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<< Back to podcast list Strategic Partner(s) Brendan Wilkins About Brendan Wilkins "Brendan completed his undergraduate training at the University of New South Wales (UNSW) Sydney, Australia in 2016 with first class Honours in Pharmacology. In his Honours year, Brendan explored small molecule allosteric modulators of the β2-adrenoceptor under the tutelage of Dr Angela Finch. Since then, Brendan worked as a research assistant at the Victor Chang Cardiac Research Institute where he investigated the orphan G protein-coupled receptor (GPCR), GPR37L1. Brendan is now a final year PhD candidate in the Orphan Receptor Laboratory headed by Associate Professor Nicola J Smith at UNSW Sydney, Australia. Brendan’s PhD project focuses on the orphan GPCR GPR146. This project aims to characterise the molecular pharmacology of GPR146 and to validate the proposed ligands of GPR146 in line with IUPHAR-NC guidelines on deorphanisation of orphan GPCRs. Brendan is currently looking for post-doctoral positions to begin in mid-2024" Brendan Wilkins on the web UNSW Sydney Google Scholar ResearchGate LinkedIn Twitter Dr. GPCR Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

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<< Back to podcast list Strategic Partner(s) Dr. Françoise Bachelerie About Dr. Françoise Bachelerie " FB leads a team at Paris-Saclay University with expertise in immunology and virology related to Host/Virus interactions and GPCR function. The team’s projects are devoted to the activation/function of CXCR4-ACKR3 (CXCR7) receptors of the CXCL12 chemokine, key effectors of the immune system, including their role in immunological disorders (e.g. WHIM syndrome) and in the innate control of the life cycle of papillomavirus, which are commensal inhabiting the healthy human epithelium (virome) while presenting an oncogenic potential that remains a major health concern. FB is recognized for her expertise and pioneering works in the field of biological and pathological functions of chemokines and their receptors, for which she made important breakthroughs regarding the CXCL12/CXCR4/ACKR3 trio. In particular, FB contributed to the discovery that CXCL12 is the ligand for the CXCR4 receptor and can therefore prevent infection by the Human Immunodeficiency Virus (HIV). FB’ team has identified the orphan CXCR7/ACKR3 receptor as being the 2nd receptor for CXCL12, which behaves as a modulator of CXCL12/CXCR4 functions. FB is a member of various international committees in the field, including the one that reviewed the standard nomenclature for chemokine receptors that are categorized into a large subgroup of G protein–coupled (GPCR) leukocyte chemotactic receptors (including CXCR4), and a smaller subgroup of atypical chemokine receptors (including the CXCR7/ACKR3). " Dr. Françoise Bachelerie on the web INSERM ResearchGate SciSpace Loop LinkedIn Dr. GPCR Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Stephen Ferguson The History of the Great Lakes GPCR Retreat with Dr. Stephen Ferguson About Dr. Stephen Ferguson Dr. Stephen Ferguson is a Professor in the Department of Cellular and Molecular Medicine at the University of Ottawa. He did B.Sc. in biology at McGill University and received his Ph.D. under the mentorship of Dr. Brian Collier in the Department of Pharmacology and Therapeutics at McGill University (1994). He did his postdoctoral training with Dr. Marc G. Caron at Duke University (1994-1997), where he and his colleagues investigated the role of G protein-coupled receptor kinases and beta-arrestin in regulating G protein-coupled receptor endocytosis, trafficking, and signaling. He has held four Canada Research Chairs since 2001 and was previously a Heart and Stroke Foundation of Canada MacDonald Scholar (1998-2003) and Heart and Stroke Foundation of Ontario Career Investigator (2003-2016). He was a recipient of Canada's Top 40 under 40 award in 2004 and received Queen Elizabeth II, Diamond Jubilee Medal, in 2012. He has also received both Junior (2001) and Senior (2005) investigator awards from the Pharmacological Society of Canada. Most recently, in 2021, he was elected as a Fellow of the Canadian Academy of Health Science (FCAHS). His research career has focused on the investigation of the regulation of G protein-coupled receptors signaling mechanisms in health and disease. He currently holds multiple research grants from the Canadian Institutes of Health Research (CIHR) for his research investigating the role of metabotropic glutamate receptor signaling in Huntington’s and Alzheimer’s disease. Dr. Stephen Ferguson on the web Carlton University Canada Research Chairs Twitter ResearchGate LinkedIn Dr. GPCR Ecosystem Great Lakes GPCR Retreat on the web 21st Great Lakes GPCR Retreat More about previous GPCR Retreat meetings Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Stephane Angers About Dr. Stephane Angers Dr. Angers is an expert in the field of signal transduction. He obtained his Ph.D. from the Université de Montréal in 2002 under the guidance of Dr. Michel Bouvier . His thesis work led to the development and application of light energy transfer methodology to study protein-protein interaction and signal transduction. From 2002-2006 he was a Howard Hughes Post-Doctoral Fellow at the University of Washington in Seattle under Dr. Randall T. Moon , where he identified and characterized novel components of the Wnt signaling pathway and a new class of E3 ubiquitin ligases . In October 2006, Dr. Angers established his independent research program in the Department of Pharmaceutical Sciences at the Faculty of Pharmacy and the Department of Biochemistry at the University of Toronto. He is the recipient of the Canada Research Chair in Functional Architecture of Signal Transduction. His research program is developed to understand the signaling mechanisms underlying the Wnt and Hedgehog families of growth factors and their signaling mechanisms in development, adult tissue homeostasis, and human diseases. His pioneer work led to the development of novel antibody molecules blocking and activating the Wnt pathway for the treatment of cancers and regenerative medicine applications. He is the scientific founder of two biotech companies, ModMab Therapeutics , and AntlerA Therapeutics , which are pursuing the clinical development of these molecules. In