>

Lin and Ball of GeneTex on GPCR antibody characterization, recombinant monoclonals, five-pillar validation, and the LGR5 challenge. << Back to podcast list Strategic Partner(s) Lin and Ball: GPCR Antibody Characterization and the Recombinant Shift Reliable antibodies are not a convenience in GPCR research - they are the foundation on which every expression and localization experiment rests. Yet the GPCR field has lived with a quiet, persistent problem: antibodies that pass catalog-level QC, ship to a lab, and fail in the only system that matters. This conversation examines that problem from the inside. Chia-Yi Lin and Alexander Ball, both scientists-turned-industry professionals at GeneTex, trace how the commercial antibody landscape has shifted over the past decade - away from polyclonal and hybridoma-based production toward recombinant monoclonal antibodies built around rigorous five-pillar characterization. The conversation covers why GPCR targets are especially difficult to immunize against, how receptor family homology between targets like CXCR1 and CXCR2 makes immunogen selection a critical and underappreciated decision point, and what it actually looks like to validate an antibody against a target as stubborn as LGR5. For Ball, the stakes became concrete years before GeneTex - in a research lab where the reliability of a single antibody determined whether an experiment could move forward at all. That experience runs through this entire conversation. ABOUT THE GUESTS Alexander Ball is a senior scientist at GeneTex who joined the company in 2012 after training in medicine at the University of Southern California and spending years at the research bench, where he worked directly with antibody production and encountered firsthand the variability inherent in polyclonal reagents. At GeneTex, he oversees target selection, QA review, and scientific outreach, and serves as the direct point of contact for GPCR researchers requesting free antibody samples through the Dr. GPCR ecosystem. His dual perspective - having depended on antibodies as a bench scientist and now helping produce them - shapes how GeneTex approaches community collaboration for the GPCR field. Chia-Yi Lin is the head of international sales, marketing, technical support, and logistics at GeneTex International in Taiwan, which she joined in 2016 after completing a PhD in stem cell biology at the University of Edinburgh and a postdoctoral fellowship. Her own experience with GPCR antibody failures during knockout mouse experiments - purchasing commercial antibodies that produced signal where none should exist - gave her an early, direct understanding of what the field was missing. She now leads the programs connecting GeneTex's growing catalog of recombinant GPCR antibodies with the researchers best positioned to characterize them. SCIENTIFIC THEMES OF THE CONVERSATION The GPCR antibody reliability problem - how it developed, why it persists, and what systematic characterization requires Immunogen selection as the critical upstream decision in GPCR antibody development The five-pillar approach to antibody characterization applied to notoriously difficult receptor targets Recombinant monoclonal antibodies as the structural solution to batch variability and reproducibility Researcher-company collaboration as an active ingredient in antibody quality - not a support function Career transitions from bench science to the reagent industry, and what that crossing of worlds makes visible KEY INSIGHTS FROM THE CONVERSATION 1. GPCR Family Homology Makes Immunogen Selection the Deciding Variable Before a single rabbit is immunized, the choice of immunogen has already determined whether a GPCR antibody can succeed. Chemokine receptors like CXCR1 and CXCR2 share over 75% sequence identity - use the wrong peptide region and the resulting antibody is cross-reactive before it leaves production. Ball describes this as the point where most GPCR antibody programs are already lost, long before any downstream characterization begins. 2. LGR5 Became GeneTex's Reckoning with the GPCR Target Class LGR5 - a receptor critical to adult stem cell maintenance in intestinal crypts and implicated in several malignancies - was the target that made the difficulty of GPCR antibody development concrete for GeneTex. Ball recounts his company's president going pale when the subject came up: every commercial antibody they tested failed to meet expectations, and their own early attempts were no more reliable. Years later, GeneTex now has both polyclonal and recombinant monoclonal options for LGR5 - but the process to get there reshaped how the company approaches the entire GPCR category. 3. "Characterized" Is More Honest Than "Validated" - and the Difference Matters The word "validated" implies a finished state that no antibody ever truly reaches. Ball and Lin argue that "characterized" is the more accurate frame - an antibody has been tested in specific applications, against specific cell lines, using specific controls, and those results are known. What is not shown on a data sheet is also information: the absence of a Western blot entry does not mean the experiment was never run. Researchers who understand this read data sheets differently, and ask better questions before purchasing. 4. A Researcher at SFN, a Knockout Mouse, and No Working Antibodies Lin's first antibody conference was SFN in 2018. A researcher approached the GeneTex booth and described his situation: he had knockout mice for the mu opioid receptor, purchased multiple commercial antibodies, and found that several of them produced signal in the knockout - the clearest possible evidence of non-specificity. GeneTex had nothing for that target at the time. But the encounter crystallized the problem Lin had been reading about abstractly: the GPCR research community was spending real time and money on reagents that were quietly producing false results, with no reliable way to know before the experiment was run. 5. Recombinant Monoclonals Solve the Problem Polyclonals Were Never Designed to Solve Polyclonal antibodies are inherently variable: each new production batch is a different rabbit, a different immune response, a different mixture of binding clones. For most targets, that variability is manageable. For GPCRs - which are difficult to express, difficult to immunize against, and require extensive characterization work to pass validation - that variability means that every batch can undo what the previous one demonstrated. Recombinant monoclonal antibodies eliminate this uncertainty: the sequence is defined, stored in a plasmid, and reproducible at any scale, indefinitely. As Ball puts it, the antibody does not run out because a rabbit does. 6. The Most Expensive Thing a Lab Can Waste Is Not Money Ball's most direct recommendation to researchers is to contact the company before buying - not after the experiment fails. The cost of starting with a reagent that cannot do what a project requires is not measured in catalog prices but in the time of students, postdocs, and scientists who run months of experiments before the antibody itself is questioned. GeneTex's approach to the GPCR community - offering free samples for testing in researcher-owned systems - is a direct response to this: the company needs external expert feedback, and the researcher needs a reagent that actually works. 7. What Scientists Who Cross Into Industry Learn That Those at the Bench Cannot Both Ball and Lin arrived at GeneTex from active research positions, and both describe a shift in how they understood antibodies only after making that transition. At the bench, an antibody is a tool you trust or distrust based on results. Inside a company, you understand the full range of decisions - immunogen design, host selection, production format, QC protocol - that determine what a researcher receives. Ball is direct about this: the full gestalt of the antibody world is not visible from the bench, and that gap in understanding contributes to the antibody problems researchers encounter without knowing why. EPISODE TIMELINE Timestamps are AI-generated based on the provided transcript and may vary slightly from the final edited video. Use timestamps as a navigational guide. 00:00 Sponsor message and host intro 00:58 Introducing Lin and Ball - roles and context at GeneTex 03:25 GeneTex history - from a Texas research lab to a global antibody company 05:49 The antibody reproducibility crisis and how GeneTex responded 09:25 Lin's path from stem cell biology PhD to leading antibody characterization programs 12:20 Ball's path from medical school to the research bench to GeneTex 14:38 The scientists who founded GeneTex and the scientific problems that shaped the company 16:49 LGR5 - the GPCR that exposed how deep the antibody quality problem runs 19:21 A researcher walks up at SFN with knockout mice and no working antibodies 21:49 What researchers get wrong with antibody selection - and what to ask instead 25:00 Five-pillar characterization in practice - KO lines, comparable antibodies, GPCR arrays 30:19 Recombinant monoclonals vs. polyclonals - what changes for GPCR research 36:55 If not antibodies - Ball and Lin on the power of scientific communication 39:40 The GPCR therapeutic market and what remains untapped SELECTED QUOTES "Making antibodies, of course, needs some technique. But to verify them - to characterize them, to validate them - it actually takes more effort. And that has to be based on science." Chia-Yi Lin "If you don't choose the immunogen properly, you're already messed up. You're doomed before you even shoot a rabbit." Alexander Ball "You really don't understand antibodies until you're in the industry. I think people at the bench haven't had that experience. You really get it once you're actually in the industry." Alexander Ball "It's defined by the primary sequence. It's there. It's in a plasmid. It's not going away. It's inexhaustible." Alexander Ball, on recombinant monoclonal antibodies 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) Murat Tunaboylu & Ben Holland About Murat Tunaboylu "Murat Tunaboylu, Antiverse's CEO, has a software engineering and bioinformatics background. Mid-career, he has worked in finance and developed high-frequency trading systems. After switching to biotech, Murat has built cell imaging software and lab robots to accelerate cancer research and automated Thermo Fisher Scientific’s gene synthesis workflows. He has co-founded consultancy and biotech companies Svarlight and Antiverse. His current focus is to realise Antiverse’s mission: engineering the future of drug discovery." Murat Tunaboylu on the web Antiverse DSV Future of Drug Discovery Podcast Twist Bioscience LinkedIn Twitter Dr. GPCR About Ben Holland "Ben gained his masters in Engineering Science from Oxford, taking a specialisation in information engineering. Following this, he joined an early-stage medical device start-up and in 5 years was responsible for project R&D and managing a focused development team, pursued international strategic partnerships, managed IP matters, helped establish a manufacturing line in Malaysia and is named as inventor on several patents. He then returned to information engineering and has been working in machine learning for nearly 10 years, applying it to antibody generation, analysis, and property prediction since 2017" Ben Holland on the web Antiverse The Antibody Society YT LinkedIn Twitter 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 >>

