<< Back to podcast list Strategic Partner(s) Dr. G. Aditya Kumar About Dr. G. Aditya Kumar Dr. Aditya Kumar is a postdoctoral fellow at the University of Michigan Medical School. Aditya is interested in understanding the role of the membrane microenvironment in the subcellular organization, trafficking, and signaling of GPCRs. He received his Ph.D. from the Centre for Cellular and Molecular Biology at Hyderabad, India, where he studied the interaction of membrane cholesterol with the serotonin-1A receptor and its effects on receptor signaling and endocytosis. In addition, he explored the role of the host membrane in the entry of intracellular pathogens into macrophages. He currently uses high-resolution fluorescence microscopy and biochemistry to study GPCR trafficking mechanisms. In his (future) independent research career, Aditya aims to work at the interface of GPCR molecular pharmacology, subcellular trafficking, and membrane biology to better understand how the dynamic receptor microenvironment contributes to GPCR organization and function. Dr. G. Aditya Kumar on the web University of Michigan Puthenveedu Lab Google Scholar NIH 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 >>

A conversation with Dr. Tore Bengtsson on β₂-adrenergic receptor signaling, muscle metabolism, and how GPCR pharmacology can lead to new therapies for metabolic disease. << Back to podcast list Strategic Partner(s) Tore Bengtsson: Rethinking β₂-Adrenergic Signaling in Metabolic Disease Scientific Abstract This conversation with Dr. Tore Bengtsson , professor of physiology at Stockholm University, explores how β-adrenergic receptor signaling can be reimagined to address metabolic disease, muscle physiology, and energy balance. Dr. Bengtsson’s research spans sympathetic nervous system signaling, brown adipose tissue biology, and skeletal muscle metabolism—fields deeply connected to obesity, type 2 diabetes, and metabolic health. A central theme of the discussion is the pharmacology of the β₂-adrenergic receptor , a GPCR traditionally associated with bronchodilation but increasingly recognized for its broader physiological roles. Dr. Bengtsson describes how classical β₂ agonists stimulate muscle growth and metabolic changes but are limited by receptor desensitization. His work focuses on developing novel β₂-adrenergic ligands that selectively engage signaling pathways without triggering rapid desensitization, enabling sustained metabolic effects. The conversation also examines how GPCR signaling is far more complex than a single downstream pathway. Instead, receptors integrate multiple signaling outputs, temporal dynamics, and interactions with other pathways to shape physiological outcomes. Dr. Bengtsson discusses how understanding this signaling complexity opens opportunities to design drugs that promote beneficial metabolic responses such as muscle growth and increased energy expenditure. Listeners gain insight into how basic GPCR pharmacology can translate into therapeutic strategies targeting metabolism, aging, and metabolic disease. About the Guest Dr. Tore Bengtsson is a professor of physiology at Stockholm University whose research focuses on sympathetic nervous system signaling, metabolic regulation, and skeletal muscle physiology. His work investigates how β-adrenergic receptors regulate energy metabolism, muscle growth, and glucose homeostasis. Dr. Bengtsson began his research career studying brown adipose tissue under the mentorship of Dr. Barbara Cannon and Dr. Jan Nedergaard, pioneers in thermogenesis research. His laboratory now explores how β₂-adrenergic receptor signaling can be manipulated to influence metabolism and muscle physiology. He is also an entrepreneur and founder of biotechnology companies translating GPCR pharmacology into therapeutic development. Scientific Themes of the Conversation β-adrenergic receptor pharmacology and signaling bias Sympathetic nervous system control of metabolism Brown adipose tissue and thermogenesis Skeletal muscle metabolism and glucose homeostasis GPCR signaling complexity and pathway selectivity Translating receptor pharmacology into metabolic therapeutics Key Insights from the Conversation A Childhood Physiological Experiment Sparked a Scientific Career Dr. Bengtsson recounts a formative experience when his father pushed him into icy water as a child to demonstrate survival in cold conditions. The intense physiological response—an adrenaline surge and rapid adaptation to cold—sparked his lifelong fascination with sympathetic nervous system signaling and stress physiology. Stress Is Not Always Negative A recurring theme in the discussion is that physiological stress is often misunderstood. Short bursts of stress—whether exercise, cold exposure, or sympathetic activation—can trigger adaptive responses that improve metabolic function and resilience. Muscle Is Central to Metabolic Health While brown fat has received considerable attention, Dr. Bengtsson emphasizes the dominant role of skeletal muscle in metabolic regulation. Approximately 75% of glucose disposal occurs in muscle, making muscle physiology central to metabolic diseases such as type 2 diabetes. Classical β₂ Agonists Have a Fundamental Limitation Traditional β₂-adrenergic agonists can stimulate muscle growth and fat loss but lose effectiveness over time due to receptor desensitization. This pharmacological limitation prevents their long-term use for metabolic therapies. GPCRs Do Not Produce a Single Signal Dr. Bengtsson highlights that GPCR signaling is inherently multidimensional. Activation of a receptor can generate multiple signaling pathways, and different ligands can bias signaling toward specific outcomes. Understanding this complexity is essential for modern drug discovery. Absence of a Signal Can Be a Discovery One of Dr. Bengtsson’s key scientific breakthroughs came from an unexpected experimental result: glucose uptake without detectable cAMP signaling. Rather than dismissing the result as an error, this observation led to the realization that β₂ signaling could be separated into distinct pathways. Scientific Discovery Requires Intellectual Independence Dr. Bengtsson advises young scientists to shift from passively following instructions to actively questioning experiments and interpretations. True scientific thinking begins when researchers take intellectual ownership of the questions they pursue. Episode Timeline 00:00 Introduction and research focus of Dr. Bengtsson 03:00 A childhood experiment that sparked interest in physiology 07:00 Cold exposure, sympathetic signaling, and brown fat research 10:00 β₂-adrenergic receptors and muscle physiology 15:00 Exercise, metabolism, and pharmacological modulation of muscle growth 17:30 Early research on brown adipose tissue and thermogenesis 22:30 Translating academic discoveries into biotech companies 25:00 GPCR signaling complexity and biased signaling 36:00 A key experimental observation leading to a new drug concept 38:30 Advice for young scientists and intellectual independence Selected Quotes “You will not know what happens before you do the experiment.” “People think a receptor produces one signal. In reality, a receptor produces many signals.” “Sometimes the most important discovery is when a signal is missing.” “You have to move from being told what to do to thinking for yourself.” Full Transcript (Formatted for readability — full transcript preserved) Yamina Berchiche: Hello, everyone. This is Yamina from Dr. GPCR. And today I'm very excited to have with me Dr. Tore Bengtsson. Dr. Bengtsson: Tore Bengtsson. And you got it right. Yamina Berchiche: I'm happy to have you on. For those who don't know, we've been chasing each other and postponing this conversation several times. I'm very excited that we're finally able to do it today. Dr. Bengtsson: Thank you. I'm very happy to be here. Yamina Berchiche: Let's start at the beginning. Could you introduce yourself and tell us about your research? Dr. Bengtsson: I'm a professor in physiology at Stockholm University. I've been working with pre-diabetes, type 2 diabetes, obesity, and the mechanisms behind these diseases for about 25 years. I'm especially interested in β-adrenergic receptors because I believe they regulate far more physiological processes than people typically assume. I'm also an entrepreneur. I've started several companies. One is Sigrid Therapeutics, which focuses on digestion and metabolic regulation. Another company, Atrogi, is based on our research on β₂-adrenergic receptors and the development of new drugs. We’ve already completed Phase I clinical trials and are preparing for Phase II. Yamina Berchiche: If you were not a scientist, what would you be doing? Dr. Bengtsson: I think I might have been a historian or a writer. I like storytelling. I'm very interested in Viking runes and ancient rune stones in Scandinavia. I can actually read runic inscriptions, and I find it fascinating to interpret what these stones tell us about history. Yamina Berchiche: How did you become a scientist? Dr. Bengtsson: I'll tell you a story I don't share very often. When I was about ten years old, I lived on an island in the Stockholm archipelago. My father and I went ice skating frequently during the winter. One summer he asked me: “What happens if you fall through the ice?” I said I didn't know. He replied: “We should test it.” Months later, during winter, he cut a hole in the ice. I asked what he was doing. He said he was catching a big fish. Suddenly he pushed me into the icy water. I went under, looked up at the hole in the ice, and quickly swam out. I remember the intense adrenaline surge. My body reacted instantly. I wasn't even cold at first. Walking home later I started to freeze, but in that moment I experienced a powerful physiological response. That event sparked my lifelong fascination with sympathetic nervous system activation. Yamina Berchiche: So your father pushed you into science quite literally. Dr. Bengtsson: Yes — and into physiology. Yamina Berchiche: And that connects directly to your later work on brown fat and sympathetic signaling. Dr. Bengtsson: Exactly. I've spent many years studying brown adipose tissue and how sympathetic activation stimulates thermogenesis. Later I became increasingly interested in skeletal muscle metabolism and how β₂-adrenergic signaling affects muscle growth and glucose metabolism. Yamina Berchiche: Could you talk about how β₂-adrenergic signaling relates to muscle growth? Dr. Bengtsson: For many years it's been known that β₂ agonists can stimulate muscle growth and reduce fat. This has been observed in athletes and even in livestock production. But traditional β₂ agonists lose effectiveness over time because the receptor becomes desensitized. The body adapts, requiring higher doses. That makes them unsuitable as long-term therapeutic drugs. So about 15–20 years ago I began working on the idea that we need a new type of β₂ agonist—one that activates the receptor differently and avoids desensitization. That’s what we’ve now achieved with new compounds that stimulate the receptor in a novel way. Yamina Berchiche: You mentioned something very important earlier: GPCRs don’t produce a single signal. Dr. Bengtsson: Yes. Traditionally people thought receptor activation leads to one downstream pathway. But GPCRs activate multiple signaling pathways simultaneously. Different ligands can bias signaling toward different pathways. That means we can design compounds that favor beneficial physiological responses while avoiding unwanted effects. That is exactly what makes GPCR pharmacology so fascinating and powerful. Yamina Berchiche: You mentioned an important experimental moment that led to your drug concept. Dr. Bengtsson: Yes. A doctoral student ran an experiment measuring glucose uptake. The compound produced strong glucose uptake but almost no cAMP signaling. She thought the experiment had failed. But I realized this might be something important: glucose uptake without cAMP. And that turned out to be correct. That observation opened the door to separating signaling pathways and designing new β₂ ligands. Yamina Berchiche: What advice would you give to young scientists? Dr. Bengtsson: Young scientists often follow instructions without asking why. Real science begins when you take control of the question. You must move from being told what to do to thinking independently. You have to be in the driver's seat of your own thinking. Yamina Berchiche: That’s a powerful message. Dr. Bengtsson: And another lesson I learned from my wife: success often depends not just on knowledge but on understanding how other people think. Science is not just experiments. It's communication, persuasion, and collaboration. Yamina Berchiche: Dr. Bengtsson, thank you very much for the conversation. Dr. Bengtsson: Thank you. This was great. Yamina Berchiche: Bye. Dr. Bengtsson: Bye-bye. 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 >>