September 2021, Dr. Angers was named Director of the Donnelly Centre of Cellular and Biomolecular Research at the University of Toronto, an internationally recognized Research Institute bringing together multidisciplinary teams of scientists. Dr. Stephane Angers on the web Angers Lab The Donnelly Centre Twitter Dr. GPCR Ecosystem LinkedIn Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Nariman Balenga About Dr. Nariman Balenga "I received my Master’s degree from the University of Tehran, Iran, in 2005 by studying the suitability of nanoparticles as porters of DNA vaccination against allergens in mice. Then I pursued my education in the lab of Dr. Maria Waldhoer at the Medical University of Graz, Austria, and received my Ph.D. in Molecular Medicine in 2010 after studying the orphan atypical cannabinoid receptor, GPR55 and its crosstalk with CB1R and CB2R in endothelial cells and neutrophils. I followed my interest in allergy and GPCRs by joining the lab of Dr. Kirk Druey at NIAID/NIH, where I characterized the role of RGS4 and RGS5 in airway hyperresponsiveness and lung fibrosis in acute and chronic mouse models of allergic asthma. I was fascinated by the multitude of processes that are regulated/dysregulated by GPCRs and RGS proteins in the lungs of patients with asthma. At the height of curiosity, a seemingly naïve idea at the dinner table led to a side project by which I characterized the impact of a fungal allergenic source on the function of airway smooth muscle cells. A fungal serine protease allergen with GPCR-modulating features was discovered as a new biomarker and target in patients with severe asthma. In 2015 I joined the University of Maryland School of Medicine as an Assistant Professor. I studied the function of RGS5, calcium-sensing receptor, and an orphan adhesion GPCR, GPR64/ADGRG2 in parathyroid glands of patients with hyperparathyroidism and their impact on body calcium homeostasis and bone resorption in relevant transgenic mice. In 2021, I joined the Ferring Research Institute of Ferring Pharmaceuticals in San Diego as a scientist." Dr. Nariman Balenga on the web Researchgate Linkedin.com Google Scholar Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

GPCR scientist Ben Clements shares how positive allosteric modulators could transform opioid therapy by boosting efficacy and reducing side effects. << Back to podcast list Strategic Partner(s) When to Walk, When to Run: Lessons from the GPCR Trenches with Dr. Ben Clements The Power of Inclusion in the GPCR Field This episode kicks off with a celebration of early-career scientists. Host Dr. Yamina Berchiche emphasizes the importance of diverse voices in the GPCR community: “It’s been a very difficult path to get more early-career scientists on the podcast. But it’s important to make your voice heard.” Benjamin Clements , a postdoctoral fellow at the University of Michigan, joins the conversation as a rising voice in GPCR pharmacology. His journey highlights the transition from general drug development to a deep dive into G protein-coupled receptors. From Aspirations to Application: Ben’s Path into Science Ben shares his winding yet deliberate entry into science. Initially driven by a general passion for biology and a childhood dream of being an astronaut, he began with intestinal choline transport research at UNC. The realization that basic science could impact real patients was transformative. “It’s not just raw science — this can help someone at the end of the day.” – Ben Clements His pivot into neuroscience and pharmacology during grad school at the University of Minnesota laid the groundwork for his current work in GPCR pharmacology. GPCRs and the Opioid Crisis: A New Pharmacological Frontier Now at the University of Michigan, Ben focuses on positive allosteric modulators (PAMs) targeting opioid receptors. The goal: maximize analgesia while minimizing side effects . “We’re enhancing the powerful pain-relieving effects of opioids while limiting respiratory depression, constipation, and abuse liability.” He is particularly excited by the novel application of PAMs in chronic and neuropathic pain models , including the neuroma model , which is typically opioid-insensitive. Allosteric Modulation: The New Frontier of GPCR Drug Discovery Ben reflects on the emerging potential of allosteric modulation in GPCRs — a field that has lagged behind ion channels in clinical applications. “Allosteric modulation in GPCRs is so novel and so exciting. There’s so much availability, so much we don’t know yet.” By working with distinct chemical scaffolds like thiazolidines and xanthinediones, Ben is helping define how structurally different PAMs may act on similar receptor sites. Scientific Rigor: The Value of ‘Old School’ Pharmacology Despite the availability of modern tools, Ben stresses the enduring value of classical methods like GTPγS assays , radioligand binding , and basic PK/PD models . “It doesn’t matter how many cool, fun tools you have. If you don’t understand the math that underlies an allosteric modulator, you won’t understand what’s happening.” This mindset keeps his science grounded, reproducible, and rooted in fundamentals. Mentorship, Team Culture, and the Joy of Science Science is serious work, but Ben believes fun and collaboration fuel great outcomes. At Michigan, his lab balances rigor with light-hearted engagement — like daily squirrel trivia on their whiteboard. “Science is fun. We produce great data, but we also joke around. That’s how we work best.” Strong mentorship, open communication, and peer learning — especially from undergraduate trainees — shape his development as both a scientist and future educator. Translating Discovery into Therapy: Bench to Bedside Vision Ben’s work seeks to merge in vitro mechanistic data with in vivo efficacy , guiding medicinal chemists toward creating druggable PAMs . “The goal is to smash all the amazing biology together and make a drug.” Using site-directed mutagenesis and pharmacological synergy assays , his team aims to understand how and where these compounds interact with the receptor, paving the way for structure-based drug design . Structural Biology Roadblocks: The Cryo-EM Challenge One bottleneck in Ben’s work is visualizing binding sites of PAMs via cryo-EM , due to low compound potency and membrane-embedded binding pockets. “Our compounds don’t bind well enough