<< 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 >>

Dr. Amynah Pradhan on why mu opioids worsen migraine, why delta agonists may relieve it, and how chronic disease states rewrite drug discovery. << Back to podcast list Strategic Partner(s) Amynah Pradhan: The Delta Opioid Receptor and the Migraine Paradox Chronic migraine sits at a peculiar crossroads in opioid pharmacology: sustained mu opioid receptor activation is a well-documented driver of medication-overuse headache, while preclinical evidence points to delta opioid receptor agonism as a candidate to relieve the same disorder. Dr. Amynah Pradhan's lab at the University of Illinois at Chicago has spent years pulling apart that asymmetry — combining mouse models of chronic migraine, cortical spreading depression, and opioid-induced hyperalgesia with peptidomic screens and conditional genetics to ask where the two receptors diverge anatomically, pharmacologically, and in the chronic disease state. The work sits inside a larger argument Dr. Pradhan returns to often: that organisms in chronic pain are fundamentally different biological systems than naïve ones, and that drug discovery fails when it pretends otherwise. For her, this line of work is also personal — the delta opioid receptor has been her scientific focus for nearly two decades, through failed clinical trials in depression and pain, and migraine may finally be where it finds a clinical home. About the Guest Dr. Amynah Pradhan is Associate Professor of Psychiatry at the University of Illinois at Chicago, where her lab studies opioid receptor biology in the context of headache disorders, chronic pain, and their comorbid emotional states. She trained in pharmacology at McGill University with Paul Clarke and completed postdoctoral work at AstraZeneca, with Brigitte Kieffer in Strasbourg, and with Chris Evans at UCLA. Her research integrates behavioral pharmacology, ligand-directed signaling, and mouse models of migraine, and has become central to the small community of basic pharmacologists working inside the headache field. Scientific Themes of the Conversation The mu/delta asymmetry in migraine — why two receptors in the same family produce opposite clinical outcomes Chronic disease states as fundamentally altered biological systems — and what that means for drug discovery Ligand-directed signaling and receptor trafficking — how internalization shapes tolerance and adverse effects The emotional circuitry of chronic pain — and the kappa opioid / dynorphin link The unfinished GPCR frontier — PACAP, CGRP, and the persistent antibody problem Career mobility through collaboration — how a headache neurologist redirected two decades of work Key Insights from the Conversation The yin-yang that organizes the lab. Mu opioid agonists, in chronic use, exacerbate migraine and drive medication-overuse headache. Delta opioid agonists appear to relieve the same symptoms — pain, negative affect, and aura-related signs in preclinical models. Dr. Pradhan treats the contrast not as a side story but as the organizing question of her work. Chronic states are not scaled-up acute states. One of Dr. Pradhan's recurring arguments is that the organism in a chronic disease state is fundamentally altered, and that drug candidates fail in clinical trials partly because they are validated in naïve animals that do not resemble the patients they will eventually treat. Internalization is a design choice, not a side effect. Earlier work in her career showed that high-internalizing delta agonists drive receptor downregulation and tolerance, while low-internalizing agonists uncouple the receptor from ion channels without losing it. The ideal delta agonist, by her account, would be non-internalizing, brain-penetrant, long-half-life, and directed at forebrain circuits where emotional salience of pain lives. Delta agonists may finally have a disease. After failed trials in depression and pain, Dr. Pradhan argues that migraine — with its emotional comorbidity, its anatomical overlap with delta receptor expression, and its distinctive pain mechanisms — may be the clinical home the compound class has been looking for. The conviction is quiet but deeply held. The antibody problem is keeping a field from basic answers. Her "bugaboo": we still do not know reliably where many GPCRs live — which cell type, which compartment, surface versus intracellular — because antibodies for the family are widely unreliable. For a pharmacologist, the resolution problem sits upstream of every other question. A single collaboration can redirect a career. Her move from pure opioid pharmacology into migraine came from sharing a building with neurologist Andrew Charles at UCLA. She treats this as a generalizable lesson for junior scientists: openness to collaboration is not decorative — it is how fields get rewired. The invisible labor of being the only one in the room. Toward the end of the conversation, Dr. Pradhan turns to the structural weight carried by women and scientists of color in academia — the cumulative load of committee service, mentorship, and representation — and argues that real support requires institutions to account for it, not just request it. Episode Timeline Timestamps were generated using AI for readability. 00:00 Introduction 01:13 From McGill to migraine — a path through four labs 04:19 Why mu worsens migraine and delta relieves it 09:27 What chronic dosing does to the receptor — tolerance, internalization, downregulation 14:17 Designing the delta agonist she wants 17:30 The emotional circuitry of chronic pain — and the kappa link 22:22 CGRP, PACAP, and why GPCR drug discovery is not out of runway 28:54 Biased ligands after the hype cooled 34:08 How you measure migraine in a mouse 40:44 Three aha moments — and why delta agonists may finally have a home 43:28 The hidden cost of being the only one in the room 57:05 What the pandemic did to a mouse colony Selected Quotes "The delta opioid receptor is my baby. I've been working on it for almost 20 years under lots of different contexts." "The organism is fundamentally altered in a chronic disease state. They're not in the same state as they were if they were naïve. Patients didn't come to the doctor to look for drugs because they were feeling fine." "Every person I know who studies G-protein coupled receptors will tell you — the antibodies suck. We're still arguing about where the receptor is. What cell type it's on. Is it on the cell surface? Is it inside the cell? The fact that we can't say that is kind of crazy to me." "Maybe the disease state where delta ligands would really be effective would be in headache disorders — in migraines specifically. Maybe this is where it all comes together." About this episode In this episode of the Dr. GPCR podcast , we meet with Dr. Amynah Pradhan. She is an Associate Professor of Psychiatry at the University of Illinois at Chicago. Amynah did her undergrad research measuring IP3 in airway smooth muscle cells and completed a Ph.D. at McGill University in Canada with Dr. Paul Clarck , where she studied opioid receptors. Her next career step took her to AstraZeneca as a postdoctoral trainee, where she studied animal models of pain and sensory neuron sensitive-receptor. She then returned to academia and worked on opioids as a postdoctoral trainee with Dr. Brigitte Kieffer , where she studied ligand-directed signaling at the delta-opioid receptor. Her career path-defining moment came from a third postdoctoral experience with Dr. Chris Evans at UCLA. Amynah studied how arrestins regulate ligand-directed signaling at delta-opioid receptors, and it is their collaboration with a headache physician-scientist Dr. Andrew Charles that who specialized in animal models of migraine and delta-opioid receptors as a therapeutic target to treat headache. Dr. Amynah Pradhan on the web Lab page LinkedIn Twitter Google Scholar 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 >>