<< Back to podcast list Strategic Partner(s) Irfan Dhanidina, Dr. Kathleen Caron and Dr. Lauren Slosky About Irfan Dhanidina "My interest in oncology research led me to pursue a BSc in Biology & Economics from Carleton University, and an MSc in Biotechnology at McGill. However, after insightful experiences in academic, hospital, and industry labs, I decided to pursue a role in business development. In my role at Orion Biotechnology, I work at the intersection of science and business, which includes target selection, preclinical strategy and business development. With respect to GPCRs, I'm particularly interested in peptide/small protein receptors and the mechanisms that facilitate their role in various indications. To that end, I'm grateful to be working alongside the very talented team at Orion who translate important GPCR research into novel therapies for patients. " Irfan Dhanidina on the web LinkedIn The Org DIBIZ Dr. GPCR About Dr. Kathleen Caron " "Kathleen M. Caron, Ph.D. is the Frederik L. Eldridge Distinguished Professor and Chair of the Department of Cell Biology & Physiology at The University of North Carolina at Chapel Hill—a large, interdisciplinary basic science department consistently ranked in the Top 5 in the Nation in NIH funding. Dr. Caron received a BS in Biology and BA in Philosophy at Emory University and a PhD at Duke University while training with Dr. Keith Parker to elucidate the role of steroidogenesis in regulating sexual determination and adrenal and gonadal development using genetic mouse models. She pursued postdoctoral training with Nobel Laureate Dr. Oliver Smithies at UNC-CH, where she was the first to discover the essential role of adrenomedullin peptide for embryonic survival. With a special emphasis on G protein coupled receptors and receptor activity modifying proteins in vascular biology, the Caron laboratory has gained valuable insights into the genetic basis and pathophysiology of lymphatic vascular disease, preeclampsia and sex-dependent cardiovascular disease. Dr. Caron has received numerous awards including a Burroughs Wellcome Fund Career Award in the Biomedical Sciences, an Established Investigator Award and an Innovator Award from the American Heart Association, a Jefferson Pilot Award in Biomedical Sciences and a UNC-CH Mentoring Award. She currently serves as Associate Editor of Physiological Reviews; the #1 ranked journal in Physiology (IF 46.5). Dr. Caron is also past Associate Editor at JCI and served as the inaugural Associate Editor at ACS-Pharmacology and Translational Science. Dr. Caron currently holds multiple scientific advisory roles in academia, industry and the National Institutes of Health." " Dr. Kathleen Caron on the web UNC-Chapel Hill Department of Cell Biology and Physiology UNC Lineberger Comprehensive Cancer Center Twitter Google Scholar ORCID ResearchGate Dr. GPCR About Dr. Lauren Slosky "Lauren Slosky is an Assistant Professor in the Department of Pharmacology and a member of the Medical Discovery Team on Addiction, a multidisciplinary initiative within the University of Minnesota’s Medical School to advance research and treatment in the field of drug addiction. Dr. Slosky’s research is focused on understanding how neuropeptide G protein-coupled receptors (GPCRs) regulate motivated behavior and how these receptors can be targeted for therapeutic benefit. Dr. Slosky was awarded a B.S. with honors in Molecular and Cellular Biology and Psychology from The University of Arizona in 2011. She received a Ph.D. in Medical Pharmacology from The University of Arizona in 2015 and completed a postdoctoral fellowship in the laboratory of Dr. Marc G. Caron at Duke University. Dr. Slosky opened her laboratory at the University of Minnesota Medical School in 2021. While a postdoctoral fellow, Dr. Slosky characterized a new class of β-arrestin biased allosteric modulators (BAMs) for the neurotensin receptor 1. These ligands stimulate receptor β-arrestin recruitment without activating canonical G protein signaling. Critically, these ligands reduce addiction-associated behaviors in animal models without the side effects characteristic of balanced receptor activation. Because BAMs engage less well-conserved allosteric sites and exert pathway-specific effects on receptor signaling, they are exciting tools for linking distinct signaling pathways with their physiological effects and may serve as the basis for more selective therapeutics. This work was made possible by the optimization of longitudinal intravenous self-administration paradigms for genetically modified mice. Integrating GPCR biology, behavioral pharmacology, and systems neuroscience approaches, the Slosky Lab is now working to understand how the principles of receptor allosterism and functional selectivity can be leveraged in the development of safe and effective treatments for stimulant and opioid use disorders. Dr. Slosky’s work has been recognized through several travel and research awards, including the William James Psychology Award, the Hank Yamamura Endowed Fellowship in Pharmacology, an NIH F32 Postdoctoral Fellowship, and an NIH K99/R00 Pathway to Independence Award. In addition to research, Dr. Slosky is passionate about training the next generation of scientists and increasing diversity, equity, and inclusion in science. An advocate for trainees at all levels, she served as Service Chairperson and Interim President of the Duke University Postdoctoral Association. She is currently a faculty trainer for the University of Minnesota's MS and Ph.D. programs in Pharmacology, Graduate Program in Neuroscience, and Life Sciences Summer Undergraduate Research Program and is working to build relationships with key stakeholders through institutional and community service." Dr. Lauren Slosky on the web University of Minnesota Department Page Twitter LinkedIn Google Scholar PubMed Research Gate 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. Caron Tribute Part 1 About Marc Caron Dr. Caron and his family moved to Durham, NC in 1977, following receipt of his BSc in Chemistry from Laval University and his Ph.D. from the University of Miami. He joined the faculty of Laval University School of Medicine in 1975 and then returned to join Duke’s faculty, where he remained as a James B. Duke Professor until his death. He and his laboratory members studied the mechanisms of action and regulation of hormones and neurotransmitters and how they might underlie brain and behavior disorders such as schizophrenia, Parkinson's disease, attention-deficit hyperactivity disorder, mood disorders, and addiction. Among his many honors, Dr. Caron was an investigator of the Howard Hughes Medical Institute from 1992 to 2004, a member of the American Academy of Arts & Sciences, a fellow of the American Association for the Advancement of Science, and a recipient of the Julius Axelrod Award. An authoritative and prolific scientist, with over 650 scientific publications, he is most beloved as a mentor and his relentless encouragement that shaped the careers of hundreds of scientists worldwide. About our panelists in alphabetical order and the year they first met Dr. Caron Dr. Jeffrey Benovic (1985) Dr. Michel Bouvier (1985) Dr. Kathleen Caron - Co-host- (1970) Dr. Richard Cerione (1985) Dr. Brian Kolbilka (1987) Dr. Frederik Leeb-Lundberg (1984) Dr. Robert Lefkowitz (1973) Dr. Lee Limbird (1973) Dr. David Sibley (1988) Memories our panelists shared with us https://video.wixstatic.com/video/93ce84_92e3a06139244357b0823e3ecc294e27/1080p/mp4/file.mp4 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 >>

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Two Eurofins DiscoverX scientists on physiological relevance, the GPCRs that refuse to work, and why obesity biology brought the field back. << Back to podcast list Strategic Partner(s) Jane Lamerdin and Gaurav Agrawal: Building GPCR Assays That Reflect Real Biology GPCRs spent years in the background while pharmacology chased other targets. Obesity and GLP-1 biology changed that, and the largest target class is once again at the front of drug discovery. In this conversation, two Eurofins DiscoverX scientists reflect on what nearly three decades of building GPCR assays has taught them about what a trustworthy assay actually requires. The recurring theme is physiological relevance. Overexpressing a receptor produces a big, convenient signal, but it distorts the pharmacology and drifts away from what happens in a real cell. Lamerdin and Agrawal explain why the field, and increasingly regulators, now expect assays built closer to native expression, and why that raises the technical bar considerably. Along the way they discuss the receptors that simply refuse to yield an assay, from adhesion GPCRs to orphans trapped in the endoplasmic reticulum, and the long road from a discovery-grade assay to one robust enough for potency and lot release. For Agrawal it is personal: he spent his PhD on four GPCRs and now stewards 289, carrying those early lessons into every assay his team validates. About the Guests Jane Lamerdin is VP of R&D at Eurofins DiscoverX, where she oversees development of novel cell-based assays and tools for both portfolio expansion and client-focused projects. She brings more than twenty years of industry experience across diverse cell-based assays, supporting client drug discovery campaigns, method development, and qualification of assays for late-stage biologics. Her background spans high-throughput, molecular, and systems biology research, which lets her speak to what an assay needs at every stage of a program. Gaurav Agrawal earned his PhD in cell and molecular biology from the Indian Institute of Science, studying how GPCRs activate. During his postdoc at UC San Diego, he discovered a novel intracellular trafficking pathway essential for organelle biogenesis. At Eurofins DiscoverX, Agrawal leads market development for the cell-based assay portfolio and supports method transfers to CROs and CDMOs for biologics and biosimilars, keeping him in close contact with the scientists running these assays day to day. Scientific Themes of the Conversation Physiological relevance versus overexpression as the standard for a credible cell-based assay The company's arc from cyclic AMP screening into arrestin and internalization biology The obesity and GLP-1 resurgence that returned GPCRs to the front of drug discovery De-orphanizing GPCRs, including receptors stuck in the endoplasmic reticulum Moving a single GPCR assay from discovery through potency testing and lot release Community and client feedback as the real engine of new product development Key Insights from the Conversation Overexpression buys signal at the cost of truth. A single receptor can trigger a large, amplified cyclic AMP response, which makes overexpression assays convenient but unrepresentative. The easy readout drifts away from the biology researchers actually want to measure. Physiological relevance is now an expectation, not a preference. Regulators have begun telling companies directly that assays need to reflect near-primary expression levels. That raises the technical bar, since detecting such low expression pushes the limits of available methods. One assay is not one assay. A cell line that is excellent for discovery screening can be unsuitable for potency and lot release, where plate-to-plate, analyst-to-analyst, and year-to-year consistency become non-negotiable. Bridging that gap takes months of hardening work. Failure is documented, not buried. Decades of careful record-keeping on assays that never worked, from adhesion GPCRs to certain photoreceptor-like targets, let the team avoid reinventing dead ends and focus energy where progress is still possible. GPCRs never left; the attention did. For years the field's spotlight drifted to checkpoints and T-cell receptors. The obesity and type 2 diabetes wave brought GPCRs back to the front seat, and with it a fresh round of questions about how these receptors actually work. Scientists first, vendor second. The guests frame their work as talking to peers who understand the same pains, not selling a catalog. The support inbox and community collaborations feed directly back into what gets built next. Episode Timeline Timestamps were generated using AI for readability. 00:00 Meet the Eurofins DiscoverX scientists 03:20 From four receptors to 289: Agrawal's path into GPCRs 07:00 The Human Genome Project to pharmacology: Lamerdin's route 10:40 Why the largest target class still surprises them 21:40 How DiscoverX began, from cyclic AMP to arrestin 33:20 The assays that refused to work 36:30 De-orphanizing GPCRs stuck in the ER 46:40 Obesity, GLP-1, and the return of GPCRs 47:40 Physiological relevance as the real bottleneck 53:40 One message: scientists first Selected Quotes GPCRs are back. I'm very glad they're back in the front seat. Overexpression assays are not physiologically relevant. I like to call myself a jack of all trades, maybe master of none, but enough to be dangerous. You will not be disappointed to talk science about GPCRs when you reach out to us, and we love to talk to you. Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. 