to be seen clearly. That’s a real challenge with allosterics.” Still, by collaborating with structural biology teams and combining cryo-EM with NMR , his lab is narrowing down potential binding regions. Lessons in Confidence, Collaboration, and Aha Moments From asserting himself as an undergrad to mastering unique techniques in grad school, Ben has accumulated key “aha” moments that shaped his confidence: Standing up to big names when safety was compromised. Realizing his technical skills were indispensable to the team. Discovering breakthrough results in neuroma pain models via a spontaneous collaboration. “We found something incredible — a tenfold shift in the methadone dose-response with our PAM.” Advice for Junior Scientists: Read, Rest, Run Ben closes with wisdom for early-career researchers: “Academia is about knowing when to walk and when to run.” – Advice from Kelsey Flepsen He advocates: Reading one paper a day. Taking care of yourself when possible. Pushing hard when deadlines or breakthroughs demand it. “Your brain’s not a machine. Let it rest. That’s when the best ideas come — in the shower or on a walk.” Key Takeaway This Episode with Ben Clements is a deep dive into the pharmacological potential of GPCRs , the power of mentorship, and the mindset required to thrive in science. With clarity, curiosity, and a collaborative spirit, Ben reminds us that impactful science isn’t just about technology — it’s about people, persistence, and timing. “Science is all about knowing when to walk and knowing when to run.” About Ben Clements Dr. Ben M Clements is a behavioral pharmacologist who uses in vitro and in vivo models to discover and characterize novel treatments for chronic pain and opioid use disorder. He received his Ph.D. in Pharmaceutics from the University of Minnesota in 2022, studying the pharmacokinetics and pharmacodynamics of NMDA receptor antagonists. At the University of Michigan, Ben focuses on determining the mechanisms of action of a series of positive allosteric modulators of the mu-opioid receptor. This project involves molecular pharmacology in cell models to determine binding sites and mechanisms of allostery, as well as efficacy studies in mouse and rat models of acute and chronic pain. Dr. Clements' work is primarily focused on translational developments of small molecule therapeutics, and intends to apply these ideas to an independent academic laboratory. In addition, he plans to continue studying how neuromodulators, both exogenous and endogenous, can influence cellular activity, physiological behaviors, and human health. Ben Clements on the web University of Michigan X Google Scholar LinkedIn Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Join the Dr. GPCR Podcast community and shape our next season! Take our quick 5-minute audience survey to help us tailor our content to your needs. Your input matters in delivering exciting and informative episodes. Thank you for being part of our journey and for tuning in! Dr. GPCR Podcast Audience Survey Thanks for listening to this podcast episode Follow us on your favorite Podcast Player Be our Guest Listen and subscribe where you get your podcasts

mGlu2 can suppress drug seeking across four addictive substances - but its clinical results have never been published. Johnson explains why the circuit matters more than the receptor. << Back to podcast list Strategic Partner(s) Kari Johnson: mGlu2, Addiction, and the Brain Circuits Alcohol Rewires The brain circuits governing reward, motivation, and decision making are not fixed - they are continuously reshaped by experience. In alcohol use disorder and other substance addictions, one of the most consequential changes is the shift from goal-directed to habitual behavior: a state in which drug seeking persists not because of pleasure, but because the underlying circuit no longer responds to consequences. mGlu2, a presynaptic metabotropic glutamate receptor coupled to Gi/o proteins, sits at a critical junction in this process. By suppressing glutamate release across circuits in the basal ganglia, mGlu2 is positioned to modulate drug seeking, habit formation, and reward processing - and has been pursued as a potential therapeutic target in addiction, depression, schizophrenia, and Parkinson's disease. Kari Johnson's research follows this receptor from the bench to the behaving animal, using optogenetics and circuit-selective mouse models to ask which specific corticostriatal pathways are driving behavioral change after alcohol exposure - and whether pharmacological rescue is possible after those circuits have already been disrupted. The question has been central to Johnson's career since long before the tools to answer it properly existed. ABOUT THE GUEST Kari Johnson is an assistant professor of neuropharmacology at the Uniformed Services University of Health Sciences in Bethesda. Her lab investigates how GPCRs modulate synaptic transmission in brain circuits involved in reinforcement learning, with a particular focus on how chronic alcohol exposure disrupts those mechanisms across levels ranging from gene expression to neural circuit function to behavior. She trained in high-throughput drug discovery at Vanderbilt - contributing to early functional assay development for metabotropic glutamate and muscarinic receptors - before completing postdoctoral training at the National Institute on Alcohol Abuse and Alcoholism with Dave Lovinger. Her current work combines whole-cell patch clamp electrophysiology, optogenetics, and operant behavioral pharmacology to study mGlu2 function in specific corticostriatal circuits and its role in the transition from controlled to compulsive drug use. SCIENTIFIC THEMES OF THE CONVERSATION mGlu2 as a convergence target across addiction, psychiatric disease, and movement disorders Circuit-specific GPCR modulation and the "modulomics" framework Goal-directed versus habitual behavior as a mechanistic framework for understanding addiction Pharmacological rescue of alcohol-disrupted receptor function using positive allosteric modulators The translational gap: why a decade of preclinical mGlu2 evidence has not yet reached clinical success The limits of brain slice electrophysiology - and why optogenetics redefines the questions the field can ask KEY INSIGHTS FROM THE CONVERSATION mGlu2 Sits at the Center of Multiple CNS Disorders Because mGlu2 regulates