mGlu2 can suppress drug seeking across four addictive substances - but its clinical results have never been published. Johnson explains why the circuit matters more than the receptor. << Back to podcast list Strategic Partner(s) Kari Johnson: mGlu2, Addiction, and the Brain Circuits Alcohol Rewires The brain circuits governing reward, motivation, and decision making are not fixed - they are continuously reshaped by experience. In alcohol use disorder and other substance addictions, one of the most consequential changes is the shift from goal-directed to habitual behavior: a state in which drug seeking persists not because of pleasure, but because the underlying circuit no longer responds to consequences. mGlu2, a presynaptic metabotropic glutamate receptor coupled to Gi/o proteins, sits at a critical junction in this process. By suppressing glutamate release across circuits in the basal ganglia, mGlu2 is positioned to modulate drug seeking, habit formation, and reward processing - and has been pursued as a potential therapeutic target in addiction, depression, schizophrenia, and Parkinson's disease. Kari Johnson's research follows this receptor from the bench to the behaving animal, using optogenetics and circuit-selective mouse models to ask which specific corticostriatal pathways are driving behavioral change after alcohol exposure - and whether pharmacological rescue is possible after those circuits have already been disrupted. The question has been central to Johnson's career since long before the tools to answer it properly existed. ABOUT THE GUEST Kari Johnson is an assistant professor of neuropharmacology at the Uniformed Services University of Health Sciences in Bethesda. Her lab investigates how GPCRs modulate synaptic transmission in brain circuits involved in reinforcement learning, with a particular focus on how chronic alcohol exposure disrupts those mechanisms across levels ranging from gene expression to neural circuit function to behavior. She trained in high-throughput drug discovery at Vanderbilt - contributing to early functional assay development for metabotropic glutamate and muscarinic receptors - before completing postdoctoral training at the National Institute on Alcohol Abuse and Alcoholism with Dave Lovinger. Her current work combines whole-cell patch clamp electrophysiology, optogenetics, and operant behavioral pharmacology to study mGlu2 function in specific corticostriatal circuits and its role in the transition from controlled to compulsive drug use. SCIENTIFIC THEMES OF THE CONVERSATION mGlu2 as a convergence target across addiction, psychiatric disease, and movement disorders Circuit-specific GPCR modulation and the "modulomics" framework Goal-directed versus habitual behavior as a mechanistic framework for understanding addiction Pharmacological rescue of alcohol-disrupted receptor function using positive allosteric modulators The translational gap: why a decade of preclinical mGlu2 evidence has not yet reached clinical success The limits of brain slice electrophysiology - and why optogenetics redefines the questions the field can ask KEY INSIGHTS FROM THE CONVERSATION mGlu2 Sits at the Center of Multiple CNS Disorders Because mGlu2 regulates glutamate release in brain regions linked to reward, executive function, motivation, and stress responses, it has become a target of interest across an unusually broad disease landscape - alcohol use disorder, schizophrenia, depression, Parkinson's disease, and multiple other substance addictions. That breadth is a signal of the receptor's centrality in CNS function. It is also a complication: a receptor that modulates so many circuits will inevitably produce wanted and unwanted effects that are difficult to predict from any single experimental system. Alcohol Disrupts mGlu2 - But a PAM Can Restore It Johnson's lab demonstrated that adolescent alcohol exposure disrupts mGlu2 function in the striatum in a way that might seem to close off therapeutic targeting - if the receptor is impaired, can it still be activated pharmacologically? Their answer was yes: a positive allosteric modulator restored mGlu2 signaling even after alcohol-induced disruption. This finding shifts the question from whether mGlu2 is a viable target in addiction to how to reach it once its function has already been compromised. The Years Before the Tools Existed For most of the history of GPCR electrophysiology, researchers used electrical stimulation in brain slices and could observe that a receptor modulated synaptic transmission - but not which specific set of synaptic inputs was responsible. For Johnson, this was a formative constraint she navigated across her entire training: drawn to circuit-level questions that her early tools could not fully answer, she made the shift to optogenetics and genetically defined neuronal populations specifically because the biology demanded it. The tools arrived late relative to the questions. That gap, in Johnson's framing, is both a limitation of the past and an argument for the field's current momentum. Modulomics: Naming the Question Changes What You Can Ask Johnson's postdoc mentor Dave Lovinger coined the term "modulomics" to describe the systematic study of circuit-specific neuromodulation by GPCRs - using light-activated ion channels expressed in anatomically or genetically defined neurons to isolate receptor effects at individual synaptic inputs rather than across an entire stimulated pathway. Giving the approach a name formalizes it as a research program, not just a technique. Johnson's lab has extended this using conditional knockout mice that allow selective deletion of mGlu2 from specific cell types, enabling circuit-level pharmacology with direct behavioral readouts. The Habit Framework Changes What Addiction Means Pharmacologically The shift from goal-directed to habitual behavior is not just a behavioral description of addiction - it implies a specific circuit mechanism. Goal-directed behavior is sensitive to changes in outcome value; habitual behavior is not. When alcohol exposure biases the brain toward habit formation, the circuit underlying that inflexibility becomes the pharmacological target. Johnson's lab uses this framework to ask whether activating mGlu2 in specific corticostriatal circuits can reverse the habit bias that chronic alcohol produces - not just dampen the pleasure of drinking, but restore the flexibility of the decision that precedes it. Clinical Trial Results for mGlu2 Ligands Have Not Been Made Public Johnson noted that multiple clinical trials testing mGlu2 ligands in substance use disorders - including for smoking cessation and cocaine use disorder - have been conducted and completed. The results have not been released to the research community. Without access to those data, researchers cannot determine why promising preclinical findings did not translate, cannot adjust future trial designs, and cannot evaluate whether the receptor was genuinely ineffective or whether confounds such as prior antipsychotic exposure were responsible - a hypothesis already supported by subsequent preclinical work following the disappointing schizophrenia trials. The gap is consequential, and Johnson named it directly. Translating GPCR Research May Require Releasing Attachment to Specific Receptors One of Johnson's more quietly contrarian observations is that attachment to a "favorite receptor" may be limiting translational success. If mGlu2 activation produces the desired circuit effect in rodents but not in humans, the value of that work is not lost - it defines the functional target. A different receptor capable of achieving the same circuit-level effect in a human brain might carry the therapy further. The question, in Johnson's framing, is not which receptor you prefer, but which receptor is correctly positioned in the human circuit you need to modify. EPISODE TIMELINE Note: Timestamps are AI-generated from the transcript and may require manual verification after video editing. 00:00 Introduction 01:27 Johnson's career path - from Vanderbilt drug discovery to NIH postdoc to independent lab 07:31 Alcohol disrupts mGlu2 in adolescent mice - and a positive allosteric modulator rescues it 09:45 Why mGlu2 is Johnson's receptor of focus: synaptic plasticity and long-term depression 11:26 mGlu2 and drug seeking: preclinical evidence across alcohol, cocaine, methamphetamine, and heroin 13:28 How mGlu2 modulates dopamine release and the neurobiology of habit formation 16:28 Optogenetics and modulomics - studying circuit-specific GPCR function in the basal ganglia 20:45 Operant behavioral models: how habit formation is measured in mice 25:25 Clinical trials for mGlu2 ligands - what advanced, what disappointed, and what remains unpublished 28:41 Are GPCRs still good drug targets? A circuit-level argument 33:12 Advice for junior scientists: let the biology lead the method 35:28 Diversity in STEM and who carries the labor of change SELECTED QUOTES "Even if we see that these experiences cause an impairment in receptor function, there might be pharmacological strategies that we can use to rescue that." "We're really just beginning to scratch the surface of understanding how these receptors work in specific neural circuits - and that has the potential to impact our understanding of how they influence a really wide range of behaviors, especially since mGlu2 is expressed in so many different brain areas." "Maybe the effect that I want to have by activating mGlu2 has the effects I want in a rodent brain, but doesn't have it in a human brain. But maybe there's another receptor there that will have the effect that we want in the human brain." "Let the science lead you. If you take that approach, you'll have plenty of moments where you realize that a new tool could take your research to another level. But there's no reason to force it just because you feel like you should be incorporating a popular technique." About this episode Dr. Kari Johnson is currently an assistant professor at the Uniformed Services University of the Health Sciences in Bethesda, Maryland. She is a neuropharmacologist with an interest in the long-term effects of alcohol abuse on neural circuits. Kari completed her Ph.D. in Pharmacology at Vanderbilt University before continuing her training as a postdoctoral fellow at the Vanderbilt Center for Neuroscience Drug Discovery, the National Institute of General Medical Sciences, and the National Institute on Alcohol Abuse and Alcoholism. All through her career, the recurring theme in Kari’s work has been GPCRs and more specifically Metabotropic Glutamate Receptors. Join me and learn more about how Kari studies GPCRs in basal ganglia circuits following chronic alcohol exposure in mice. Dr. Kari Johnson on the web LinkedIn Google Scholar Research Gate USU Twitter 