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. Graeme Milligan About Dr. Graeme Milligan Professor Graeme Milligan is Gardiner Professor of Biochemistry, Dean of Research, and Deputy Head of the College of Medical, Veterinary, and Life Sciences at the University of Glasgow. His main research group centers on the function, structure, and regulation of G protein-coupled receptors (GPCRs) and their interacting proteins. His experience also includes translating knowledge generated into the selection of targets, screening, and identification of small molecule regulators of these proteins, and progressing such ligands in drug development programs. Prof. Milligan has published more than 550 peer-reviewed articles and his research has been cited more than 35,000 times. He was elected to the Fellowship of the Royal Society of Edinburgh in 1998 and to the Fellowship of the Academy of Medical Sciences in 2016. Prof. Milligan is the co-founder of both Caldan Therapeutics (2015) which discovers novel therapeutics for metabolic diseases including Type 2 Diabetes and other indications including non-alcoholic steatohepatitis (NASH) and inflammatory diseases and Keltic Pharma Therapeutics (2020) which is developing new treatments for malaria. Dr. Graeme Milligan on the web University of Glasgow ResearchGate PubMed Orcid Google Scholar LinkedIn Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Jean Martin Beaulieu About Dr. Jean Martin Beaulieu Dr. Beaulieu received a Ph.D. in Neurological Sciences from McGill University and completed his post-doctoral training at Duke University. Prior to his recruitment Dr. Beaulieu was an associate professor and Canada Research Chair (Tier2) in the Department of Psychiatry and Neuroscience at Laval University. Dr. Beaulieu’s research is aimed at understanding how cellular and molecular mechanisms regulated by psychoactive drugs intersect with genetic risk factors for mental illnesses such as schizophrenia, depression, and bipolar disorder. Dr. Beaulieu has pioneered work establishing a role for Beta-arrestin signaling in the brain in vivo and has established its importance in D2 dopamine receptors (D2R) functions. These receptors belong to the super-family of G-protein coupled receptors (GPCR), the major molecular target for drug development. In particular, D2R is the main pharmacological target of antipsychotic drugs prescribed for schizophrenia and bipolar disorders. Work by the Beaulieu Lab has demonstrated that mood stabilizer drugs (e.g. lithium) used for bipolar disorder therapy target signaling mechanisms regulated by dopamine receptors, thus providing a framework to understand how different drug classes can engage overlapping cellular mechanisms to exert their action. The Beaulieu group is presently investigating how cell surface express proteins can act as allosteric modulators of D2R signaling and explores the potential usefulness of beta-arrestins for the development of new pharmaceutical agents. Translational validation is important to validate findings obtained from experimental models research and bridge the gap between bench and bedside. Working in collaboration with geneticists, the Beaulieu-Lab has identified interactions between cellular mechanisms engaged by D2R and psychiatric drugs with genetic risk factors implicated in schizophrenia by large whole-genome association studies (GWAS) in humans. These investigations have led to the identification of an RNA binding protein (FXR1P) involved in the regulation of protein synthesis as a potential downstream effector of the action of mood stabilizers and other psychoactive drugs. In addition to basic research, the Beaulieu group is also actively implicated in translational research and industry collaboration to develop new drugs and drug development technology. Dr. Jean Martin Beaulieu on the web University of Toronto Google Scholar LinkedIn ResearchGate Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Beatriz Blanco-Redondo on characterizing unknown adhesion GPCRs in Drosophila - receptor discovery, nocifensive behavior, and human disease links. << Back to podcast list Strategic Partner(s) Beatriz Blanco-Redondo: Adhesion GPCR Discovery in Drosophila Adhesion GPCRs are among the least characterized receptor families in the human genome , and in Drosophila Melanogaster, three of the five known adhesion GPCRs had no documented function, expression pattern, or signaling profile when Beatriz Blanco-Redondo's group began working on them. The receptors were named after condiments, ketchup, mayo, and remulate, not out of irreverence, but because no functional data yet existed to guide any other kind of nomenclature. Blanco-Redondo, group leader at the University of Leipzig, uses CRISPR engineering and in vivo behavioral assays to build the first systematic characterization of these receptors from the ground up. Her primary focus is Remulate, a neuronal adhesion GPCR with a human ortholog linked to vascular malformations and blood-brain barrier dysfunction in vertebrate models. The fly system makes it tractable: new lines in weeks, knockouts in months, and behavioral readouts that connect receptor loss to nocifensive phenotypes in larvae. For Blanco-Redondo, the pull toward this work is not abstract. Remulate is the receptor she secured funding to study, the one her first PhD student built an entire project around, and the one that still does not have a complete localization map. This conversation covers what it looks like to do receptor biology when you are writing the first chapter, without antibodies, no prior literature, and no established toolkit to fall back on. About the Guest Beatriz Blanco-Redondo is a group leader in the Department of Biochemistry at the University of Leipzig, where she studies adhesion GPCRs in Drosophila melanogaster. Her research focuses on characterizing the localization, signaling, and in vivo function of previously unknown adhesion receptors in the fly nervous system and gut. She trained in protein biochemistry and neuroscience, completing her PhD in Germany and her postdoctoral work at Columbia University, where she worked on ALS models using mouse systems. Since returning to Europe, her research has centered on receptor biology at the intersection of basic discovery and translational relevance. Scientific Themes of the Conversation First-contact receptor characterization, what it means to study a GPCR with no prior functional data Genetic tools for adhesion GPCR research in Drosophila, CRISPR, epitope tagging, and knockout strategies The logic of model organism selection : speed, genetic tractability, and translational value Nocifensive behavior as a readout for neuronal receptor function in larvae Human ortholog connections, from fly adhesion GPCRs to vertebrate vascular and neurological disease Career decisions in academic science, uncertainty, reentry, and the conditions that keep scientists in the lab Key Insights from the Conversation 1. Three adhesion GPCRs in Drosophila were functionally unknown until recently When Blanco-Redondo's group began this work, five adhesion GPCRs were known in the fly, but only two had any functional characterization. The other three had no documented expression pattern, signaling data, or phenotype. The approach was systematic: generate knockouts, introduce epitope tags, observe what breaks, and build the picture from scratch. There was no shortcut available because there was no prior literature to build on. 2. Naming receptors after condiments signals where the field actually stands Ketchup, Mayo, and Remulate were named in the absence of functional data that would normally guide nomenclature. It is a small detail, but it marks something real about the state of adhesion GPCR biology in insects: these receptors exist in a space where the biology precedes the vocabulary. The playfulness of the naming reflects the honesty of the situation. 3. Remulate connects fly neuroscience to human vascular and neurological pathology In the peripheral nervous system of Drosophila larvae, loss of Remulate disrupts nocifensive behavior - the animal's response to aversive stimuli. The human ortholog has been associated with vascular malformations and blood-brain barrier dysfunction in vertebrate models. That thread, from a behavioral assay in a fly larva to a clinical phenotype in mice, is what gives the model system its translational justification. 4. Antibody limitations drive the methodological design Because the antibody landscape for adhesion GPCRs is sparse and largely underdeveloped for fly receptors, Blanco-Redondo's group relies on CRISPR-introduced epitope tags to track receptor localization in vivo. This is not a workaround. It is a deliberate strategy that delivers spatial resolution that antibody-based approaches cannot offer for these targets at this stage of the field. 5. Drosophila generations close the experimental feedback loop A new fly line is ready in one to two weeks. A knockout can be generated and validated in two to three months. For receptor biology that requires iterative genetic manipulation - knocking out, tagging, rescuing, observing, this compression of experimental time changes which questions are tractable within a single grant period. It is not incidental to the science; it is part of the scientific logic. 6. Reconsidering a career is not the same as leaving science Blanco-Redondo describes a period after returning from New York when she was genuinely uncertain about continuing in the lab. The decision to stay came from a specific opportunity, a specific mentor, and a specific set of questions she hadn't yet answered. It did not resolve into a clean narrative. It was uncertain, and she says so plainly. 7. Negative results need infrastructure, not just tolerance Blanco-Redondo and Berchiche discuss the cost of unpublished negative data, particularly for PhD students working within three-year funding windows. The argument is not sentimental. If a failed approach were citable, it would shorten the path for the next researcher attempting the same thing. Some journals are beginning to accept negative data, and both agree this matters structurally. Episode Timeline Timestamps are AI-generated from the transcript and may not reflect the final edited episode precisely. Verify against the published video before use. 00:00 - Sponsor intro: GeneTex and Eurofins DiscoverX 00:29 - Introduction of Beatriz Blanco-Redondo; icebreaker 01:15 - Career path: from Spain to Germany, and the decision to go further 05:57 - Dr. GPCR University mid-roll 06:17 - Life in New York; comparing research cultures across continents 08:30 - How adhesion GPCRs entered the picture, and the shift toward receptor biology 11:49 - Research program in Leipzig: three unknown adhesion GPCRs in Drosophila 13:57 - Naming Remulate, ketchup, and mayo; why Remulate became the primary focus 15:47 - Lab methods: CRISPR, epitope tagging, colony generation timelines 17:29 - Behavioral and phenotypic readouts; nocifensive responses in larvae 18:48 - The human ortholog of Remulate and connections to vascular and neurological disease 22:58 - What first-contact receptor characterization actually looks like 26:02 - Career turning points; uncertainty on returning from the US 33:25 - Advice for scientists working on adhesion GPCRs and difficult model systems 35:26 - The case for publishing negative results; pressure on PhD timelines 40:54 - Upcoming GPCR conferences in Leipzig and Dusseldorf Selected Quotes "It's like there's nothing known at all about this receptor. And then you come into play and piece by piece you try to put the pieces together - it's like a puzzle. And then at the end, you can discover what a receptor that was there in the fly - nobody ever checked what it's doing." "When I moved back from the US, I was not sure I wanted to continue in science. Thanks to Toby, that gave me a position here, and I could stay. Yeah, I'm still here - so it means that I enjoy it." "You come from disease and then you're working on a receptor and you want to study what happens there. But then to see all the possibilities that this offers - that was also great." "Don't give up, because it's your passion, it's your job. We love what we do. And we have a lot of friends who don't like what they are doing. And this is very important." 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. Alex Serafini shares why pain research must start with real-world behavior and models before drilling into GPCR targets — a top-down rethink for drug discovery. << Back to podcast list Strategic Partner(s) GPCRs and the Science Behind Pain and Recovery with Dr. Alex Serafini Strategy: From Personal Pain to Scientific Purpose Dr. Alex Serafini’s entry into science wasn’t typical. Born in California, raised in Silicon Valley, and initially eyeing finance, his trajectory took a sharp turn after struggling with unresolved, chronic pain following repeated surgeries for a pilonidal cyst. "I wasn't able to get stronger pain meds because of the opioid epidemic," he recalls. That gap in care sparked a curiosity that became a career. Driven by personal experience and a desire to innovate in pain management, Alex pursued a master's in pain research at Hopkins and later an MD-PhD at Mount Sinai. His early exposure to TRPV1 channels and peripheral pain mechanisms with Dr. Mike Caterina laid the foundation. But the deeper mission? Finding answers for patients society often overlooks. Pain became more than biology — it became a personal strategy. “I started going through what I was going through… and that got me very interested in research.” — Alex Serafini Decision-Making: Saying Yes to the Unorthodox Path Serafini’s journey defied traditional checklists. He joined Mount Sinai through FlexMed — bypassing the MCAT — and was torn between a career in pharma and academia. At one point, he had a job offer at Roivant (a biotech firm known for repurposing shelved compounds), but a late-stage offer into an MD-PhD program — and parental “encouragement” — rerouted his path. His approach to decision-making is pragmatic: follow impact, not orthodoxy. The decision to stay on as a postdoc in the same lab as his PhD — with Dr. Venetia Zachariou — wasn't the typical next step, but it allowed him to wrap up high-impact work and learn about PI-level grant writing, strategy, and lab management. In his words: “She let me run projects like a junior PI.” “I didn’t need to chase new techniques — I needed to finish the science that mattered.” — Alex Serafini Blind Spots: The Underestimated Role of RGS Proteins in Pain Although not a self-proclaimed GPCR specialist, Serafini found himself repeatedly drawn to them, or more precisely, to RGS (Regulators of G protein Signaling) proteins. The lab’s work with RGS4 led to unexpected results: knockout mice spontaneously recovered from chronic pain after three weeks, an effect rarely observed. He points out that GPCRs—especially orphan and CNS-associated ones—are often downplayed in pain research, with most focus on ionotropic targets like NAV1.8. But Serafini believes that’s a blind spot. “We’re using outdated drugs. There are more elegant GPCR targets waiting to be explored.” The lab’s unconventional in vivo-first strategies, combined with RNA-seq and behavioral analysis, revealed nuanced roles of RGS4, RGS9, and RGSZ — not just as modulators but as potential therapeutic linchpins. “Half the time, in pain, what works in vivo doesn’t translate to clinic. We need new thinking.” — Alex Serafini Failure & Frustration: From Pipettes to Pandemic Disruption The road hasn’t been smooth. From struggling to grip mice in early animal studies to thesis delays during COVID-19, Serafini's journey is marked by grit. But it’s in these friction points that new insights emerged. The pandemic disruption, for instance, led him to BSL-3 labs to study persistent pain after SARS-CoV-2 infection, revealing novel immune-neuron signaling in DRGs. He also opens up about the emotional and logistical toll of MD-PhD training. It’s an eight-year-plus haul with built-in uncertainty. However, with mentors who believed in him, especially those who shared administrative, grant-writing, and