glutamate release in brain regions linked to reward, executive function, motivation, and stress responses, it has become a target of interest across an unusually broad disease landscape - alcohol use disorder, schizophrenia, depression, Parkinson's disease, and multiple other substance addictions. That breadth is a signal of the receptor's centrality in CNS function. It is also a complication: a receptor that modulates so many circuits will inevitably produce wanted and unwanted effects that are difficult to predict from any single experimental system. Alcohol Disrupts mGlu2 - But a PAM Can Restore It Johnson's lab demonstrated that adolescent alcohol exposure disrupts mGlu2 function in the striatum in a way that might seem to close off therapeutic targeting - if the receptor is impaired, can it still be activated pharmacologically? Their answer was yes: a positive allosteric modulator restored mGlu2 signaling even after alcohol-induced disruption. This finding shifts the question from whether mGlu2 is a viable target in addiction to how to reach it once its function has already been compromised. The Years Before the Tools Existed For most of the history of GPCR electrophysiology, researchers used electrical stimulation in brain slices and could observe that a receptor modulated synaptic transmission - but not which specific set of synaptic inputs was responsible. For Johnson, this was a formative constraint she navigated across her entire training: drawn to circuit-level questions that her early tools could not fully answer, she made the shift to optogenetics and genetically defined neuronal populations specifically because the biology demanded it. The tools arrived late relative to the questions. That gap, in Johnson's framing, is both a limitation of the past and an argument for the field's current momentum. Modulomics: Naming the Question Changes What You Can Ask Johnson's postdoc mentor Dave Lovinger coined the term "modulomics" to describe the systematic study of circuit-specific neuromodulation by GPCRs - using light-activated ion channels expressed in anatomically or genetically defined neurons to isolate receptor effects at individual synaptic inputs rather than across an entire stimulated pathway. Giving the approach a name formalizes it as a research program, not just a technique. Johnson's lab has extended this using conditional knockout mice that allow selective deletion of mGlu2 from specific cell types, enabling circuit-level pharmacology with direct behavioral readouts. The Habit Framework Changes What Addiction Means Pharmacologically The shift from goal-directed to habitual behavior is not just a behavioral description of addiction - it implies a specific circuit mechanism. Goal-directed behavior is sensitive to changes in outcome value; habitual behavior is not. When alcohol exposure biases the brain toward habit formation, the circuit underlying that inflexibility becomes the pharmacological target. Johnson's lab uses this framework to ask whether activating mGlu2 in specific corticostriatal circuits can reverse the habit bias that chronic alcohol produces - not just dampen the pleasure of drinking, but restore the flexibility of the decision that precedes it. Clinical Trial Results for mGlu2 Ligands Have Not Been Made Public Johnson noted that multiple clinical trials testing mGlu2 ligands in substance use disorders - including for smoking cessation and cocaine use disorder - have been conducted and completed. The results have not been released to the research community. Without access to those data, researchers cannot determine why promising preclinical findings did not translate, cannot adjust future trial designs, and cannot evaluate whether the receptor was genuinely ineffective or whether confounds such as prior antipsychotic exposure were responsible - a hypothesis already supported by subsequent preclinical work following the disappointing schizophrenia trials. The gap is consequential, and Johnson named it directly. Translating GPCR Research May Require Releasing Attachment to Specific Receptors One of Johnson's more quietly contrarian observations is that attachment to a "favorite receptor" may be limiting translational success. If mGlu2 activation produces the desired circuit effect in rodents but not in humans, the value of that work is not lost - it defines the functional target. A different receptor capable of achieving the same circuit-level effect in a human brain might carry the therapy further. The question, in Johnson's framing, is not which receptor you prefer, but which receptor is correctly positioned in the human circuit you need to modify. EPISODE TIMELINE Note: Timestamps are AI-generated from the transcript and may require manual verification after video editing. 00:00 Introduction 01:27 Johnson's career path - from Vanderbilt drug discovery to NIH postdoc to independent lab 07:31 Alcohol disrupts mGlu2 in adolescent mice - and a positive allosteric modulator rescues it 09:45 Why mGlu2 is Johnson's receptor of focus: synaptic plasticity and long-term depression 11:26 mGlu2 and drug seeking: preclinical evidence across alcohol, cocaine, methamphetamine, and heroin 13:28 How mGlu2 modulates dopamine release and the neurobiology of habit formation 16:28 Optogenetics and modulomics - studying circuit-specific GPCR function in the basal ganglia 20:45 Operant behavioral models: how habit formation is measured in mice 25:25 Clinical trials for mGlu2 ligands - what advanced, what disappointed, and what remains unpublished 28:41 Are GPCRs still good drug targets? A circuit-level argument 33:12 Advice for junior scientists: let the biology lead the method 35:28 Diversity in STEM and who carries the labor of change SELECTED QUOTES "Even if we see that these experiences cause an impairment in receptor function, there might be pharmacological strategies that we can use to rescue that." "We're really just beginning to scratch the surface of understanding how these receptors work in specific neural circuits - and that has the potential to impact our understanding of how they influence a really wide range of behaviors, especially since mGlu2 is expressed in so many different brain areas." "Maybe the effect that I want to have by activating mGlu2 has the effects I want in a rodent brain, but doesn't have it in a human brain. But maybe there's another receptor