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. Nicola J. Smith About Dr. Nicola J. Smith Dr. Nicola J Smith is an expert in molecular pharmacology with a track record in exploring GPCR structure-function relationships in the context of cardiovascular disease and metabolic disorders. She is a National Heart Foundation of Australia Future Leader Fellow and runs a laboratory of 7 Ph.D. and Honours students at UNSW Sydney, where she has recently been promoted to Associate Professor. Most recently, Dr. Smith’s team has made advances in the understanding of how an orphan GPCR exerts its effects both in vitro (cell culture and ex vivo models) and in vivo (measures of physiological and pathological cardiometabolic function in unconscious and conscious mice). Together with Irina Kufareva , UCSD, her team developed a novel approach to identifying ligands for orphan GPCRs by developing a powerful new computational tool for identifying ‘surrogate’ ligands (borrowed from other receptors) for orphan GPCRs, named GPCR-CoINPocket. Her career goal is to leverage this expertise to establish a research program that takes orphan GPCRs from ‘locked’, inaccessible receptors to well-characterized and understood ‘unlocked’ therapeutic targets with high-affinity ligands. Dr. Nicola J. Smith on the web UNSW Sydney LinkedIn Retraction Watch Twitter 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. Josephine (Pina) Cardarelli About Dr. Josephine (Pina) Cardarelli Dr. Pina Cardarelli, CSO for GPCR Therapeutics Inc., based in South Korea, has recently been named President of GPCR Therapeutics, USA, a newly incorporated Biotechnology company in the Bay Area. The company’s mission is to discover and develop highly effective cancer therapeutics by targeting heteromers of G protein-coupled receptors (GPCR). Burixafor, their most advanced clinical candidate, will be in Phase II clinical trial next year. Additionally, they have a library of target GPCR heteromers for Oncology. Dr. Cardarelli heads the team of talented researchers that will be expanding at the US site. Dr. Cardarelli is a drug development leader with extensive experience driving drug discovery teams in bringing biologics to clinical proof of concepts. She has expertise in cell biology, pharmacology, translational medicine, oncology, immuno-oncology, immunology, and clinical development. Previously, she held the position of Vice President of Cell Biology & Pharmacology, at Bristol-Myers Squibb . She was an integral contributor to two therapeutics that are FDA approved, Yervoy and Opdivo. She was a participant in numerous due diligence (anti-CXCL8 mAb) and has managed external collaborations and alliances. Prior to this, she held the position of Vice President, at Medarex, Inc . While at BMS and Medarex, she led programs from target ID to clinical development that included, CXCL10 (Eldelumab), CXCR4 (Ulocuplumab), CD30, CD19, Fucosyl GM-1, & mesothelin-ADC, Glypican-3-ADC, CD70-ADC. She oversaw early discovery programs IL-23 p19 and IL23 p19/IL-17 bispecifics. At Medarex, she initiated and identified the lead mAb for the type I interferon-alpha receptor project, licensed to AstraZeneca (Saphnelo™ Anifrolumab) that has just received FDA approval for systemic lupus erythematosus. She has extensive experience working with Biologics, and Antibody Drug Conjugates as well as experience in IND fillings, IB updates, and responding to FDA inquiries. She is an inventor on 39 issued U.S. patents including anti-PD-1 patents, 22 EP patents, and greater than 100 global patents centered around therapeutic development. She has also authored forty-six peer-reviewed publications. Dr. Cardarelli received her Ph.D. in Physiology from Albany Medical College. Dr. Josephine (Pina) Cardarelli on the web LinkedIn Company Website 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. Neil Grimsey About Dr. Neil Grimsey " During my postdoctoral studies at USCD, I discovered a novel GPCR-dependent atypical kinase activation mechanism that drives vascular edema and inflammation. These studies shaped my future goals as an Assistant Professor in the College of Pharmacy at the University of Georgia Athens. My group studies the spatiotemporal dynamics of atypical inflammation and the control of disease progression. We have developed an array of fluorescent biosensors to map kinase activity in living cells and are exploring innovative techniques to delineate the molecular dynamics of atypical p38 and suppress kinase activation. To further define the role of atypical p38 signaling responses we are studying how atypical p38 controls the onset and pathogenesis of acute lung injury, retinal vasculopathies, and infections. " Dr. Neil Grimsey on the web LinkedIn University of Georgia Google Scholar X (Twitter) 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 >>

<< 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. Daniel Isom About Dr. Daniel Isom "Dan was born and raised in the Cleveland area. He is a first-generation college graduate and academic. After spending two years at the Cleveland Institute of Art, he earned degrees in Biochemistry and Chemistry from Case Western Reserve University. He then went on to earn a Ph.D. in Molecular Biophysics from Johns Hopkins University, followed by postdocs at both Duke University and UNC Chapel Hill. Dr. Isom was recruited to the Molecular and Cellular Pharmacology Department at the University of Miami Miller School of Medicine in 2016, where he is currently a practicing molecular pharmacologist and biophysicist, systems and synthetic biologist, technologist, heavy CRISPR user, protein sequence- and structure-based informaticist, computational geometer, virtual screener, and Python, medical, and graduate educator leading a talented and multidisciplinary research team. " Dr. Daniel Isom on the web Isom Lab University of Miami Miller School of Medicine LinkedIn X (Twitter) BlueSky 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 >>

Hay on class B GPCRs, RAMPs, and the selectivity problem in CGRP-targeted migraine therapies - what the approved drugs may still be getting wrong. << Back to podcast list Strategic Partner(s) Debbie Hay: Class B GPCRs, RAMPs, and the Migraine Pharmacology Gap Class B GPCRs represent one of the smaller subfamilies in the GPCR superfamily - just 15 receptor genes - yet they govern a disproportionately wide range of physiology, from calcitonin-mediated bone remodeling to the peptide signaling networks underlying migraine. Their pharmacological complexity is amplified by receptor activity modifying proteins (RAMPs), three single-pass membrane proteins that associate with these receptors to create pharmacologically distinct complexes. A single receptor can form three different functional units depending on which RAMP is present, and those distinctions determine ligand selectivity, signaling output, and ultimately drug targeting. Hay examines the molecular pharmacology of the calcitonin receptor and calcitonin-like receptor - with particular focus on their RAMP-dependent behavior and their roles in CGRP-mediated migraine. She argues that the field has moved faster than the evidence warrants: approving antibodies and small molecules against receptor targets whose full selectivity profile remains uncharacterized. For Hay, who has studied RAMPs since they were first described and when working on them was a high-risk research bet, the CGRP drug approvals are both a vindication and a reminder of how much foundational pharmacology the field skipped on the way to the clinic. ABOUT THE GUEST Hay is a professor of pharmacology at the University of Otago, New Zealand. Her research centers on the molecular pharmacology of class B GPCRs - specifically the calcitonin receptor and calcitonin-like receptor - and their interactions with RAMPs. She has worked across pharmaceutical, biotechnology, and academic settings, including a research placement at GlaxoWellcome, a PhD in molecular pharmacology at Imperial College London, and 17 years at the University of Auckland, where she led her own laboratory and served as head of department. Her current work addresses one of the central unsolved problems in RAMP pharmacology: developing tools selective enough to distinguish between closely related receptor-RAMP complexes in disease-relevant tissues. SCIENTIFIC THEMES OF THE CONVERSATION RAMP-dependent pharmacological diversity in class B GPCRs The selectivity problem in CGRP-targeted migraine therapies Obligatory receptor heterodimers and the limits of current characterization tools Structural biology of RAMPs - allosteric modulation over direct ligand contact Reproducibility and target validation as prerequisites for meaningful GPCR pharmacology Career navigation across academia, big pharma, and biotech KEY INSIGHTS FROM THE CONVERSATION Fifteen Genes, Far More Than Fifteen Pharmacologies Class B GPCRs are a small family by gene count, but RAMP association multiplies their pharmacological diversity considerably. Each of the three RAMPs can pair with a given receptor to produce a distinct complex - different ligand selectivity, different signaling profile, different therapeutic implications. The field routinely treats these complexes as interchangeable, but Hay argues they are not, and that assumption has downstream consequences for how drugs are characterized and how trial failures are interpreted. The Erenumab Selectivity Problem Erenumab, the first monoclonal antibody approved against a GPCR complex, targets the CLR-RAMP1 receptor - the canonical CGRP receptor in migraine. But Hay makes the case that the antibody's selectivity for this complex over the closely related CTR-RAMP1 complex has never been adequately demonstrated. Shared structural features between the two receptor complexes, combined with the known pharmacology of CGRP at CTR-RAMP1, suggest the drug may be less target-selective than its approval label implies - and that effects attributed to one target may partly involve another. mRNA Cannot Tell You Where the Functional Dimer Is For obligatory heterodimers like RAMP-receptor complexes, knowing which component