leadership skills early on, he found direction and resilience. “She [Vanna] gave me a crash course in what it’s like to be a junior PI. That changed everything.” — Alex Serafini Pivoting: Redefining the Pain Research Playbook Looking ahead, Serafini’s vision is bold: build a lab that develops translational models of pain rooted in patient realities. He’s fascinated by transgenerational epigenetics — how parental pain, diet, or drug exposure can leave molecular fingerprints in offspring. He's equally focused on sex differences in pain processing and the failure of "one-size-fits-all" models in pharmacology. His advice? Learn broadly. Stay close to patients. Collaborate relentlessly. And above all, don’t be afraid to start from the phenotype and work backwards to the mechanism. That top-down approach, though less common, could help pain research finally catch up with the complexity of real-world biology. “Start from the end — from the clinic — and then build backwards.” — Alex Serafini Key Takeaway Innovation in pain research won’t come from doing the same things better — it’ll come from flipping the script. Whether it’s challenging legacy targets, redefining preclinical models, or exploring the epigenetic inheritance of pain, Dr. Serafini urges the field to stay bold, patient-centered, and GPCR-aware. About Alex Serafini Alex was born and raised in the Bay Area and received his BS/MS Neuroscience from Johns Hopkins. His master's degree was in Dr. Michael Caterina's lab studying the role of PNS chloride transporters in neuropathic pain. Upon matriculating to Mount Sinai's MD/PhD program, he joined Dr. Venetia Zachariou's lab to study the effects of chronic pain and addiction/withdrawal on the mesocorticolimbic system, focusing on transcription factor and RGS protein maladaptations, behavioral RGS protein drug "screening", and the role of SARS-CoV-2 on CNS function and sensory hypersensitivity. He aspires to become a physician-scientist, with a focus on translational in vitro and in vivo model development for studying chronic pain and affective comorbidities. Other academic interests of his include studying pharmaceutical finance & healthcare administration and developing technologies that increase healthcare access. His non-academic interests include traveling, scouting out micro-breweries, and collecting beer cans. Alex Serafini on the web LinkedIn 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. Fiona Marshall on structure-based GPCR drug discovery, the GABA-B heterodimer, the acetate that rewrote a receptor family, and why the same names keep filling GPCR conference agendas. << Back to podcast list Strategic Partner(s) Fiona Marshall: Three Decades Inside GPCR Drug Discovery This conversation traces how structure-based GPCR drug discovery moved from a stubborn crystallography problem to a generative platform — through the career of a scientist who helped engineer that shift. Dr. Fiona Marshall walks through the decade when membrane proteins kept failing to crystallize in detergent, and how Chris Tate's thermostabilization strategy finally made GPCR structures routine, the insight that seeded Heptares Therapeutics. The conversation moves across discoveries that shaped a generation of GPCR pharmacology: the GABA-B heterodimer, the free fatty acid receptors, the unexpected allosteric pockets that emerged once structures became available. It also confronts where the field still struggles — translating biased agonism from cell line to clinic, drugging orphan receptors without obvious phenotypes, and expanding the voices that define the field's agenda. For Dr. Marshall, the throughline is personal: she remembers the exact lecture at Bath where she first heard about the β-adrenergic receptor, and has spent three decades inside the rooms where GPCR drug discovery actually changed. About the Guest Dr. Fiona Marshall is VP and Head of Neuroscience Discovery at MSD, leading teams in West Point, Boston, and London. She co-founded Heptares Therapeutics and served as Chief Scientific Officer for twelve years, through the company's acquisition by Sosei, helping establish structure-based drug design as a productive strategy across GPCR families. Earlier, at GSK, she contributed to the identification of RAMP proteins, the GABA-B heterodimer, and ligands for orphan receptors including what are now known as FFA2 and FFA3. Her work spans GPCR structural biology, membrane protein stabilization, allosteric modulation, and the pharmacology of receptor families implicated in neuroscience, immunology, and metabolism. Scientific Themes of the Conversation Structure-based GPCR drug design and the thermostabilization breakthrough GPCR heterodimerization and the logic of accessory proteins (RAMPs, GABA-B1/B2) Allosteric modulation and non-orthosteric binding sites on GPCRs Biased agonism, target validation, and animal-to-human translation failure Orphan GPCRs and the missing pharmacology of ~100 unassigned receptors GPCRs in oncology, immunology, and microbiome-host signaling Key Insights from the Conversation Why Membrane Proteins Wouldn't Crystallize The bottleneck wasn't expression level, as most groups had assumed — it was the instability of the receptor in detergent. Chris Tate's thermostabilization strategy, which introduced stabilizing mutations selected by thermal assay, reframed the problem and opened the door to routine GPCR crystallography. Dr. Marshall is clear that the conceptual reframing, not a brute-force technical push, is what unlocked the field. The GABA-B Heterodimer Was Hiding in Plain Sight Dr. Marshall's team at GSK cloned GABA-B1, tried to get it to signal, and couldn't. A screen run to find an intracellular scaffolding partner pulled up something unexpected: a second GABA-B receptor. The moment baclofen activated ion channels in Xenopus oocytes expressing both — with Dr. Marshall in the room — a new category of GPCR biology opened, with heterodimers as obligate signaling units. The Ligand That Wasn't the Ligand Screening orphan receptors in yeast, the team chased peptide hits that made no SAR sense. The realization — triggered by Andrew Brown sitting with a table of actives and inactives — was that the active condition was the acetate buffer, not the peptide. The orphan was a free fatty acid receptor. Years of assumed peptide biology dissolved into a simpler truth hidden in the solvent. Structures Reveal Pockets the Field Didn't Know Existed Once GPCR structures became routine, unexpected binding sites emerged: extra-helical pockets on the glucagon receptor, intracellular sites for C5a antagonists, allosteric modulators bound far outside canonical regions. These discoveries rewrote what counts as "druggable" on receptors once considered fully mapped. Biased Agonism Needs Human Biology, Not Just Pathway Dials The promise of biased ligands — pulling one signaling arm while sparing another — only survives translation if the coupling profile in the relevant human cells matches the cell-line model. Dr. Marshall's caution is hard-won: many animal-model-validated GPCR drugs have failed in the clinic precisely because this step was skipped. Oncology Ignored GPCRs for Decades — and Is Paying Attention Now Twenty years ago, cancer biologists dismissed GPCRs: they weren't oncogenic and didn't kill tumor cells directly. The shift came through the tumor microenvironment — immune cells, chemokine receptors, adenosine signaling — where GPCRs now sit at the center of immuno-oncology strategies that tumor-intrinsic target lists missed. Thirty Years, and the Same Names Keep the Mic One of Dr. Marshall's most pointed observations: the people speaking at GPCR conferences today are, in large part, the people who were speaking at them twenty-five years ago. She frames this as a scientific problem — a narrowing of perspectives on hard problems — not only a social one, and argues the old guard should actively make room for the next cohort. Episode Timeline Timestamps were generated using AI for readability. 00:00 Welcome and guest introduction 02:32 How an undergraduate lecture on β-adrenergic signaling set a career in motion 07:07 A venture capital visit to the LMB and the founding of Heptares 11:28 Building a membrane protein team from scratch 15:29 Unexpected allosteric pockets and the next wave of GPCR drug design 18:47 Which GPCR families pharma is chasing now — and why 21:23 Why animal model validation keeps breaking in clinical trials 27:33 How oncology finally stopped ignoring GPCRs 36:39 The GABA-B heterodimer — the moment baclofen finally worked 40:06 The acetate-in-the-buffer discovery 41:47 Thirty years in, and the same speakers keep getting the mic Selected Quotes "We did the classic experiment in Xenopus oocytes, where you inject the cDNA of both the receptors together. And I was in the room when we then added on baclofen, the agonist, and we could see the ion channel activation." "He just sat down with a table of what was active or inactive. And then he realized the peptides that had been dissolved in acetic acid or acetate were the ones that were active... So it turned out that the ligands were not the peptides at all." "Having worked in GPCRs for 30 years and I look at the conferences, the same people are speaking now as was speaking 25 years ago. So can we now try and encourage the next cohort of people to be the main speakers at conferences?" "We had this really cool room where you could see — you put on 3D glasses and see the receptor in three dimensions sort of floating in the room and moving around." About this episode Fiona Marshall got fascinated with GPCRs after attending a lecture on how the beta-adrenergic receptor in the heart is activated by adrenaline, during her undergraduate studies at Bath University. She then pursued her Ph.D. in neuroscience at Cambridge University. An expert in GPCR biology, Fiona published the first description of the cloning and structural requirements of the GABAB receptor. One of her career path-defining moments came when she visited Dr. Chris Tate and Dr. Richard Henderson at the Laboratory of Molecular Biology in Cambridge, UK. As a co-founder of Heptares Therapeutics , now called Sosei Heptares , a GPCR-focused drug discovery and development biotechnology company, Fiona and her team made considerable breakthroughs in the field of GPCR stabilization and structure-based drug design. Today, Dr. Marshall is the VP Head of Neuroscience Discovery and Head of Discovery UK, Global Head of Neuroscience discovery research leading teams in West Point, Boston, and London at MSD. Join me and learn more about her fascinating career trajectory. Dr. Fiona Marshall on the web LinkedIn Twitter Google Scholar MSD UK Dr. GPCR Ecosystem 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 >>

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<< Back to podcast list Strategic Partner(s) Dr. Matthew Eddy About Dr. Matthew Eddy Matthew Eddy earned his BA in Chemistry from Oberlin College, where he trained with solid-state NMR expert Professor Manish Mehta . He then earned his Ph.D. in physical chemistry from the Massachusetts Institute of Technology, training under the mentorship of Prof. Robert Griffin . Following this, Dr. Eddy began learning and investigating human GPCRs while training in the laboratories of Professors Raymond Stevens and Kurt Wüthrich at The Scripps Research Institute. Dr. Matthew Eddy on the web 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 >>

Explore how GPCR signaling shapes mosquito feeding and mating behaviors with Dr. Laura Duvall. Insights for GPCR researchers and functional assay innovators. << Back to podcast list Strategic Partner(s) Why Mosquitoes Hunt You: GPCR Control of Blood Feeding and Mating This episode features Dr. Laura Duvall, whose research tracks the molecular mechanisms that govern mosquito behavior, focusing on the intersection of neuropeptide signaling and GPCR function. Dr. Duvall discusses her lab’s work dissecting how GPCRs—especially neuropeptide Y (NPY) receptors—regulate innate behaviors such as blood feeding and mating in Aedes aegypti . She shares approaches that combine genetic manipulation (CRISPR-Cas9) and functional behavioral assays, including high-throughput and video-based methods, to reveal these receptors’ roles. The conversation explores translational implications, such as leveraging conserved GPCR pathways to inhibit pathogen transmission, highlighting unexpected links between mosquito and human gut-brain signaling. Dr. Duvall emphasizes the value of model systems and cross-species discoveries in GPCR biology. Listeners interested in GPCR drug discovery, functional assay development, or fluorescence-based assays in behavioral research are encouraged to explore more episodes of the Dr. GPCR Podcast and consider the expanded content on Dr. GPCR University . Why This Matters? How GPCR-mediated neuropeptide signaling dictates mosquito attraction to humans, directly impacting disease transmission. Why the study of conserved receptor pathways enables the development of broadly effective, species-independent vector control strategies. What functional and behavioral assays in mosquitoes reveal about the underlying diversity of GPCR signaling across taxa. How dissecting receptor function in non-neuronal tissues uncovers new parallels to human gut-brain communication. Who Should Listen? This episode is essential for anyone advancing GPCR-targeted research in physiological or behavioral contexts. If you often translate receptor mechanism findings from model organisms to human systems. If you want to expand high-throughput or fluorescence-based assay strategies to non-traditional models. If you are interested in how behavioral outcomes emerge from cell-type-specific GPCR expression and signaling dynamics. If you are considering novel ways to connect molecular pharmacology with organismal phenotype, especially in vector biology or neurobiology. About Laura Duvall Laura Duvall trained in biochemistry and behavioral biology at the University of Pennsylvania. During her PhD with Paul Taghert at Washington