there that will have the effect that we want in the human brain." "Let the science lead you. If you take that approach, you'll have plenty of moments where you realize that a new tool could take your research to another level. But there's no reason to force it just because you feel like you should be incorporating a popular technique." About this episode Dr. Kari Johnson is currently an assistant professor at the Uniformed Services University of the Health Sciences in Bethesda, Maryland. She is a neuropharmacologist with an interest in the long-term effects of alcohol abuse on neural circuits. Kari completed her Ph.D. in Pharmacology at Vanderbilt University before continuing her training as a postdoctoral fellow at the Vanderbilt Center for Neuroscience Drug Discovery, the National Institute of General Medical Sciences, and the National Institute on Alcohol Abuse and Alcoholism. All through her career, the recurring theme in Kari’s work has been GPCRs and more specifically Metabotropic Glutamate Receptors. Join me and learn more about how Kari studies GPCRs in basal ganglia circuits following chronic alcohol exposure in mice. Dr. Kari Johnson on the web LinkedIn Google Scholar Research Gate USU Twitter Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Timo De Groof About Dr. Timo De Groof Dr. Timo De Groof studied Biochemistry and Biotechnology at the University of Ghent where he graduated in 2015. During his master's studies, he specialized in Biomedical Biotechnology and Structural Biology/Biochemistry. During his last year of studies, Timo performed research in the biopharmaceutical company Argen X and gained experience in the identification and characterization of llama-derived antibodies in inflammatory diseases and oncology. From 2015 to 2019, he completed his Ph.D. in the Medicinal Chemistry group at VU University Amsterdam under the supervision of Prof. Dr. Martine Smit . During his Ph.D., Timo, together with Dr. Raimond Heukers , developed a nanobody platform within the research group and used this platform to develop nanobodies targeting viral G protein-coupled receptors with a special focus on the human cytomegalovirus-encoded chemokine receptor US28. During his Ph.D., he used these nanobodies as research tools, to investigate different GPCR conformations, while also focusing on their therapeutic potential in oncology and transplant infectious disease. Starting from September 2019, Timo started working as a postdoctoral researcher at the Vrije Universiteit Brussel in the In Vivo Cellular and Molecular Imaging (ICMI) group that is focused on translational/clinical applications of nanobodies. He currently is focusing on the development of nanobody-based immuno tracers as part of the IMI/EFPIA project entitled "Immune Image". Moreover, he is closely involved in multiple projects where he focuses on the generation of nanobodies against "difficult-to-target" proteins. In the near future, Timo hopes to combine his previous GPCR experience with his current focus to set up his own research line focusing on translational applications of GPCR-targeting nanobodies. Dr. Timo De Groof on the web LinkedIn Researchgate Twitter Medical Imaging Group Google Scholar Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

< Back to Webinars 📅 Tuesday, March 3, 2026 at 3:00:00 PM UTC 🤝 Webinar in collaboration with: Celtarys Research Fluorescent Probes for GLP-1R and GIPR Imaging: From Cell Assays to In Vivo Systems Fluorescent tools for imaging endogenous incretin receptors across biological systems Interrogating Incretin Receptor Biology Across Biological Complexity GLP-1 and GIP receptors have emerged as central targets in metabolic medicine, yet their precise localization, nanodomain organization, and functional engagement within complex biological systems remain incompletely understood. Fluorescent chemical probes offer one of the most direct approaches for investigating receptor distribution and dynamics in native contexts — without relying on receptor overexpression or genetic modification. This webinar introduces two families of advanced fluorescent probes developed specifically for working with endogenous GLP-1R and GIPR across a range of biological complexity. Attendees will gain a technical understanding of probe design, selectivity, and validated applications — as well as practical guidance on handling, reconstitution, dilution, and storage to support immediate laboratory deployment. LUXendin Family Red and far-red fluorescent GLP-1R antagonists derived from Exendin4(9–39). Enable high-specificity labeling of endogenous GLP-1R in live and fixed cells, pancreatic islets, and whole-organ preparations — without triggering receptor activation. Available across multiple spectral ranges for confocal, super-resolution, and intravital imaging. daLUXendin Family Fluorescent dual agonists for both GLP-1R and GIPR (daLUXendin544+ and daLUXendin660+), structurally related to tirzepatide. Enable simultaneous visualization of endogenous receptor localization and nanodomain organization in pancreatic islet cells and neural sites of action in vivo. Speakers Dr. Johannes Broichhagen Group Leader Leibniz Research Institute for Molecular Pharmacology (FMP), Berlin Dr. Broichhagen trained in chemistry at the University of Erlangen-Nuremberg, completed his doctorate at LMU Munich in 2014, and undertook postdoctoral work at EPFL (Switzerland) and the Max Planck Institute for Medical Research (Heidelberg). Since 2020, he leads an independent research group at the FMP Berlin. His group focuses on the development of chemical tools — including fluorescent ligands and photopharmacological compounds — to investigate GPCR biology with spatial and temporal precision. He is a principal architect of the LUXendin and daLUXendin probe families. Dr. David Hodson Robert Turner Professor of Diabetic Medicine Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford Dr. Hodson is a veterinary surgeon by training who pursued postdoctoral studies at the CNRS in Montpellier before establishing his independent laboratory at Imperial College London as a Diabetes UK RD Lawrence Fellow. He previously served as Professor of Cellular Metabolism and Institute Deputy Director at the University of Birmingham. His research group develops and applies novel technologies to investigate GLP-1 and GIP receptors — two class B GPCRs central to