genes are expressed in a cell tells you surprisingly little. The functional unit is the assembled complex at the cell surface, and that assembly is not predictable from transcript data - even at single-cell resolution. Hay frames this as one of the foundational unsolved problems in RAMP pharmacology: without tools to visualize and quantify the actual complex in native tissue under disease conditions, target validation remains incomplete and the pharmacology remains unresolved. RAMPs Act Allosterically - Not Through Direct Ligand Contact Structural data from the CLR and CTR receptor families has produced a result that surprised the field: RAMPs contribute almost no direct molecular contacts to the bound ligand. Their influence on receptor pharmacology appears to be primarily allosteric - subtly reshaping the GPCR binding site rather than contributing their own contact surface. This reframes the design challenge for RAMP-selective compounds: the differences between receptor complexes are conformational and fine-grained, not structurally obvious, making ligand selectivity considerably harder to engineer than a direct-contact model would predict. The Migraine Pharmacology Gap CGRP is elevated in migraine, infused CGRP triggers migraine-like headache in susceptible individuals, and drugs targeting that pathway can abolish chronic migraine entirely for some patients - while doing nothing for others. The mechanistic story remains incomplete: which receptor complex mediates which symptom, why the response is so variable across patients, and what the CGRP system is actually doing in the peripheral and central nervous system. For a condition affecting up to 20% of women worldwide, Hay notes, the research investment in understanding the receptor-level biology is strikingly insufficient. Burning Curiosity as the Non-Negotiable Hay's advice to junior scientists distills to a single criterion: if the curiosity isn't deep enough to outlast the failures, the career won't hold. Grant rejections, papers rejected seven times, experiments that don't replicate - these are not exceptional events but structural features of a scientific life. The scientists who persist, in her framing, are not the ones who feel less pain from those setbacks, but the ones for whom the pull toward the question is stronger than the push of the failure. She gives herself one day to be unhappy about a rejection. Then she moves on. EPISODE TIMELINE Timestamps are AI-generated from the episode transcript and are approximate. Minor offsets may occur in the final edited episode. 00:00 Welcome and episode announcements 01:40 Introduction - Hay 02:43 Career trajectory - from vet school to GPCR pharmacology 07:55 First encounter with GPCRs at GlaxoWellcome - and how RAMPs entered the picture 11:03 Class B GPCRs - why 15 receptor genes produce far greater pharmacological diversity than expected 13:30 CGRP, migraine, and the first antibody approved against a GPCR complex 18:50 Migraine as an invisible disability and the limits of what current treatments explain 20:41 Obligatory dimers and the challenge of mapping receptor complexes in disease-relevant tissue 23:54 Tools the field needs - antibody selectivity, selective ligands, and bimolecular fluorescence complementation in vivo 26:42 Structural data and what it reveals about how RAMPs actually modulate receptor pharmacology 29:43 Are GPCRs still good drug targets - and what is missing from class B pharmacology 31:41 Reproducibility, target validation, and the cost of science that cannot be repeated 34:53 Career advice - burning curiosity, celebrating wins, and being kind SELECTED QUOTES "I can't pick a favorite because these are such complex receptors and we fundamentally don't understand which are most important. Because we don't have selective ligands." "We have to know where our receptor is in our tissue of interest, in our disease condition, and how it is signaling - because that is what we need to target." "There is too much out there that is not replicable. And it causes careers to die. It's just not fair on the junior scientists who then follow up on that work to find it can't be repeated." "If you've got that deep, deep drive still to get over those failures and pick yourself up, and that's a strong enough fire burning, then you will succeed." About this episode Dr. Debbie Hay is presently a professor at the Department of Pharmacology and Toxicology at the University of Otago after spending 18 years at the University of Auckland. Her work is primarily focused on class B GPCRs and their interactions with RAMPs. Debbie obtained a Ph.D. in Molecular Pharmacology from Imperial College London in the UK. She has gained experience from working in academia and at GSK as an industrial trainee. Join me and learn more about Debbie’s career and what she learned through her experiences as a scientist. Dr. Debbie Hay on the web LinkedIn Wikipedia University of Otago University of Auckland Google Scholar Pubmed Research Gate Twitter 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. Evi Kostenis About Dr. Evi Kostenis "Pharmacist by training - PhD in Pharmacology - Postdoc at the NIH with Dr. Juergen Wess - Postdoc and Group leader in Aventis, now Sanofi, Frankfurt, Germany - Head of in vitro Pharmacology at 7TM Pharma in Denmark; Full professor, department chair and director of the institute for pharmaceutical Biology at the University of Bonn. Research interests: Signaling mechanisms involving GPCRs and heterotrimeric G proteins" Dr. Evi Kostenis on the web University of Bonn 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 >>

<< Back to podcast list Strategic Partner(s) Dr. Stephen Ferguson The History of the Great Lakes GPCR Retreat with Dr. Stephen Ferguson About Dr. Stephen Ferguson Dr. Stephen Ferguson is a Professor in the Department of Cellular and Molecular Medicine at the University of Ottawa. He did B.Sc. in biology at McGill University and received his Ph.D. under the mentorship of Dr. Brian Collier in the Department of Pharmacology and Therapeutics at McGill University (1994). He did his postdoctoral training with Dr. Marc G. Caron at Duke University (1994-1997), where he and his colleagues investigated the role of G protein-coupled receptor kinases and beta-arrestin in regulating G protein-coupled receptor endocytosis, trafficking, and signaling. He has held four Canada Research Chairs since 2001 and was previously a Heart and Stroke Foundation of Canada MacDonald Scholar (1998-2003) and Heart and Stroke Foundation of Ontario Career Investigator (2003-2016). He was a recipient of Canada's Top 40 under 40 award in 2004 and received Queen Elizabeth II, Diamond Jubilee Medal, in 2012. He has also received both Junior (2001) and Senior (2005) investigator awards from the Pharmacological Society of Canada. Most recently, in 2021, he was elected as a Fellow of the Canadian Academy of Health Science (FCAHS). His research career has focused on the investigation of the regulation of G protein-coupled receptors signaling mechanisms in health and disease. He currently holds multiple research grants from the Canadian Institutes of Health Research (CIHR) for his research investigating the role of metabotropic glutamate receptor signaling in Huntington’s and Alzheimer’s disease. Dr. Stephen Ferguson on the web Carlton University Canada Research Chairs Twitter ResearchGate LinkedIn Dr. GPCR Ecosystem Great Lakes GPCR Retreat on the web 21st Great Lakes GPCR Retreat More about previous GPCR Retreat meetings 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 >>

Bender uses virtual docking to find chemical probes for orphan GPCRs - receptors biology can't study because the tools don't exist yet. << Back to podcast list Strategic Partner(s) Brian Bender: Computational Probes for Orphan GPCR The GPCR superfamily contains hundreds of receptors that cannot be experimentally studied because no usable chemical probe exists for them. Finding an endogenous agonist - when one is even known - is rarely sufficient: a large peptide or lipidated compound may activate a receptor in vivo but is useless as a cell-based tool. This gap is one of the defining bottlenecks in receptor pharmacology, and closing it one receptor at a time will take decades. Brian Bender's work addresses this problem computationally. At UCSF, he develops structural models of GPCRs using sparse experimental data - combining restraints from X-ray crystallography, NMR, and electron paramagnetic resonance spectroscopy - and applies large-scale virtual docking to identify candidate chemical probes across the understudied GPCR landscape. His approach scales across the family rather than stopping at individual targets. Bender trained at the bench before moving fully into computation, and that transition was not planned. A stalled labeling project on the NPY2 receptor during his PhD at Vanderbilt redirected his entire trajectory - and eventually revealed that the patterns connecting receptors across the GPCR family were more interesting than any single structure. ABOUT THE GUEST Bender is a postdoctoral fellow at UCSF working at the intersection of computational structural biology and receptor pharmacology. His research focuses on predicting GPCR structural ensembles from limited experimental data and using virtual docking to identify chemical probes for orphan and understudied receptors. He trained as a structural biologist at Vanderbilt University, working with X-ray crystallography, protein NMR, and electron paramagnetic resonance before transitioning to computation during his PhD work on the NPY2, NPY1, and ghrelin receptors. His fluency in both bench and computational languages shapes how he builds models and how he interprets the experimental data that constrains them. SCIENTIFIC THEMES OF THE CONVERSATION Computational structural modeling of GPCRs from sparse and low-resolution experimental data Virtual docking as a strategy for pan-GPCR chemical probe discovery The orphan receptor problem - why endogenous agonists are not sufficient tool compounds Bench-to-computation transitions and