University in St. Louis, she investigated neuropeptide control of circadian behaviors in Drosophila , with a specific focus on how GPCR family members orchestrate brain clock cell function. As a postdoctoral researcher in Leslie Vosshall’s laboratory at Rockefeller University, Dr. Duvall pivoted to the Aedes aegypti mosquito, focusing on the molecular regulation of feeding and reproductive behaviors via neuropeptidergic GPCR signaling. In 2019, Dr. Duvall established her laboratory at Columbia University, where she is part of the Department of Biological Sciences and the Zuckerman Institute. Recognized with the Beckman Young Investigator Award, the Klingenstein-Simons Fellowship in Neuroscience, and a Pew Scholarship, she continues to drive efforts to decode how evolutionarily conserved GPCR pathways modulate complex behavioral outcomes. Her research is consistently motivated by uncovering new biological connections that can bridge basic and translational science. Guest on The Web LinkedI n Google Scholar Lab 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. Sai Prasad Pydi About Dr. Sai Prasad Pydi Dr. Sai Prasad Pydi obtained his Ph.D. from the University of Manitoba – Canada, where he was introduced to G protein-coupled receptors (GPCRs) by Prof. Prashen Chelikani . His doctoral research focused on the structural and functional characterization of bitter taste receptors (T2Rs). In 2014, Dr. Pydi joined Dr. Jurgen Wess’s lab at the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) - NIH, USA as a postdoctoral fellow and trained on understanding the physiological role of GPCR signaling and beta-arrestins in diabetes and obesity. In February 2021, Dr. Pydi joined BSBE department at IIT-Kanpur. The main target of Dr. Pydi's laboratory is to develop GPCR-based drugs for the treatment of obesity and Type 2 Diabetes (T2D) by exploring metabolically important signaling pathways in immune cells and insulin-sensitive tissues (liver, pancreas, skeletal muscle, adipose tissue, and brain). His laboratory uses knock-out and transgenic mouse models, along with different cell culture systems, to understand the role of immune cell GPCRs and their cross-talk with other insulin-sensitive tissues regulating glucose and lipid metabolism. Dr. Sai Prasad Pydi on the web Molecular Metabolism & Cell Signaling Laboratory Website Twitter.com Research Gate PubMed Google Scholar Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

< Back The spatiotemporal organization of GPCR signalling September 10, 2026 10 AM - 11:30 AM EST 🔒 Watch Recordings - Join Premium Access the full library of recorded Masterclass sessions. Get Live Updates Be notified when new live Masterclasses are scheduled. Introduction GPCR signaling is organized in space and time. Where a receptor signals, how long it remains engaged, and which membrane it occupies all shape the downstream response, yet these events are averaged away by conventional population assays. This Masterclass examines the spatiotemporal organization of GPCR signaling and the optical methods that resolve it in living cells, down to individual molecules. Coverage spans the mechanisms of receptor signaling and trafficking, labeling strategies and quantitative imaging by FRET, BRET, and single-molecule microscopy, and signaling on internal membranes including endosomes and the Golgi. Intended for GPCR scientists, cell biologists, and drug discovery professionals working on receptor signaling dynamics, trafficking, and quantitative microscopy. Instructor Bio Davide Calebiro's work has reshaped how the field understands where and when GPCRs signal. Using single-molecule microscopy, FRET, and BRET to observe signaling directly in living cells, one molecule at a time, his team resolves how receptors and transducers interact in space and time, and how GPCRs signal from internal membranes such as endosomes and the Golgi, work with direct bearing on therapeutic directions such as biased agonists for metabolic disease. He is Chair of Molecular Endocrinology and a Wellcome Trust Senior Research Fellow at the University of Birmingham, where he heads the Department of Metabolism and Systems Science and co-directs the Centre of Membrane Proteins and Receptors (COMPARE). His Masterclass brings this single-molecule, imaging-driven view of receptor signaling directly to Dr. GPCR University. Upcoming Live Sessions

Dr. Jennifer Pluznick explains why olfactory receptors in the kidney are more than curiosities — they sense gut-microbe metabolites, modulate blood pressure, and are forcing a rethink of what "smell" actually means. << Back to podcast list Strategic Partner(s) Jennifer Pluznick: Olfactory Receptors in the Kidney and the Gut-Microbe Signal Olfactory receptors are known by a single address — the nose. But a microarray Dr. Jennifer Pluznick ran as a postdoctoral fellow placed them, surprisingly, at the top of a kidney gene expression list. She almost dismissed the result as an artifact. Instead, she followed it, and the decision has shaped the direction of her lab at Johns Hopkins ever since. In this conversation, Dr. Pluznick explores what changes when olfactory receptors are treated not as smell receptors but as general-purpose chemosensors — scattered across the body and tuned to ligands circulating in the blood. She walks through the kidney ORs her group has connected to renin release, to proximal tubule glucose handling, and to blood pressure regulation. One of those receptors is activated by small-molecule metabolites produced by gut microbes, a finding she still calls mind-blowing and that she continues to unpack. The conversation also surfaces the field's quiet bottlenecks: the trafficking problem that traps ORs in the ER, the orthology gap between 1,000 mouse receptors and 350 human ones, and the reagents — antibodies, agonists, antagonists — that the community still does not have. About the Guest Dr. Jennifer Pluznick is Associate Professor of Physiology at Johns Hopkins University School of Medicine. Her lab studies the role of understudied GPCRs — olfactory receptors, taste receptors, and orphan GPRs — in kidney physiology. Her group has linked specific kidney olfactory receptors to blood pressure regulation via the renin-angiotensin pathway, to glucose handling in the proximal tubule, and to circulating metabolites generated by the gut microbiota. She first encountered olfactory receptors in the kidney during her postdoctoral training, and her lab continues to deorphanize and functionally characterize them today. Scientific Themes of the Conversation Olfactory receptors as general-purpose chemosensors outside the nose Deorphanization strategies for kidney-expressed GPCRs The renin-angiotensin axis and OR-mediated blood pressure control Gut microbiota metabolites as endogenous GPCR ligands Receptor trafficking and the ER-retention problem for ectopically expressed ORs Mouse-to-human orthology in a highly expanded receptor family Key Insights from the Conversation A surprise at the top of a microarray. When Dr. Pluznick's postdoc screen flagged olfactory receptors as top hits in a kidney disease cell line, her first instinct was to distrust the data. A single comment from her advisor — olfactory receptors in the kidney could actually be really cool — reframed a possible artifact as a research program. Reframing olfactory receptors as chemosensors. The name "olfactory receptor" narrows the imagination. Dr. Pluznick argues they are better understood as chemical sensors that happen to dominate the nose. Once reframed that way, ectopic expression in tissues like the kidney stops seeming strange and starts making sense. Two kidney ORs with physiology attached. One OR her lab has studied modulates renin release and therefore blood pressure; another regulates glucose handling through a transporter family that includes a validated type 2 diabetes target. Both started as receptors with no known ligand, no known localization, and no reason to expect physiological relevance. Gut microbes at the other end of the signal. The OR linked to blood pressure is activated by small-molecule metabolites produced by gut bacteria at low millimolar circulating concentrations. That makes blood pressure regulation, in part, a readout of microbial metabolism — a connection Dr. Pluznick describes as something that still blows her mind. Trafficking as a field-wide bottleneck. Exogenously expressed ORs tend to get stuck in the ER. Matsunami's RTP1S chaperone, the Rho tag, and the Pluznick lab's Lucy tag — a cleavable leucine-rich signal sequence developed by a rotation student — each help, but no combination fully solves the problem for every OR. The trafficking failure itself may encode something about how tightly ORs are regulated in olfactory sensory neurons. The orthology gap. Mice have ~1,000 olfactory receptors; humans have ~350. Sequence-based orthology calls are often ambiguous, and in the Pluznick lab's hands, putative orthologs frequently fail to share ligand profiles. Finding functional orthologs — not just sequence matches — is non-trivial, and it matters for anyone hoping to translate kidney OR biology into a human drug. Follow the data that surprises you. Dr. Pluznick's advice to early-career scientists is shaped by her own near-dismissal of an inconvenient microarray result. Established assumptions about where a receptor "belongs" are often what stop a discovery from being recognized as one. Episode Timeline Timestamps were generated using AI for readability. 00:00 Opening: newsletter, season close, and welcome 02:13 Becoming a scientist as a first-gen college student 04:17 The case for chasing understudied GPCRs in the kidney 06:18 "Olfactory receptors will always be my first love" 08:45 Renin, blood pressure, and a glucose-handling receptor 12:14 Localization and ligand screening when there's no antibody 17:06 What happens to OR expression in a disease kidney 19:56 The orthology problem: 1,000 mouse ORs, 350 human ones 23:08 RTP1S, the Rho tag, and the Lucy tag 29:20 One-neuron-one-receptor and the tight regulation of smell 36:57 The aha moment: gut microbes, a GPCR, and blood pressure 39:58 Diversity as everyone's responsibility Selected Quotes "I famously said that I wasn't sure I could really trust the data because these crazy receptors came out as the top hits. But my postdoc advisor, who's much wiser than I, said, 'olfactory receptors in the kidney, though — that could be really cool.' And somehow when he said it, it sounded like a much better idea." "Olfactory receptors as a class will always be my first love in terms of GPCRs." "Your blood pressure regulation is somehow tied to the activity of your gut microbes. And that is something that still kind of blows my mind." "You need to follow your data, even when it surprises you, even when it might go against what you assumed to be true before you started the experiment." About this episode Dr. Pluznick discovered that olfactory receptors in mice are also expressed in their kidneys and blood vessels. Her research is focused on the role of chemosensory GPCRs in regulating renal and cardiovascular function, and identifying renal/cardiovascular olfactory receptor ligands, and relating them to whole-animal physiology. This work contributes to a better understanding of how the kidney helps maintain homeostasis in humans. Jennifer is currently an assistant professor of physiology at the Johns Hopkins School of Medicine. She received her undergraduate degree in biology from Truman State University and earned her Ph.D. in renal physiology from the University of Nebraska Medical Center. She then spent five years training as a postdoctoral fellow in the laboratory of Michael Caplan at Yale University, where she studied both renal physiology and sensory biology systems and focused on olfaction. Dr. Jennifer Pluznick on the web John Hopkins Pluznick Lab Pubmed Ted Talk 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 >>

Get one year of free Dr. GPCR Premium access for your entire academic lab. Teach a course at Dr. GPCR University and unlock expert resources, training, and tools. Academic Team Access Program One Year of Dr. GPCR Premium — Free for Your Entire Lab Empowering academic discoveries with industry-grade GPCR resources. Why We Created This Program? Your research group plays a critical role in advancing GPCR science. We want to support academic labs with the same high-quality tools, courses, and insights used by leading biotech teams—without financial barriers. The Dr. GPCR Academic Team Access Program gives your entire lab one year of Premium membership at no cost, in exchange for contributing to the community’s shared knowledge base through teaching . How does it work? No Cost, No Hidden Requirements The program is 100% free for academic labs who contribute as instructors. No recurring charges. No credit card required. Your Whole Lab Gets One Year of Premium Access Once approved, every member of your team receives free Premium access for 12 months, including: Full access to Dr. GPCR Masterclasses & University Vault Weekly News extended editions Exclusive event recordings, slides, and community decks Premium research insights and ecosystem reports Priority access to certain events and AMAs A Member of Your Lab Teaches at Dr. GPCR University Contribute your expertise by teaching a topic, workshop, or course within the Dr. GPCR University. Format is flexible — we work with your availability. Become part of the Dr. GPCR University Instructor community Learn More & Join the Program To keep things simple, we created a single guide that covers: Eligibility guidelines Teaching formats & examples Instructor expectations Course creation support Application steps Timeline & onboarding What your team receives Renewal options 👉 Everything is explained here *This link takes you to a dedicated page with all the details. Book Ready to Unlock Premium for Your Entire Lab—At No Cost? 👉 Learn More & Get Started Meet directly with Dr. Yamina Berchiche for a focused strategy conversation to align your goals, uncover opportunities, and map your next steps.