glucose homeostasis, food intake regulation, and inflammation — within complex tissue environments including the pancreas and brain. His work carries direct translational relevance to diabetes and obesity therapeutics. Organizers Celtarys Research Celtarys develops and commercializes fluorescent chemical tools and related screening services that enable fluorescence-based methods across drug discovery. The company's portfolio is built around high-affinity, selective fluorescent ligands for GPCRs, supporting researchers working at the interface of chemical biology and pharmacology. Broad GPCR fluorescent ligand portfolio across multiple receptor families Fluorescence Polarization, HTRF, and High-Content Screening formats Fluorescence microscopy and flow cytometry applications Screening services using proprietary probes in living cells Custom chemical development for probe and ligand creation Dr. GPCR Dr. GPCR is a membership-based nonprofit ecosystem dedicated to advancing GPCR-targeted drug discovery. It provides curated industry intelligence, expert-led masterclasses, and structured engagement opportunities for scientists and biotech leaders working across pharmacology, translational research, and therapeutic development. Curated intelligence on GPCR drug discovery trends and developments Expert-led webinars and masterclasses with leading researchers Structured networking for scientists and biotech professionals Nonprofit model — community-first, member-driven Free membership tier available Previous Webinar Next Webinar Don’t Miss the Next Live Session Dr. GPCR membership gives you access to all upcoming live, interactive webinars. Free. Takes less than a minute to join. Cancel anytime. Sign Up for Free

Bouvier on BRET, pharmacological chaperones, biased agonism, and why unexpected data is where real GPCR discovery begins. << Back to podcast list Strategic Partner(s) Michel Bouvier: BRET, Biased Agonism, and the Tools That Changed GPCR Pharmacology G-protein-coupled receptors were once described through a simple model: a lock waiting for a key. Agonists turned them on. Antagonists blocked them. The model was clean, teachable, and wrong in ways that took decades to prove. Michel Bouvier has spent his career building the tools to show why. From the development of BRET-based biosensors that revealed receptor behavior in living cells, to the discovery of pharmacological chaperones that rescue misfolded receptors from the endoplasmic reticulum, to the experimental frameworks that made biased agonism a credible drug discovery target - his lab has consistently produced technology before the field knew it needed it. This conversation covers the arc of that career: the personal loss that drew Bouvier toward the sympathetic nervous system, the postdoc in Bob Lefkowitz's lab during the molecular biology revolution in GPCR science, and the foundational question that has guided every receptor his lab has ever studied. Not which receptor - but which question. ABOUT THE GUEST Michel Bouvier is CEO of the Institut de Recherches Cliniques de Montreal (IRCM) and Principal Investigator at the Molecular Pharmacology Research Unit, as well as Professor in the Department of Biochemistry and Molecular Medicine at Universite de Montreal. He completed his PhD under Jacques de Champlain, studying the role of presynaptic adrenergic receptors in hypertension, and his postdoctoral training with Bob Lefkowitz at Duke University, where he was among the first scientists to achieve heterologous GPCR expression in mammalian cells alongside Brad Kobilka, Jeff Benovic, and others. His lab's contributions include the development of BRET (Bioluminescence Resonance Energy Transfer) technology for studying protein-protein interactions and receptor signaling in living cells, the pharmacological chaperone concept for rescuing misfolded GPCR mutants, and biosensor platforms that helped establish functional selectivity and biased agonism as drug discovery targets. SCIENTIFIC THEMES OF THE CONVERSATION The limits of the binary receptor model and what inverse agonism revealed BRET technology as a platform for studying GPCR signaling in living cells Pharmacological chaperones and the concept of rescuing misfolded receptors Functional selectivity and biased agonism as a framework for next-generation drug discovery How the tools available define the questions a lab can ask - and the questions that have to wait The personal and scientific roots of a question-driven research program KEY INSIGHTS FROM THE CONVERSATION The question comes before the receptor Bouvier has never chosen a receptor the way other labs do - as a system to commit to for a career. Every receptor his lab has studied was selected because it was the right model for a question that was already driving the program. That inversion - question first, receptor second - shaped a body of work that spans adrenergic receptors, chemokine receptors, vasopressin receptors, and class C GPCRs without ever being defined by any single one. Unexpected data is the signal, not the noise A line Bouvier returns to throughout his career, originally from Julie Axelrod via his PhD mentor Jacques de Champlain: when you get the data you expected, that's fine. When you get data you didn't expect and can rule out artifact - that's when you have something. This isn't just philosophy. It describes the actual origin of BRET, pharmacological chaperones, and the inverse agonism work - each born from a result that didn't fit the prevailing model. BRET was built in response to a rejection The technology that would become BRET emerged from a peer-review demand. A high-impact journal accepted the GPCR dimerization data but required evidence in living cells - which didn't exist yet and would take longer than the revision window to develop. Rather than wait, Bouvier's team submitted elsewhere and started building. The proximity assay that resulted, inspired by marine bioluminescence, became one of the most widely used tools in GPCR pharmacology. Pharmacological chaperones came from a project that looked dead A PhD student testing the effect of nephrogenic diabetes insipidus mutations on the V2 vasopressin receptor found that none of the mutants reached the plasma membrane. The project appeared finished. In the lab meeting that followed, someone suggested that a lipophilic antagonist might penetrate to the