what fluency in both languages enables Family-wide approaches to receptor pharmacology versus single-receptor studies Building scientific community at the early-career stage KEY INSIGHTS FROM THE CONVERSATION The probe gap is a biological bottleneck, not just a chemical one Without a usable chemical probe, a GPCR cannot be studied pharmacologically in a cell-based setting. Even when an endogenous agonist is known, it may be a large peptide or lipidated compound that cannot be practically dosed in vitro. Bender's work targets this gap directly - arguing that de-orphanizing a receptor biochemically and making it experimentally tractable are two separate problems. Virtual docking changes the scale equation Individual bench approaches to identifying tool compounds can take months to years per receptor. Virtual docking screens compress that timeline significantly and can be applied across many receptors in parallel. Bender frames this not as a replacement for bench pharmacology but as the only realistic path to coverage across the full orphan GPCR landscape. The failed experiment that built a career Bender's NPY2 labeling project - designed to generate DEER spectroscopy distance restraints for conformational modeling - never yielded usable data. Rather than a setback, it became a forced pivot into computation at precisely the moment his modeling skills were becoming sufficient to carry a project independently. The stalled experiment was the origin point of the approach he now applies at family scale. Bench experience as a modeling guardrail Knowing what an EC50 means experimentally, or what a Bmax implies about receptor expression, changes how computational restraints are built and applied. Bender credits his time at the bench with preventing the kind of over-interpretation that models built purely from computational intuition can produce - a perspective that shapes how he translates collaborators' data into structural constraints. The eureka of the whole family Months of manually reading sequence alignment tables - before Bender could write the scripts to automate the analysis - produced an unexpected result: structural and sequence patterns connecting receptors across GPCR subfamilies that he had not been told to look for. That period of laborious, close-range data inspection became the conceptual foundation of his pan-GPCR approach, and the moment he understood that one receptor was not enough. Connecting scientists is its own form of science Bender's role co-chairing the Gordon Research Seminar on Molecular Pharmacology is not separate from his scientific work - it is continuous with it. He articulates that the lateral connections formed at early-career conferences, between people who will be colleagues for the next 20 years, are a different kind of scientific output but no less consequential for where the field goes next. EPISODE TIMELINE Timestamps generated with AI assistance and are approximate. They may vary slightly from the final edited version. 00:00 Introduction 01:31 From structural biology to GPCR computation - how the path began 05:47 Modeling GPCR conformational ensembles from sparse data 07:44 Origin moment - a lab notebook at age 8 11:53 The NPY2 labeling project that stalled - and the pivot it forced 17:22 From NPY2 to ghrelin - when one receptor becomes a family question 19:54 Joining UCSF and building the pan-GPCR docking pipeline 21:53 Co-chairing the Gordon Research Seminar on Molecular Pharmacology 47:42 Why orphan receptors need chemical probes, not just endogenous agonists 52:54 Bench fluency as a guard against over-interpreting computational models 58:16 Advice for early-career scientists on connecting with the field 01:02:48 Eureka moment - patterns across the whole receptor family, read by eye SELECTED QUOTES "Are they crazy? Do they know the gold mine that they just gave me?" "It's hard to ever leave the GPCR world once you go into it, just because the longer you stay in it, the more you realize we still don't know in this family." "Taking time to think about what you're doing is way more valuable than just trying to do the next ten million experiments all at once." "I have to go into more receptors. I can't stay with just the one." About Dr. Brian Bender Dr. Bender completed his undergraduate studies at Colgate University in upstate New York with a degree in Biochemistry. Between undergraduate and graduate school Brian worked as a technician in an academic lab before moving to Nashville, TN for graduate work at Vanderbilt University where he joined the Department of Pharmacology. Brain’s work there primarily focused on structure prediction of GPCRs from sparse experimental data. He then moved to the University of California in San Francisco to continue his training as a postdoctoral researcher where he used structural models of GPCRs to virtually screen large compound libraries with the goal of finding new chemical matter to probe understudied and orphan receptors. Brian is involved in organizing the GRC/GRS Molecular Pharmacology meeting, which has been postponed to 2023. Brian is one of the organizers of the upcoming Transatlantic ECI GPCR Symposium . Dr. Brian Bender on the web LinkedIn Twitter ResearchGate Dr.GPCR Member Google Scholar Dr. GPCR Ecosystem 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) Re-cap of Endocrine Metabolic GPCR 2024 with the Organizers About Dr. Aylin Hanyaloglu Dr. Aylin Hanyaloglu has been a Principal Investigator at Imperial College London since 2007. She received her BSc in Human Biology from King’s College London in 1997, and while her Ph.D. commenced at the MRC Human Reproductive Sciences Centre, Edinburgh, a move to Perth, Australia resulted in her Ph.D. in Molecular Endocrinology being awarded in 2002 with Distinction from the University of Western Australia. Dr. Hanyaloglu undertook her postdoctoral training at the University of California, San Francisco with Professor Mark von Zastrow where she identified novel core cellular machinery critical for G protein-coupled receptor trafficking and signaling. Her research focuses on understanding the fundamental cell biological mechanisms regulating GPCR activity, including spatial control of GPCR signaling and receptor crosstalk, and applying these mechanisms for distinct GPCRs in diverse physiological and pathophysiological systems, with particular focus on women's health, pregnancy, and nutrient sensing in the gut. Her work is currently funded by Biotechnology and Biological Sciences Research Council (BBSRC), Diabetes UK, Wellcome Trust, and the Medical Research Council. Dr. Aylin Hanyaloglu on the web LinkedIn Endocrine Metabolic GPCRs Researchgate Twitter Imperial College London Elsevier Loop Dr. GPCR About Dr. Caroline Gorvin "Dr. Caroline Gorvin is a Wellcome Trust & Royal Society Sir Henry Dale Fellow at the Institute of Metabolism and Systems Research, University of Birmingham. She obtained her PhD in 2012 from the University of Oxford, where her research focused on the cellular mechanisms by which mutations in a chloride-proton antiporter cause the renal disorder Dent’s disease. Caroline continued to undertake postdoctoral research in Oxford, investigating the signalling and trafficking of the G protein-coupled receptor (GPCR), calcium-sensing receptor, and its role in calcium homeostasis. Caroline moved to the University of Birmingham in 2018 to establish her research group investigating metabolic GPCRs. Her current research focuses on how metabolic GPCRs cross-talk and interact to regulate appetite and bone metabolism." Dr. Caroline Gorvin on the web University of Birmingham Endocrine Metabolic GPCRs Society of Endocrinology Google Scholar ResearchGate Loop Twitter Dr. GPCR About Dr. Alejandra Tomas "Dr. Alejandra Tomas is a molecular cell biologist and Senior Lecturer at the Department of Metabolism, Digestion and Reproduction, Imperial College London. She obtained a PhD in Biochemistry from University College London and spent several years in Switzerland working on the study of membrane trafficking processes in pancreatic beta cells before returning to the UK, first to her Department at UCL and then to lead a laboratory at Imperial following the receipt of an MRC New Investigator Award in 2015." Dr. Alejandra Tomas on the web Imperial College London Endocrine Metabolic GPCRs ResearchGate Google Scholar LinkedIn Twitter Dr. GPCR 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. Mark Connor About Dr. Mark Connor Undergraduate BSc with Honours in Pharmacology from University of Sydney (1987, snake neurotoxins), Ph.D. from Department of Pharmacology, University of Washington (1992, mentor Charley Chavkin , sigma receptors). Postdoc with Graeme Henderson (Bristol, opioids and Ca signaling) and Mac Christie (Sydney, opioids in neurons, novel spider toxins). Grant-funded independent research positions from 2001 at University of Sydney (opioids and sensory neurons), Vollum Institute Portland (visiting scientist with Ed McCleskey, sensory neuron properties); Pain Management Research Institute (more opioids, cannabinoids and T-type Ca channels) and Brain and Mind Research Institute (Sydney). 2009, appointed Professor of Pharmacology at Macquarie University. Focus on study of drugs and toxins on GPCR (opioid, cannabinoid receptor) and ion channel (K, Ca, TRP channel) function; mostly electrophysiology and fluorescence-based reporters, but can grind and bind. Currently pursuing molecular pharmacology of phytocannabinoids and novel synthetic cannabinoids, with a focus on efficacy and novel targets. Interested in orthosteric and allosteric interactions, and still looking for some bias ... anywhere ... these days human only. Dr. Mark Connor on the web Researchers Twitter 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 >>