Explore Martin Marro’s impact on GPCR drug discovery, assay innovation, and translational pharmacology bridging academia, pharma, and biotech. << Back to podcast list Strategic Partner(s) GPCR Assay Strategy, Bias, and Translational Drug Discovery This episode features Dr. Martin Marro, currently Executive Director and Head of Cell Pharmacology at Eli Lilly’s Obesity Research Group. Dr. Marro’s career spans big pharma and biotech, encompassing functional assay development, GPCR internalization research, and both small molecule and biologic drug discovery. He discusses his formative scientific experiences, critical decision points moving from academia into industry, and his role leading and shaping multidisciplinary teams for screening and innovative therapeutics targeting metabolic and cardiovascular diseases. The conversation explores the realities of using fluorescence-based assays, the challenge of translating in vitro pharmacology to in vivo models, lessons on bias agonism, and novel approaches in antibody discovery for GPCR targets. Dr. Marro’s path highlights the strategic and methodological pivots essential for driving projects into the clinic. For a deeper dive into modern GPCR research and tools, explore more episodes of the GPCR Podcast and discover Dr. GPCR Premium resources. Why This Matters? How advanced assay design is essential for translating cell-based GPCR signals to therapeutic outcomes. Why strategic flexibility in exploring non-canonical signaling pathways is critical for GPCR-targeted drug discovery. What learning from “failed” screens can reveal about receptor pharmacology and species selectivity. The moment when bias agonism and receptor trafficking concepts shifted industry standards for functional assays. How integrating antibody-based modalities has expanded options for hard-to-drug GPCR targets. Why persistent scientific questioning and collaborative networks accelerate GPCR innovation across disease areas. Who Should Listen? This episode is relevant to anyone navigating the complex landscape of GPCR research and translational pharmacology. Those facing disconnects between in vitro functional data and in vivo efficacy in GPCR programs. Researchers refining strategies for high-throughput screening or exploring biased signaling. Teams expanding into antibody or biologic modalities for challenging GPCR targets. Scientists seeking practical advice on career pivots between academia, pharma, and biotech. About Martin Marro Dr. Martin Marro leads the Cell Pharmacology group in the Diabetes, Obesity and Complications Therapeutic Area at Lilly's Seaport Innovation Center in Boston. His scientific training included a PhD at the International Center for Genetic Engineering and Biotechnology, followed by an industrial postdoctoral fellowship at GSK, where he entered the GPCR field and became proficient in aptamer selection and cell signaling assays. Dr. Marro’s career advanced through roles at Novartis and Tectonic Therapeutic, contributing to projects across key therapeutic areas—spanning metabolic, cardiovascular, and gastrointestinal diseases. With over two decades in drug discovery, he has established expertise in early phase functional assay development, small molecule and biologics research, and team leadership through high-profile programs. Awarded patents and a proven record in both target and pathway identification, his drive centers on integrating rigorous pharmacology with translational impact while cultivating innovation and scientific growth within his teams. Guest on The Web LinkedIn 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) Robert Laprairie About Dr. Robert Laprairie Dr. Robert Laprairie is an Associate Professor and the Saskatchewan Research Chair in Drug Discovery and Development in the College of Pharmacy and Nutrition at the University of Saskatchewan. The focus of his research is the molecular pharmacology of cannabinoids and cannabinoid receptors. He was the 2018 and 2021 recipient of the Young Investigator of the Year Awards from the British Pharmacological Society and International Cannabinoid Research Society (ICRS), respectively. In 2019 he became the Director of Education for the Canadian Consortium for the Investigation of Cannabinoids (CCIC) and now also serves as the organization’s President. Dr. Robert Laprairie on the web University of Saskatchewan Twitter Instagram ResearchGate 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) 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 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 >>

How a bell-shaped FSH dose-response curve led to one of the earliest demonstrations of biased GPCR signaling - and a decade of pushback from the field. << Back to podcast list Strategic Partner(s) Brian Arey: Discovering Signaling Bias at the FSH Receptor Biased signaling - the idea that a single receptor can preferentially activate one downstream pathway over another depending on how it is engaged - is now a central concept in GPCR pharmacology and drug design. But for the researcher who first encountered it not as a theory but as an anomalous bell-shaped dose-response curve in an FSH receptor assay, it arrived as a problem that needed explaining. Brian Arey, Director of Mechanistic Pharmacology at Bristol-Myers Squibb, traces the origins of that discovery to a glycosylation difference between pituitary-purified and insect-cell-expressed FSH - a difference that turned out to encode physiologically distinct signaling outputs. The broader argument Arey has spent his career developing is that biased signaling is not a GPCR-specific phenomenon but an evolutionarily conserved principle present across all receptor classes. That argument eventually became a book, co-authored with Terry Kenakin, that Arey dedicated to his children - not because they are scientists, but because he wanted them to understand what he spent his life doing and why it mattered. ABOUT THE GUEST Brian Arey is Director of Mechanistic Pharmacology within the Discovery and Optimization organization at Bristol-Myers Squibb, where he leads research spanning GPCR pharmacology, enzymology, and protein homeostasis pathways. A physiologist by training, he completed his doctoral work on circadian regulation of prolactin secretion at Florida State University before postdoctoral research at Northwestern, and has spent over 25 years in pharmaceutical drug discovery across Wyeth and BMS. His early work at Wyeth's Women's Health Research Institute produced foundational observations on biased signaling at the FSH receptor, which were among the first experimental demonstrations that a GPCR could signal through parallel G protein pathways in a ligand-dependent manner. He is the author of a 2014 book on evolutionarily conserved receptor signaling, co-written with Terry Kenakin and published through Elsevier. SCIENTIFIC THEMES OF THE CONVERSATION Biased signaling at glycoprotein hormone receptors - the experimental origin Glycosylation isoforms as physiological regulators of differential receptor signaling Evolutionary conservation of biased receptor function across receptor classes The physiologist's approach to mechanistic drug discovery The erosion of pharmacology training in pharmaceutical research - and why it matters Career navigation across academia, industry, and the blurring boundary between them KEY INSIGHTS FROM THE CONVERSATION The bell-shaped curve was a hypothesis, not an artifact When insect-cell-expressed FSH produced a bell-shaped dose-response curve instead of a sigmoidal one, the obvious interpretation was contamination or a production problem. Arey treated it as a signal. The glycosylation difference between the recombinant material and pituitary-purified FSH had altered the receptor's downstream signaling profile - and the bell shape was the read-out. It took a pertussis toxin experiment, borrowed conceptually from Tom Burris's dopamine receptor work, to demonstrate that FSH receptor was signaling through both Gs and Gi simultaneously, and that the two glycoforms were biasing the system differently. Forty years of unresolved biology had a signaling answer The existence of multiple glycosylated isoforms of FSH, LH, and other glycoprotein hormones had been recognized for decades, but their physiological significance was not understood. Arey's data offered a functional explanation: different glycoforms stabilize different receptor conformations, which recruit different intracellular effectors with different affinities, driving different physiological outcomes in target cells. What had looked like biochemical noise in circulating hormone pools was, in this framework, a mechanism for fine-tuned signaling control. If the controls are right, the data has to be trusted When a substantial portion of the literature responded to Arey's published data by calling it wrong, he called his graduate advisor. The advice he received - that if all controls have been run appropriately and the result still holds, you have to have confidence in your data - has remained his operating principle for three decades. That conviction did not resolve the argument quickly. The field took nearly a decade to come around. But the data held. Biased signaling is not a GPCR specialty - it is a conserved principle The central argument of Arey's 2014 book is that the bimodal structure of receptor signaling - a ligand-binding pocket with one inherent affinity, and a cytoplasmic effector-binding pocket with its own independent affinity, both modulated by the conformational state the ligand stabilizes - is not unique to GPCRs. The same logic applies to cytokine receptors, nuclear hormone receptors, and receptor tyrosine kinases. Arey arrived at this hypothesis in the mid-1990s, before the structural and mechanistic data existed to support it, and spent years watching the field gradually produce that evidence. Techniques are tools in a toolbox - not endpoints One of the formative intellectual influences Arey credits from his graduate training is the principle that no technology is intrinsically interesting - it is only interesting insofar as it can answer a scientific question. That orientation shapes how he runs his team at BMS: a healthy skepticism toward established methods, including antibody-based assays that he views as 50-year-old technology capable of improvement, and a standing question of whether the current tool is actually capturing the biology being studied. Drug discovery needs modulators more than it needs hammers Arey's philosophy of drug discovery is grounded in a view of human physiology as inherently variable - shaped by evolution, divergent across populations, and rarely susceptible to single-target solutions. He argues for a therapeutic strategy built around modulators that can be combined, rather than single agents designed to dominate a pathway. That argument is not abstract: it is the conclusion of someone who has watched large programs fail to find silver bullets in multifactorial diseases for 25 years. EPISODE TIMELINE Timestamps are AI-generated from the transcript and may not perfectly reflect final edited audio. Verify against the published episode before using for navigation. 00:00 Introduction 01:48 Career overview - 25 years in drug discovery at Wyeth and BMS 06:03 Origin story - glassware, the first binding assay, and the decision not to become a physician 11:54 Graduate school - independently discovering a circadian rhythm regulating prolactin secretion still cited 30 years later 17:57 Leaving academia for Wyeth - a two-week decision, $18,000 a year, and the door that closed behind it 19:55 The FSH receptor anomaly - how a production shortcut produced the first experimental evidence of biased GPCR signaling 23:40 When the literature called the data wrong - holding the line for nearly a decade 30:41 The physiologist's lens - why Arey has never chased the trending field 35:00 Science, family, and the years he was a single father of two young children 40:35 Writing the book with Kenakin - the argument that biased signaling is evolutionarily conserved, and why he chose a book over a review 48:09 Dinner with Martin Rodbell - drawing the FSH data on a napkin and hearing "I'm not surprised" 53:07 Advice for scientists - follow the data, trust your controls, stay humble, give back 01:01:55 What pharmacologists bring to drug discovery that nobody else does SELECTED QUOTES "If you've done all the controls appropriately, and you've done the experiments to the best of your ability, and you've asked all the hard questions and you still get the same result, then you have to have confidence in your data." "What we study in pharmacology, whether it's a GPCR or whatever, what we're really studying is evolution at the base level. And when you think about it from that perspective, it's hard not to be awed by nature." "I'm not surprised." - Martin Rodbell, upon being shown Arey's FSH signaling data drawn on a dinner napkin, citing a 1972 paper in which Rodbell had proposed a similar mechanism. "Science is really a personal endeavor - it's creative and personal. I hate to say it because it's so overused, but it really is an art form and everybody approaches it differently." About this episode Brian Arey is Senior Director of Mechanistic Pharmacology within Leads Discovery and Optimization at Bristol-Myers Squibb Co . in Lawrenceville, NJ. He obtained both his MS and Ph.D. in Neuroendocrine Physiology at Florida State University before completing his postdoctoral training at Northwestern University. He then moved to work in the pharmaceutical industry where he has held positions of increasing responsibility. He currently leads a team that provides a mechanistic understanding of small molecule drug candidates across the entire portfolio of BMS. Brian has contributed to the discovery or development of 5 marketed drugs through his work spanning molecular, biochemical, cellular, and in vivo assessment of drug candidates in many different physiological systems. Dr. Arey’s laboratory discovered the first described synthetic agonists and antagonists of the FSHR and has been an early champion of signaling bias as a physiological mechanism of gonadotropin action. He continues to pioneer in drug discovery studying GPCRs and other target classes. His recently published book on signaling bias, Biased Signaling in Physiology, Pharmacology, and Therapeutics is available on Amazon . I sat down with Brian to chat about GPCRs, working in the industry, and being a leader. This is part 1 of our conversation. Dr. Brian Arey on the web LinkedIn ResearchGate Pubmed Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