endoplasmic reticulum and stabilize a near-native conformation. Almost everyone dismissed the idea. Bouvier loved it. A call to Sanofi produced a compound from a drawer, the experiment worked, and the pharmacological chaperone concept was born. Inverse agonism split the room When Bouvier presented the concept of inverse agonism - compounds that inhibit the spontaneous activity of a constitutively active receptor - to a mixed audience of pharmacologists and chemists, the pharmacologists wanted to call it heresy. The chemists called it allosteric regulation and asked what was new. The divide illustrated something Bouvier has observed repeatedly: mental models, once useful, can become obstacles. The key-and-lock image that helped generations of students understand receptor pharmacology had calcified into a constraint on what the field was willing to see. Passion is not a soft variable Bouvier frames this explicitly and without sentimentality: research has periods where it is simply difficult, and passion is what carries a scientist through them. Not talent alone. He is careful to separate the two - invoking the Axelrod anecdote not to diminish intelligence but to make the case that sustained curiosity is the variable most trainable and most often underestimated by advisors and students alike. EPISODE TIMELINE Timestamps are AI-generated estimates based on transcript content. Verify against the final edited audio before publishing. 00:00 Introduction 02:23 Scientific origin - the high school chemistry teacher who made synthesis feel real 04:44 A father's death at 39 from hypertension and the path toward receptor pharmacology 08:18 Cold-calling Bob Lefkowitz - landing the postdoc that changed the trajectory 12:06 The meaning of unexpected data and what it signals about discovery 14:49 Arriving at Duke during the GPCR molecular biology revolution 17:50 Question-driven research - why Bouvier has never had a favorite receptor 20:03 The origin of BRET - dimerization controversy, marine bioluminescence, and a reviewer's demand 25:51 Building G-protein biosensors and the team that made it happen 27:57 From living-cell tools to drug discovery - baculovirus expression, inverse agonism, and biased agonism 34:15 Discovering pharmacological chaperones for V2 vasopressin receptor mutations 40:19 Advice for junior scientists and the rewards of discovery 43:41 Closing reflections SELECTED QUOTES "When you get a data that you did not expect and you rule out the possibility this is an artifact, well, now you have something. Now you have a real discovery, but you have to be smart enough to understand what it means and act accordingly." "We are not smart enough yet to understand exactly what it means, but let's work on it." "You're the first one seeing that. You're the first one understanding a little bit more how things work. And life is a lot about that." "The pharmacologists were ready to burn me for heresy, the chemists were saying, what's new, Pussycat? That's allosteric regulation." About Dr. Michel Bouvier Michel Bouvier is a professor of Biochemistry and Molecular Medicine and the CEO of the Institute for Research in Immunology and Cancer ( IRIC ) at the Université de Montréal. Following his Ph.D. in Neurological Sciences at the same university in 1985, he completed a post-doctoral fellow at Duke University in the laboratory of Robert Lefkowitz. In 1989, he returned to Montréal as a professor of biochemistry and a scholar of the Medical Research Council of Canada at the Faculty of Medicine of the Université de Montréal. Since 2001, he holds the Canada Research Chair in Signal Transduction and Molecular Pharmacology. Dr. Bouvier is the author of 300 scientific papers and 15 patents and delivered close to 500 invited conferences. He is a world-renowned expert in the field of cell signaling and GPCRs and made seminal contributions to our understanding of this major class of drug targets. In addition to paradigm shifts including inverse agonism, biased signaling, and pharmacological chaperones, his work on bioluminescence resonance energy transfer (BRET) resulted in the development of screening assays that are now widely used for drug discovery. His work received more than 30,000 citations yielding an h-index of 95. He has supervised the research work of 75 graduate students and 40 post-doctoral fellows. Michel’s scientific contributions were recognized by the attribution of many awards and distinctions including his election as a fellow of the Royal Society of Canada (2014), the Julie Axelrod award from the American Society of Pharmacology and Exerimental Therapeutics (2017), the Wilder Penfield award from the Quebec Government (2017), the innovation award of ADRIQ (2019) and the 2021 Killam prize form the Canada Council for the Arts. As some of you may know, Michel was one of my professors at the Universite de Montreal. He was also the head of both my Master’s and Ph.D. thesis committees. I was and am still impressed by Dr. Bouvier’s ability to ask highly relevant questions during meetings. In this episode, you will hear us talk about it. I spent some time working in Michel’s lab with some of his postdocs and although I was never officially a member of the lab, I am humbled to have been able to work with him and his team and use the tools developed in his lab to better understand GPCR structure/function relationships. Dr. Michel Bouvier on the web Wikipedia IRIC Bouvier Lab Google Scholar Pubmed ResearchGate Twitter LinkedIn Universite de Montreal- Department of Biochemistry and Molecular Medicine Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Founded in 2020, Dr. GPCR unites researchers, industry, and partners to accelerate GPCR science and drug discovery—through connection, education, and real‑world collaboration. About Dr. GPCR Ecosystem We unite the GPCR community to advance drug discovery. We bring the GPCR community together to fuel GPCR drug discovery—one receptor at a time. Our goal is to deepen our understanding of GPCR function and accelerate the development of better therapies together. Founded in 2020, Dr. GPCR was created to break down barriers across academia, biotech, pharma, and CROs—so knowledge, tools, and talent can flow where they’re needed most. Contact Us Our Mission Advance GPCR science and drug discovery by connecting people, data, and opportunities across the global GPCR ecosystem. Our