Career coach Lauren Solano on the skills PhDs undersell, the careers they don't know exist, and the introspection exercise that maps functions to scientific training. << Back to podcast list Strategic Partner(s) Lauren Solano: Mapping Careers Beyond the Bench This episode steps outside the usual GPCR research conversation to examine the career architecture around it. Lauren Solano, CEO and co-founder of Propel Careers, has spent more than a decade coaching PhDs and postdocs and recruiting for biotech and life sciences companies — a vantage point that makes her uncommonly clear about the gap between how scientists describe themselves and how the market reads them. The discussion explores how to translate scientific training into career options that are often invisible to bench scientists, ranging from medical science liaison and clinical research roles to business development, scientific communications, venture capital, and consulting. Solano unpacks the specific transferable skills PhDs consistently undersell — collaboration, leadership, proactive ownership, communicating across technical audiences — and introduces concrete tools for self-assessment and exploration, including the "loved it, loathed it" exercise and a permission-granted approach to informational interviewing. For Solano, the stakes are personal: she didn't know the career she now has was even possible in 2008, which is precisely why she maps the option space for the scientists she coaches today. About the Guest Lauren Solano is CEO and co-founder of Propel Careers, a Boston-based firm that coaches scientists and recruits for biotech and life sciences companies. She trained as a scientist and spent her first decade in preclinical and early clinical drug discovery before pursuing an MBA in 2007 and co-founding Propel in 2009. Her practice centers on helping PhDs and postdocs translate technical training into career paths they often don't realize are open to them. Each year she delivers roughly a hundred talks at universities and research institutions on resumes, negotiation, informational interviewing, and the mechanics of biotech hiring. Scientific Themes of the Conversation The gap between scientific training and the career vocabulary scientists need Transferable skills in the PhD toolkit — and why they go unlisted Informational interviewing as a research method for career planning The limits and real signals of "company culture" in biotech COVID-era shifts in scientist hiring and career reflection Title-function mismatches in life sciences job descriptions Key Insights from the Conversation 1. The "loved it, loathed it" exercise as a career compass Over any given week, note which tasks you enjoyed and which you dreaded. Separate that list from what you're good at — the overlap reveals which career functions, not titles, are worth exploring next. 2. Function over title Job titles in biotech are often creative and inconsistent — a medical science liaison might be called a "clinical information specialist." Scientists navigating a career change are better served mapping careers by tasks and functions first, and treating titles as secondary metadata. 3. PhDs consistently undersell their transferable skills After thousands of conversations with scientists, Solano has found that collaboration, leadership, proactive ownership, and translating technical content across audiences are not universal traits. PhDs tend to have them in unusual concentration — and tend to leave them off their resumes because they assume everyone else has them too. 4. Informational interviews are already permitted Graduate students and postdocs often feel uneasy reaching out to people in other careers, as if the exploration hasn't been earned. Solano reframes this directly: because training ends, career exploration is required, and most people will give fifteen minutes if asked well. 5. "Company culture" is meaningless until you can point at behaviors Every company claims a strong culture. What matters is whether office layout, mentorship practices, and daily behaviors support the claim. The sharper question is what the company does , not what it says. 6. Safety at work is a concrete culture signal Would an employee feel comfortable telling a manager their child is sick, or would they invent another reason? Whether people feel safe at work is a harder measure of culture than any mission statement. 7. Post-pandemic career decisions are about alignment, not just advancement Solano observes that many scientists are using the moment to ask whether their current work matches who they are — not to chase the next rung, but to reset toward impact. Episode Timeline 00:00 Intro and Dr. GPCR Summit preview 01:30 Meet Lauren Solano and Propel Careers 03:11 The path from bench science to career coaching 07:56 Loved it, loathed it — the introspection exercise 10:29 Career options PhDs rarely consider 11:49 Transferable skills scientists undervalue 14:16 The informational interview — permission granted 23:57 The COVID shift in biotech hiring 26:14 Assessing real company culture 31:34 Master resumes and the title trap Timestamps were generated using AI for readability. Selected Quotes "If you had asked me in 2008 if I would be a recruiter slash career coach, I didn't even know that was possible because it hadn't even occurred to me that that is something that would have been a fit." "None of you should be ever worried or afraid or feel awkward reaching out to people for informational interviews because you are supposed to think about your future and learn about different things." "I can tell you in speaking with thousands of PhDs, not everyone is collaborative. Not everyone likes to do novel areas of research. Not everyone is amazing at communicating both to technical audiences and non-technical audiences. So don't undersell your experiences." "Life is frail, right? So if we're not making a difference, if we're not impacting something, why are we doing it?" About this episode In this special Dr. GPCR podcast episode, we sat down to chat with Lauren Celano to talk about career options for Ph.D.’s. Working in a lab allows scientists to gain amazing hard and soft skills, which opens the doors to several great careers that many have not even considered, yet. Lauren has a science background and is passionate about helping talented scientists find their dream position. She is also a speaker, connector, recruiter, and coach. Lauren Celano on the web LinkedIn Propel Careers Email: Lauren@propelcareers.com 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. Katarina Nemec About Dr. Katarina Nemec " I am a pharmacist with an interest in systems pharmacology and precision medicine. Since my undergraduate studies, I have been engaged in researching molecular mechanisms that govern human (patho-)physiology and their interplay with drugs. I aim to discover new therapeutic approaches, and druggable molecules or refine canonical drug targets to create drugs with fewer adverse effects. I studied Pharmacy at the University in Ljubljana, Slovenia, and at the University of Bonn, Germany, working initially on the role of prostaglandin receptor EP4 in chronic lymphocytic leukemia. During my PhD studies in Martin Lohse lab at the Max Delbrueck Center in Berlin, I consolidated my knowledge of GPCRs pharmacology while performing various cell-based experiments to understand the binding, activation, and signaling of therapeutically relevant GPCRs. In addition, I generated various optical biosensors based on fluorescence or bioluminescence resonance energy transfer technologies (FRET, BRET) that were used for functional screens with state-of-the-art microscopy and high throughput screening to explain novel ways of GPCR modulation. I am continuing with the development of advanced screening approaches in the Madan Babu lab to progress in the understanding of spatiotemporal regulation of biased GPCR activation and signaling. I want to combine experimental approaches with data-driven discovery and adopt data science methodology to tackle relevant scientific questions on the systems pharmacology level. " Dr. Katarina Nemec on the web Babu Lab ResearchGate Google Scholar ORCID LinkedIn Twitter 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 >>

<< Back to podcast list Strategic Partner(s) Dr. Yamina Berchiche About this episode In this Episode 0 of the brand new Dr. GPCR podcast , your host and founder, Dr. Yamina Berchiche introduces the very first podcast dedicated to GPCRs researcher and their work. This podcast is part of the Dr. GPCR Ecosystem, with the goal is to bring together GPCR scientists, biotech, and pharma leaders as well as suppliers working on GPCRs by providing opportunities to connect, share, form trusting partnerships, grow, and thrive together to accelerate GPCR drug discovery and improve human health. Dr. Yamina Berchiche on the web - Website - LinkedIn - PubMed - Twitter - Facebook - Dr. GPCR Ecosystem 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. Graciela Piñeyro on what happened when her lab tested biased agonism at the μ-opioid receptor across 25 ligands, why δ-opioid receptors recycle from the lysosome, and the quantitative pharmacology that turned an early artifact into a career of receptor work. << Back to podcast list Strategic Partner(s) Graciela Piñeyro: Partial Agonism, Receptor Recycling, and the Limits of Bias For over a decade, biased agonism at opioid receptors offered a clean route to analgesics without the respiratory depression and tolerance that have defined opioid therapy. If the right ligand could engage G-protein signaling while sparing β-arrestin, pain relief might finally be separable from side effects. In this conversation, Dr. Graciela Piñeyro — who leads an opioid receptor pharmacology group at the CHU Sainte-Justine Research Center and the Université de Montréal — walks through what happened when her lab tested that hypothesis rigorously. Across 25 ligands profiled at the μ-opioid receptor, the team found no bias, only partial agonism. Recent β-arrestin knockout work from Australia, Germany, and the UK has converged on a similar sobering conclusion. The conversation also traces her earlier work showing that δ-opioid receptors recycle from the lysosome — the compartment meant to degrade them — and how recycling patterns, not internalization itself, predict analgesic tolerance. For Dr. Piñeyro, a