A conversation with Prof. David Hodson on visualizing GLP-1 and GIP receptors in pancreatic islets and brain circuits to advance GPCR-targeted therapies for diabetes and obesity. << Back to podcast list Strategic Partner(s) Visualizing GLP-1 & GIP Receptors in Islets and Brain In this episode, Professor David Hodson discusses how GLP-1 and GIP receptors regulate metabolism across the pancreas and brain, and why visualizing receptor localization and signaling in real tissues is essential for advancing GPCR drug discovery . His team develops fluorescence-based and chemically engineered tools to study gpcr internalization and ligand engagement in intact islets and neuronal circuits — insights that inform next-generation functional assay development and translational therapeutic design. The conversation also highlights the role of interdisciplinary collaboration in accelerating innovation in diabetes and obesity research. Why this matters How receptor distribution in islets and brain circuits shapes incretin hormone drug effects Why visualization tools changed our understanding of GPCR signaling in metabolic tissues What collaborative chemistry enabled in designing receptor-targeted fluorescent ligands The moment when structural and imaging evidence clarified unexpected glucagon-derived peptide behavior How future metabolic therapies may evolve based on receptor cross-talk and tissue-specific engagement Who should listen Navigated complex datasets where interpretation depended on biological context Balanced innovation with the need for reproducible, well-controlled functional assays Worked across disciplines where chemistry, pharmacology, and physiology converge Questioned how drug action differs in real tissues vs. recombinant cell lines …this episode will resonate. About David Hodson Prof. David Hodson is the Robert Turner Professor of Diabetic Medicine at the University of Oxford , working within the Oxford Centre for Diabetes, Endocrinology and Metabolism. Originally trained as a Veterinary Surgeon , he completed postdoctoral research at the CNRS in Montpellier before establishing his independent laboratory at Imperial College London as a Diabetes UK RD Lawrence Fellow. He later served as Professor of Cellular Metabolism and Institute Deputy Director at the University of Birmingham. His group develops imaging and chemical biology tools to reveal how GLP-1 and GIP receptors operate within complex tissues, with direct relevance to type 2 diabetes and obesity therapy . David Hodson on the Web Radcliffe Department of Medicine Islet Biology Lab University of Birmingham 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 >>

Chris Tate co-founded Heptares after reading one paper on a Friday afternoon. This conversation covers thermostabilization, cryoEM, and GPCR structural biology. << Back to podcast list Strategic Partner(s) Chris Tate: Thermostabilizing GPCRs for Structural Biology For most of the 1990s and early 2000s, GPCR structural biology was not a biology problem - it was a stability problem. Receptors that fell apart in any useful detergent could not be crystallized, and without crystals, there were no structures. Chris Tate spent years working on membrane proteins that were simply too unstable to study by crystallography, and the question of how to solve that became the organizing problem of his career. The answer came from an unexpected source: a paper on thermostabilization of an unrelated membrane protein, read on a Friday afternoon in the library. That insight led to a systematic mutation screen, a 21-degree improvement in receptor thermostability, and eventually the co-founding of Heptares - a company now running over 250 GPCR structures and six clinical candidates. This conversation covers how thermostabilization changed what was structurally possible, how cryoEM then redrew the map again, and what the first solved Class D GPCR dimer reveals about receptor architecture at its most unexpected. ABOUT THE GUEST Chris Tate is a group leader at the MRC Laboratory of Molecular Biology in Cambridge, UK, where his research focuses on the structural and biochemical study of membrane proteins, with particular emphasis on GPCRs. His work developed the thermostabilization platform - a systematic approach to engineering receptor stability for structural biology - that enabled the first high-resolution crystal structures of multiple GPCRs in defined conformational states. He co-founded Heptares (now Sosei Heptares) in 2007, a company that has since produced over 250 GPCR structures and advanced six candidates into clinical trials. His current structural work extends to Class D GPCRs, including the recently solved first dimer architecture in this receptor family. SCIENTIFIC THEMES OF THE CONVERSATION Membrane protein instability as the overlooked bottleneck in GPCR structural biology The thermostabilization platform - from concept to systematic mutation screen From academic discovery to co-founding Heptares: decision, funding, and growth CryoEM and the conformational states that crystallography could never access Class D GPCR architecture - what a dimer with no prior blueprint looks like What remains unsolved: why drug discovery still fails in late-stage clinical trials KEY INSIGHTS FROM THE CONVERSATION Stability, not biology, was the bottleneck The reason GPCR structures took so long was not scientific complexity - it was that the receptors destroyed themselves in every detergent needed for crystallography. Tate's work reframed the problem: before asking what a receptor does, you first have to ask whether it can survive the conditions required to study it. A Friday afternoon and a paper on an unrelated protein The thermostabilization insight did not come from the lab. It came from Tate's habit of spending Friday afternoons in the library reading outside his immediate field. A 1999 paper on thermostability of diacylglycerol kinase - a protein with no connection to GPCRs - produced a light-bulb recognition that reshaped his entire research direction. 21 degrees changed what was chemically possible Thermostabilizing the beta-adrenergic receptor by 21 degrees Celsius was not a marginal improvement. It meant the receptor could survive in harsh short-chain detergents that had previously killed it instantly - including SDS. That stability was what made crystallization tractable and what became the foundation of Heptares. CryoEM opened conformational space that crystallography had locked out The arrestin-coupled state of a GPCR - a structure that required the agonist-bound receptor to be held in its active conformation - could never have come from crystallography. CryoEM removed that constraint, and Tate argues the field is still at the beginning of what this means: inactive-state structures, full conformational sets, and throughputs that were previously inconceivable. A Class D GPCR dimer with no prior blueprint The first solved structure of a Class D GPCR - a yeast receptor from family D - turned out to be a dimer, with an architecture that breaks the rules of class A receptor biology. The dimer interface sits on helix 1, involves a domain-swapped N-terminus and helix 7, is twice the area of the G protein coupling interface, and positions helix 4 over 20 angstroms from where it appears in any known class A receptor. A PhD student solved it in under two years. Drug discovery's real bottleneck is not structural Tate is direct about where the field now stands: accumulating GPCR structures is no longer the limiting step in drug discovery. The harder problem is understanding the human body well enough to predict why a compound that works in vitro fails in Phase 2 or Phase 3 - and solving that will require tools and systems that structural biology alone cannot provide. Science requires a skin like a rhino Tate's advice to young scientists is not procedural - it is temperamental. Science is brutal, things fail for months, and the only way through is genuine passion for being in the lab. He still asks every candidate who wants to join his group one question: do you know, in chemical terms, how a miniprep kit works? The answer reveals whether someone is curious about science or merely using it. EPISODE TIMELINE Timestamps are AI-generated from the transcript and may vary slightly from the final edited audio. 01:35 Meet Tate - membrane protein biochemist, MRC LMB 02:12 Career origin: from calcium ATPase to bacterial transporters 13:52 Path into GPCRs - instability as the bottleneck nobody was solving 17:00 The Friday afternoon library paper that changed GPCR structural biology 24:21 Thermostabilizing the beta receptor by 21 degrees - in any detergent, including SDS 25:56 Co-founding Heptares - the canteen conversation and the venture capital meeting 32:02 Raising £21M during the 2009 financial crisis 37:43 The cryoEM revolution - why the arrestin-coupled structure could never have come from a crystal 45:17 Unpublished: a Class D GPCR dimer - one PhD student, 18 months, a Nature paper 49:05 Advice for young scientists: what it actually takes to survive science 54:35 The curiosity test: do you know how your miniprep kit works? 58:34 Three aha moments - a diffraction pattern, a thermostabilization screen, and a synchrotron SELECTED QUOTES "None of my best ideas have ever arisen from being in the lab. Never. Because when you're in the lab, you're thinking about what's in front of you." "I don't think ever in my life I will ever write an application and just produce so much more than what I wrote in the original application." "Science is brutal. It is absolutely brutal. Things don't work for months. You have to be robust, you have to have a skin like a rhino sometimes." "When you see the GPCR field, all you see is this accelerating number of structures and information, and that is just going to get faster and faster. And I think that is now the minor part." About this episode Dr. Chris Tate obtained his Ph.D. from the University of Bristol in 1989 and then moved to the University of Cambridge (Dept. of Biochemistry) to work on bacterial sugar transporters. After obtaining a research fellowship at Girton College (Cambridge) he moved to the LMB in 1992 to work in Richard Henderson's group on the serotonin transporter. Chris also worked on the E. coli multidrug transporter EmrE and obtained both 2D and 3D crystals as well as a 3D structure using cryo-EM. In 2005 he started working on the development of conformational thermostabilization of GPCRs, which resulted in the structure of the β1-adrenoceptor. Subsequent work has focused on understanding the molecular basis of GPCR pharmacology through structure determination of the β1-adrenoceptor and adenosine A2A receptor in multiple different conformations bound to ligands of different efficacy. In 2016 mini-G proteins were developed as a tool for the structure determination of GPCRs in the fully active state. Structures have been determined by X-ray crystallography of receptors coupled to either mini-Gs or mini-Go, and also by electron cryo-microscopy of receptors coupled to mini G protein bound to βγ subunits. Recent work includes the first structure determination of a GPCR bound to a biased agonist and coupled to arrestin and also the first structure of a Class D receptor. Join me to learn more about Chris’s work and his role in founding Heptares which was later acquired by Sosei and became Sosei Heptares . Dr. Chris Tate on the web LinkedIn ResearchGate Pubmed Google Scholar Sosei Heptares Wikipedia MRC Laboratory of Molecular Biology 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 >>

From chemokine receptors at Rockefeller to founding Dr. GPCR during COVID — the career arc behind the ecosystem built for the field's unreached receptors. << Back to podcast list Strategic Partner(s) Yamina Berchiche: Beyond the Lab — From Chemokine Receptors to the Dr. GPCR Ecosystem Dr. Yamina Berchiche spent two decades working on G protein-coupled receptors at the bench — training that spanned chemokine receptor conformational dynamics at the Université de Montréal, CXCR3 splice-variant signaling at Rockefeller University in Dr. Tom Sakmar's lab, CRISPR knockout generation at NIAID, and class B peptide receptor work at Generate Biomedicines. Across those stops, one observation kept resurfacing: the GPCR field is enormous — roughly 400 non-olfactory receptors — but clinical drug discovery has reached only about 166 of them, leaving more than 250 receptors unstudied at anything close to therapeutic depth. This conversation traces the scientific arc that led Dr. Berchiche to leave the bench after a COVID-era redundancy, and examines the motivation behind founding Dr. GPCR — an ecosystem of podcasts, newsletters, summits, and working spaces designed to give the field connective tissue it has historically lacked. For Dr. Berchiche, this work is personal: the receptors she helped characterize for years belong to a family she believes has been collectively underserved by the infrastructure around it, and building that infrastructure has become a full-time scientific question in its own right. About the Guest Dr. Yamina Berchiche is the founder of the Dr. GPCR ecosystem and the host of the Dr. GPCR Podcast. She holds a PhD in Biochemistry from the Université de Montréal, where she trained in Dr. Nikolaus Heveker's lab at the CHU Sainte-Justine Research Center on chemokine receptor structure–function relationships, with extensive collaborative work in Dr. Michel Bouvier's lab on BRET-based conformational readouts. She completed postdoctoral training at Rockefeller University in Dr. Tom Sakmar's lab, where she characterized the signaling diversity of three alternative splice variants of CXCR3. Her career has moved through academic pharmacology, a research fellowship in B-cell molecular immunology at NIAID, and a senior scientist role at Generate Biomedicines, where she worked on class B peptide receptor engineering using AI-driven protein design. She now builds scientific community infrastructure for the GPCR field. Scientific Themes of the Conversation Chemokine receptor redundancy and the shift toward functional selectivity as a framework Splice variants as signaling variants — CXCR3 as a case study for transcript-level diversity The orphan-majority problem in GPCR drug discovery — why ~250 non-olfactory receptors remain outside clinical attention Career architecture for bench pharmacologists moving beyond academia and biotech Scientific community as infrastructure — what connective tissue a 400-receptor field actually needs Assay design as the lever that shifts conceptual frameworks Key Insights from the Conversation Rejection as redirection. The summer placement Dr. Berchiche didn't get in Michel Bouvier's lab led her to Nikolaus Heveker's newly opened lab at CHU Sainte-Justine, where she was the first student. The lab had no equipment, only stacks of bills on every bench — and a research program on chemokines and chemokine receptors that would define her career. The redundancy assumption crumbled under better assays. The chemokine system — roughly 50 ligands for 20 receptors — was framed for decades as redundant because multiple chemokines bind multiple receptors. Dr. Berchiche's thesis work on CXCR4 mutants and her PhD characterization of natural chemokines binding CCR2B showed the opposite: distinct ligands activate distinct signaling outputs, and functional selectivity was quietly hiding inside what had been called promiscuity. Splice variants aren't just structural — they signal differently. Her Rockefeller work on the three alternative splice variants of CXCR3, initially prompted by a simple question from Tom Sakmar, demonstrated that variants encoded by the same gene can recruit different signaling outputs in response to the same ligands. The implication: transcript-level diversity is itself a signaling mechanism, not a cloning artifact to be collapsed away. The 250-receptor problem sits in plain sight. Of roughly 400 non-olfactory GPCRs, only about 166 are being targeted or studied for clinical application. The remaining 250+ are not obscure — they are simply not connected to drug-discovery momentum. This gap, visible in the 2017 mapping work by Dr. Alexander Hauser and colleagues, is the motivating tension behind Dr. GPCR. The 30,000-foot view requires leaving the bench. After nearly two decades in the lab, Dr. Berchiche found that deep focus on one project was no longer fulfilling. The bench scientist's perspective — which she explicitly values — comes at the cost of the field-level view that ecosystem-building requires, and choosing between them turned out to be a real career architecture decision rather than a detour. Community is scientific infrastructure, not marketing. A podcast, a monthly newsletter, and a virtual summit are not promotional surfaces. They are the connective tissue a 400-receptor field uses to exchange techniques, ideas, and trust across institutional boundaries. Without that tissue, GPCRs stay siloed by receptor family and by lab. Building during a pandemic is a design constraint, not a footnote. Dr. GPCR was founded in March 2020 after a COVID-era redundancy at Generate Biomedicines. Early episodes were recorded in a Toyota Prius parked outside a gym with public Wi-Fi, and then in a closet studio her husband built so she could keep the AC running without bleeding background noise into the audio. The ecosystem's physical origins are inseparable from its founding conviction. Episode Timeline Timestamps were generated using AI for readability. 00:00 Introduction 02:25 The closet studio and what's in the talk 04:00 From Oradea to Montreal — the geography of a GPCR career 06:30 An empty lab and the chemokine redundancy problem 09:00 A master's, old-school molecular biology, and an accelerated JBC paper 11:00 CCR2B, functional selectivity, and a stellar reviewer moment 14:00 Rockefeller, CXCR3, and three splice variants that weren't the same 17:00 NIH and the pull toward a 30,000-foot view of the field 21:00 COVID, redundancy, and the 250 GPCRs nobody studies 23:08 Building the Dr. GPCR ecosystem 32:28 Q&A — preparing an episode, funding, and what's next 46:53 Recording Brian Roth from a Prius — the closet-studio origin story Selected Quotes "You have 400 non-olfactory GPCRs. Only about 166 of them are being targeted and studied for clinical applications. But you have 250-plus receptors that are not well characterized enough and are not considered for the treatment of any diseases." "If you want to advance the field and you want to drug GPCRs better, the point is not to show that you can pipette, but the point is to get to that result." "At NIH, I decided that I wanted to go what you'd call the dark side, which I don't think it's the dark side." "Brian throughout his career was told so many times that he should quit science. And thank God he did not quit science. That's the kind of story that I like to share in the podcast." About this episode GPCRs have played a central role in my scientific career ever since I took Dr. Michel Bouvier’s class as an undergraduate student at the University of Montreal in early 2000. During the past 2 decades, my research mainly focused on chemokine receptor structure/function relationships. For the purposes of this presentation, I will walk you through my various career experiences and include the skills I learned during each experience, which ultimately led me to found Dr. GPCR. Last, I will give an overview of the various programs we established at Dr. GPCR, present our team as well as provide you with a sneak peek of our future podcast guests and more. I gave a talk on October 12th at the 3rd ERNEST meeting about the Dr.GPCR Ecosystem . I want to say thank you to the ERNEST meeting organizers for the invitation with special thanks to Dr. Martha Summer and Dr. Alexander Hauser , and Luise Wagner . For more information about the ERNEST network, visit https://ernest-gpcr.eu/ . Dr. Yamina Berchiche on the web D r. GPCR Ecosystem Member Website LinkedIn Publications 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 >>

<< Back to podcast list Strategic Partner(s) Dr. Arthur Christopoulos About Dr. Arthur Christopoulos " Arthur Christopoulos is the Professor of Analytical Pharmacology and the Dean of the Faculty of Pharmacy & Pharmaceutical Sciences, Monash University, Australia. His research focuses on novel paradigms of drug action at GPCRs, particularly allosteric modulation and biased agonism, and incorporates computational and mathematical modelling, structural and chemical biology, molecular and cellular pharmacology, medicinal chemistry, and preclinical models of behaviour and disease. His work has been applied to studies encompassing neurological and psychiatric disorders, cardiovascular disease, obesity, diabetes, chronic pain and addiction. He has received substantial, long-term support from international and national competitive, charitable and commercial sources, as well as being academic co-founder of three GPCR-focussed biotechnology companies. Professor Christopoulos has over 360 publications, including in leading international journals such as Nature,Science and Cell, and has delivered over 180 invited presentations. He has served on the Editorial Board of 8 international journals and was a Councillor of the International Union of Basic and Clinical Pharmacology (IUPHAR). He has also been the recipient of multiple awards, including the John J. Abel Award and the Goodman and Gilman Award from the American Society for Pharmacology and Experimental Therapeutics; the Rand Medal from the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists; the British Pharmacological Society’s Gaddum Memorial Award; the IUPHAR Sir James Black Analytical Pharmacology Lecturer; the GSK Award for Research Excellence and a Doctor of Laws (Honoris Causa) from the University of Athens. Since 2014, Clarivate Analytics have annually named him a Highly Cited Researcher in ‘Pharmacology & Toxicology’, and in 2021 also named him a Highly Cited Researcher in the additional category of ‘Biology & Biochemistry’. In 2017, he was elected a Fellow of the Australian Academy of Health and Medical Sciences, in 2018 as a Fellow of the British Pharmacological Society, and in 2021 he was elected a Fellow of the Australian Academy of Science for his seminal contributions to drug discovery. In 2023, he was elected a Fellow of the Pharmaceutical Society of Australia. " Dr. Arthur Christopoulos on the web Monash University Wikipedia Google Scholar LinkedIn Dr. GPCR AI Summary AI-generated content may be inaccurate or misleading. Always check for accuracy. Quick recap Yamina and Arthur from Monash University discussed Arthur's career journey, the importance of hard work, failure, and differentiation in academic and personal lives, and the value of international conferences. They also explored the significance of translating fundamental discoveries into clinical applications, the potential of new drugs, and the unique challenges within universities. Additionally, they discussed the importance of hiring based on differentiation, impact, and interest, the need for workforce development, and the potential of involving junior scientists and postdocs in their podcast. Lastly, they touched upon the global challenges of healthcare workforce growth, climate change, and emerging psychiatric disorders, as well as the importance of recording lectures and making pre-lesson materials available to students. Next steps - Yamina will share notes about PRISM and presentability with Arthur. - Arthur will share the story of PRISM's development and its impact on the field with Yamina. - Yamina will send an invite for a follow-up meeting with Arthur next Saturday at 9 PM. - Arthur and Yamina will prepare for the next meeting, focusing on the concept of biased agonism and discussing Dr. GPCR and the charity status. - Yamina will attempt to book Denise for a future podcast episode. Summary Arthur's Career Journey and Transition to Dean Yamina introduced Arthur to her team and discussed the use of a particular tool for meeting summaries. Arthur shared his career journey from pharmacy to becoming a professor, highlighting the influence of his mentors and the importance of his postdoctoral experience. They discussed the value of hard work, failure, and the significance of differentiation in their personal and academic lives. Towards the end, they focused on Arthur's transition to become Dean and his decision to move from Australia to the United States for a postdoctoral position. Postdoctoral Position, Scientific Dynamics, and New Drug Targets Arthur shared his decision to undertake a postdoctoral position with Nigel Bird's lab in the UK and his experiences of meeting influential figures during his time in the US. He and Yamina discussed the importance of preserving original work, the value of international conferences, and the dynamics between junior and senior scientists in a research environment. They also shared their admiration for the work of a mutual friend and discussed the history of muscarinic receptors, specifically focusing on the role of a compound that Arthur received from Fred. Lastly, they discussed the progress of new drugs targeting specific receptors for various diseases, with Arthur sharing insights on Eli Lilly's compound, Xanomeline, and the potential of M4 PAM for psychosis. Collaborative Research and Translational Approach Arthur and Yamina from Monash University discussed their collaborative approach to scientific research, emphasizing the benefits of combining their complementary skills and interests. They shared their unconventional approaches to research, including the creation of a critical mass of GPCR researchers in Australia and the initiation of a successful series of conferences. They also discussed the relocation of some university labs to facilitate collaboration and overcome the siloed department structure. Additionally, they explored the unique culture and structure of their Institute, highlighting its translational approach to research and its capacity to translate research into therapeutic commercialization. Lastly, Arthur shared three significant moments that shaped his career, including the evolution and impact of analytical pharmacology, particularly highlighting the role of Prism, a data analysis tool. Podcast Format, Team Culture, and Science Yamina and Arthur concluded their discussion and decided to take a short break. They talked about the format and length of their podcast, their professional interests, and their recent successful bid to bring Moderna to their university. They also explored the idea of starting a similar talk show format to 'Between Two Ferns', the importance of maintaining team culture, and the potential health issues among well-known scientists. Lastly, they discussed the growth and development of the Monash Institute of Pharmaceutical Sciences, the importance of knowing when to let go in scientific experiments, and the idea of a panel for building and incubating companies. Arthur's Pandemic Journey and Global Challenges Yamina and Arthur discussed Arthur's experiences during the Covid-19 pandemic, his journey as a research fellow in Australia, and his transition to the role of Dean. Arthur shared his insights into the unique grant funding system in Australia, the importance of impact in research, and the challenges of balancing administrative responsibilities with scientific pursuits. He also reflected on his personal health struggles, the growth of his university, and the faculty's successful response to the Covid crisis. The conversation also touched upon Arthur's career decisions, his scientific achievements, and the importance of learning from mistakes and self-confidence. Lastly, they discussed the global challenges of healthcare workforce growth, climate change, and emerging psychiatric disorders, as well as the importance of recording lectures and having pre-lesson materials available to students. Translating Discovery Into Clinical Application Arthur and Yamina discussed the importance of translating fundamental discoveries into clinical applications in their research, highlighting the unique opportunities presented by their location and partnerships with other institutions. They stressed the necessity of making their research goals clearer, avoiding replication, and adopting a more assertive approach in grant applications. They also emphasized the significance of fundamental discoveries, the role of biotech, and the need for efficiency and process development in university systems. The conversation highlighted ongoing challenges within universities, including resistance to change and the need to communicate expectations and protect established cultures. Hiring Process, Collaboration, and Education-Focused Initiatives Arthur emphasized the importance of differentiation, impact, and interest in their hiring process and fostering a culture of collaboration. He shared his vision of breaking down barriers and promoting education-focused initiatives, encouraging his team to be innovative and apply their skills to education. Yamina expressed a desire to learn from successful leaders and the importance of recognizing talent and matching it with the needs of a particular project. They also discussed the disruption within the pharmaceutical sector, the importance of workforce development, and the need for maintaining a healthy work-life balance. Lastly, they deliberated on involving junior scientists and postdocs in their podcast and the possibility of writing a book about their experiences in academia. 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) GPCR location matters with Dr. Gabriele Kockelkoren About Gabriele Kockelkoren I have a strong background in both physics and molecular biology and, accordingly, I strive in interdisciplinary environments. After completing a cum laude BSc. and MSc. in Nanobiology at the Technical University of Delft in The Netherlands, I pursued a PhD at the University of Copenhagen under the supervision of Prof. Dimitrios Stamou. In my PhD, I studied the nanoscale spatial organization of G protein-coupled receptors (GPCRs) at the plasma membrane of living cells. Importantly, my work revealed heterogeneous spatial patterns of receptor density and activation, that are modulated in a drug-dependent manner. These findings identify nanoscale GPCR spatial organization as an integral element of their activity and signaling. Currently, I am a Postdoctoral Fellow in the lab of Prof. Alice Ting developing programmable receptors for molecular sensing and controlling cellular behaviour. Gabriele Kockelkoren on the web Stanford University X LinkedIn Google Scholar ORCID ResearchGate 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) The Role of Quantitative Sciences in GPCRs with Dr. Nagarajan Vaidehi About Dr. Nagarajan Vaidehi "Nagarajan Vaidehi, Ph.D., is professor and chair of the Department of Computational and Quantitative Medicine (DCQM) at the Beckman Research Institute of the City of Hope in Los Angeles, CA. She is also the Associate Director of the City of Hope Comprehensive Cancer Center. Dr. Vaidehi received her Ph.D. in quantum chemistry from the Indian Institute of Technology in India, where she was honored with the Distinguished Alumni Award in 2016. Following her postdoctoral studies on protein dynamics simulation methods at University of Southern California, and at Caltech, she became the director of biomolecular simulations at the Materials and Process Simulation Center, Beckman Institute at Caltech. Dr. Vaidehi joined the Beckman Research Institute of the City of Hope in 2006 as a Professor and became chair of DCQM in 2018. She has advanced the use of computational methods to meet the challenges of designing therapeutics with lower off target effects. She is an internationally recognized biophysicist for her contributions in developing constrained molecular dynamics simulation methods with emphasis on application to G-protein coupled receptors and drug design." Dr. Nagarajan Vaidehi on the web City of Hope 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. Yamina Berchiche About Dr. Yamina Berchiche Dr. Yamina A. Berchiche is the founder of Dr. GPCR, an ecosystem designed to bring together stakeholders interested in using G-Protein Coupled Receptors (GPCRs) that control virtually everything in the body as drug targets. The mission of Dr. GPCR is to accelerate GPCR drug discovery by sharing the latest research and technology advances in the field and providing exposure to scientists through the Dr. GPCR podcast. Dr. Berchiche obtained her Master’s and Ph.D. in Biochemistry at the University of Montreal in Canada before training at Rockefeller University in New York and the National Institutes of Health in Bethesda, Maryland. She developed expertise over the past two decades studying structure/function relationships of GPCRs using live-cell bioluminescence resonance energy transfer (BRET). Her work focused on chemokine receptors, members of the GPCR family that control cell movement in the body. Dr. Yamina Berchiche on the web Website LinkedIn Facebook Twitter ResearchGate PubMed Google Scholar Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>