physician-turned-pharmacologist whose early project in Michel Bouvier's lab felt like "torture" until the right quantitative model turned her artifacts into real pharmacological responses, the throughline has never been building a career. It has been a refusal to treat messy data as noise until the right math arrived to make sense of it. About the Guest Dr. Graciela Piñeyro is a principal investigator at the CHU Sainte-Justine Research Center and a professor in the Department of Pharmacology and Physiology at the Université de Montréal. Trained as a physician in Uruguay, she began doing research in the only way then available to her — through a medical pharmacology department studying how benzodiazepines and alcohol affected sleep architecture. She completed her PhD at McGill University with Claude de Montigny, working on serotonin and antidepressant mechanisms, and her postdoctoral training with Michel Bouvier at the Université de Montréal, where she shifted into opioid receptors. Her lab now studies δ- and μ-opioid receptor signaling, biased agonism, receptor trafficking and recycling, and more recently the cannabinoid entourage hypothesis — combining BRET-based biosensors, quantitative pharmacology, and clustering approaches to connect in vitro signaling signatures to clinical side-effect profiles. Scientific Themes of the Conversation The limits of biased agonism at the μ-opioid receptor — and why partial agonism keeps explaining what bias was supposed to δ-opioid receptor recycling from the lysosome — and why the post-internalization fate of a receptor predicts tolerance better than internalization itself Protean agonism and multiple active conformations — how the same ligand can behave as agonist or inverse agonist depending on receptor tone Quantitative pharmacology as rescue operation — using operational models and BRET-based biosensors to pull pharmacological signal out of what first looks like experimental noise The defense of simple systems — why HEK-cell data can still predict FDA pharmacovigilance outcomes, and where iPSC-derived somatic systems actually pay their cost The cannabinoid entourage hypothesis as a pharmacological question — turning folkloric claims about complex mixtures into testable quantitative work Key Insights from the Conversation Twenty-five μ-opioid ligands produced partial agonism, not bias. When Dr. Piñeyro's lab systematically compared G-protein and β-arrestin recruitment across 25 compounds — standard opioids and new ligands from Pfizer — they could not identify a ligand-bias signature. What they could do was classify the compounds by relative efficacy, and that classification alone predicted clinical side effects. β-arrestin is not the villain it was made to be. Newer knockout work from groups in Australia, Germany, and the UK has shown that respiratory depression from opioids persists in β-arrestin-null mice. The mechanistic story that guided a decade of biased-ligand drug discovery needs rebuilding from the underlying biology, not from the pathway labels. The δ-opioid receptor recycles from the lysosome, and the recycling pattern determines tolerance. Long treated as a non-recycling receptor destined for degradation, the δ-opioid receptor can in fact return from the lysosomal compartment. In Dr. Piñeyro's framework, the ligands that permit recycling are the ones that produce less tolerance, whether acute or chronic — an inversion of the older view that internalization itself was the key variable. A quantitative model can turn an artifact into pharmacology. Early in her postdoc, Dr. Piñeyro watched the same ligand behave as an agonist under one condition and an inverse agonist under another. The resolution came not from a new experiment but from a model — protean agonism, as Kenakin had just described it, combined with André deLéan's software for estimating active receptor conformations — which revealed that the apparent contradiction was a quantitative signature of multiple active conformations. HEK cells still earn their keep. Even as the field pushes toward iPSC-derived somatic systems, HEK-cell signaling profiles of μ-opioid ligands correctly predicted outcomes logged in the FDA pharmacovigilance database. Dr. Piñeyro argues that the predictive power of the simpler system, and the real cost of the more elaborate one, should be weighed honestly before the field walks away from what works. The cannabinoid entourage hypothesis deserves a rigorous test. Instead of treating cannabinoids as single molecules, her group is asking whether complex mixtures of cannabinoids and terpenes produce analgesic responses that pure compounds cannot — and whether the mechanism involves allosterism across GPCRs, TRPs, and enzymes of the endocannabinoid system. The open question about THC's long-term effects on adolescent cognition sits alongside the analgesic one, and both require the same quantitative discipline. Follow the questions, not the career. Asked what advice she gives young scientists, Dr. Piñeyro's answer is blunt: she does not think of herself as having built a career. She followed interests that pulled her. In a funding environment that rewards the opposite, the advice is harder to take than it sounds — and, in her telling, the only thing that sustained her through the years when the data refused to make sense. Episode Timeline 00:00 — Introduction 01:57 — Meet Dr. Graciela Piñeyro 02:45 — From Uruguay to McGill: the cold email that changed a career 04:40 — The closed door that opened another: landing in Bouvier's lab 05:30 — The side project that became the real work 08:22 — Protean agonism and the model that rescued the data 11:00 — δ-opioid recycling from the lysosome and the question of tolerance 14:43 — 25 μ-opioid ligands, no bias, and the β-arrestin reversal 21:11 — Receptor tuning and the quantitative discipline behind the analysis 24:25 — The case for HEK cells in an age of iPSC enthusiasm 30:40 — Cannabinoids, the entourage hypothesis, and THC in teenage brains 43:20 — Follow the question, not the career Timestamps were generated using AI for readability. Selected Quotes "We tried to look for bias and classify our drugs, new and standard drugs, according to a bias signature — but there was no bias signature. What we could do was classify our drugs according to the relative efficacies. And from those relative efficacies, we were able to predict secondary effects in the clinic." "The only idea to be able to measure and predict something will transform your artifact into a real response. So that is why I got so into the models — in order to salvage my project." "We found that the receptor is sent to the lysosomes, as it has been said — but it recycles from the lysosomes." "I do not think I have a career. What I do have is — I was interested in questions and I followed my questions. I was not building a career. I was simply following my interests." About this episode Dr. Graciela Pineyro’s love for GPCR pharmacology started in Uruguay where she first worked on the serotonin receptors. This interest in research and pharmacology took Graciela to Canada where she stayed ever since she arrived for her Ph.D. work. Graciela has done extensive work on the molecular pharmacology of opioid receptors, exploring their signaling, trafficking, and their ability to activate different signaling pathways and signaling bias. Today, Graciela and her team’s efforts are directed towards the characterization of the pharmacological properties of cannabinoids in conjunction with terpenes for pain relief. Dr. Graciela Pineyro on the web Dr. Graciela Pineyro on LinkedIn Dr. Graciela Pineyro - University of Montreal Dr. Graciela Pineyro - CHU Ste-Justine Research Centre Pineyro Lab Publications on Google Scholar Pineyro Lab on 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) Dr. Nicolas Gilles About Dr. Nicolas Gilles "Dr. Nicolas Gilles is an expert in the study of animal toxins. He is pioneering the investigation of animal toxins acting on GPCRs, the largest therapeutic target class. His strongest expertise lies in therapeutic target identification and all the steps from venom manipulations, to in vivo validation. When the pharmacological properties of these new ligands are deemed exceptional, a lead optimization is realized and its therapeutic development initiates through a dedicated start-up." Dr. Nicolas Gilles on the web Google Scholar 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 >>

<< Back to podcast list Strategic Partner(s) Dr. Adriano Marchese About Dr. Adriano Marchese Adriano Marchese is a Professor of Biochemistry at the Medical College of Wisconsin. Adriano received his Bachelor of Science degree in Pharmacology in 1991 from the University of Toronto. He continued his graduate studies at the University of Toronto where he earned his MSc (1994) and Ph.D. (1998) in Pharmacology. He then moved to Thomas Jefferson University in Philadelphia, PA, for his postdoctoral training in Jeff Benovic’s laboratory studying the regulation of G protein-coupled receptor trafficking and signaling. In 2004 Adriano joined the faculty of the Department of Pharmacology at Loyola University Chicago. In 2016 he decided to move his lab to the Medical College of Wisconsin in Milwaukee, WI. Adriano’s research has contributed to our understanding of the role that ubiquitin plays in GPCR signaling and trafficking. His laboratory is interested in understanding the mechanisms that govern spatial and temporal regulation of GPCR signaling by -arrestins and post-translational modifications (PTMs), such as phosphorylation, ubiquitination, and SUMOylation. His lab has shown a role for -arrestins and PTMs in GPCR trafficking and signaling and has leveraged this knowledge to reveal the spatial and temporal requirements for GPCR activation of signaling pathways related to cell survival, proliferation, and migration. The ultimate goal of Adriano’s research is to target novel aspects of GPCR signaling for therapeutic development. Dr. Adriano Marchese on the web Twitter LinkedIn Google Scholar Website 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 >>