Vision A world where GPCR insights translate quickly into real‑world therapies through an open, trusted, and collaborative community. What We Do (in Three Verbs) Connect — Researchers, founders, students, and industry partners meet, learn, and collaborate. Educate — Courses, talks, and curated content that turn expertise into execution. Accelerate — Intros, resources, and visibility that move projects and careers forward. Who Should Join To join the community, you should be actively related to the GPCR field , including: Academic researchers (PI, postdoc, student) Industry scientists and R&D leaders Biotech and pharma founders/operators CRO/technology providers serving GPCR programs Clinicians and translational teams Investors and BD professionals focused on GPCRs Eligibility: We verify GPCR relevance during onboarding to preserve focus and quality. Partner With Us Build visibility, trust, and feedback directly from your target audience. Partner perks: Direct interaction with researchers, founders, and decision‑makers Access to all member perks for your entire team Product & service listings in ecosystem directories Speaking, demo, and content opportunities Input into community programming and field priorities CTA: Contact us to partner Our Values Scientific Rigor — Evidence first; hype last Openness with Intent — Share to accelerate; respect boundaries Diversity & Inclusion — More perspectives → better science Member‑First — We build what the community needs Execution — Ideas become results through consistent cadence Meet The Team Founder & Director Yamina Berchiche Get in touch Co-Founder Attila Foris Get in touch Board Member Anne M. Quinn Get in touch Board Member JoAnn Trejo Get in touch Board Member Maria Waldhoer Get in touch Chief Matchmaker Mark Schmeizl Get in touch

Join us as a featured guest on the Dr. GPCR Podcast! Explore the fascinating career journeys, groundbreaking discoveries, and impactful contributions of experts in GPCR biology. Share your insights and be part of the conversation. Complete the form below to become a guest - we'll reach out within 48 hours. Don't miss this opportunity to showcase your expertise! Be Our Guest – Dr. GPCR Podcast Share Your Research. Inspire the GPCR Community. Every episode of the Dr. GPCR Podcast features leading scientists, innovators, and biotech professionals whose work is advancing the understanding of G Protein-Coupled Receptors (GPCRs). We discuss breakthrough discoveries, career paths in pharmacology and molecular biology, and how each guest’s research contributes to the global GPCR ecosystem. If you’re working on exciting GPCR-related research — from structural biology to drug discovery — we’d love to feature your story. Fill out the form below and our team will contact you within 48 hours. Fill out this form Frequently asked questions About the Dr.GPCR Podcast At the high of the pandemic, I created the Dr. GPCR Podcast with three major goals in mind: Share the latest scientific discoveries in the GPCR field through discussions with experts Provide researchers with a different outlet to make their work known and Inspire young scientists to work on GPCRs It’s been a privilege to chat with so many GPCR scientists since 2020. Dr. GPCR’s mission is to bring together the GPCR community from all corners of the world to connect, exchange, and collaborate to improve human health through a better understanding of GPCR biology. So far we have recorded and released over 156 episodes and hosted GPCR specialists from all over the world, includingDr. Bryan Roth, Dr. Robert Lefkowitz, Dr. Fiona Marshall, Dr. Sam Hoare, Dr. Graciela Pineyro, Dr. Debbie Hay, Dr. Randy Hall, tributes toDr. Marc Caronwith over 30 guests includingDr. Kathleen Caron, Dr. Brian Kobilka, and many other amazing scientists. What is the format of the Dr.GPCR Podcast? Our podcast typically follows an interview-style format. We aim to have engaging conversations about you as a scientist, your career, your work, and anything related to GPCRs to provide valuable insights for our listeners. How long will the podcast recording take? The duration of the podcast recording may vary depending on the episode's topic and the flow of the conversation. On average, recordings usually take around 1 hour. We strive to keep the conversation focused and efficient while allowing enough time for in-depth discussions. How do I book the meeting on Calendly? In the invitation we provided a booking link. When clicking the link you’ll see a calendar, pick any date, and the schedule options will pop up. Then you will be asked to leave your name and email for future automated messages around our meeting. Can I reschedule or cancel our meeting? Yes, you can reschedule or cancel our meeting through Calendly. What should I expect during the recording process? Before we hit record, we will have a few minutes to discuss any questions or concerns and give you time to get comfortable. During the recording process, we will begin by introducing the episode and presenting you as our guest. We'll then engage in a conversation centered around your career and how you got introduced to GPCRs. Feel free to share your thoughts, experiences, and insights openly. If there are specific questions or talking points we plan to cover, we'll provide them in advance to help you prepare. We aim to ensure you have a great time and give a sneak peek at who you are as a scientist to the GPCR community. How should I prepare for the podcast recording? We always send our guests a Podcast Episode Outline, which includes all the questions we typically ask during the recording. You can take some time to gather your thoughts around these key points. These questions just serve as a guide, and we don’t have to go through all of them. Think of our chat as a casual discussion at an in-person conference where we are meeting for the first time. Sometimes we don’t follow the questions outlined because the discussion takes us to an also relevant and interesting conversation. We want to make sure that you are comfortable and we will never ask questions that would make you uncomfortable. Do I need to bring any equipment for the recording? In most cases, you won't need to bring any equipment for the recording as computers usually have all the necessary equipment integrated. If you do have an external microphone or webcam you’d like to use, it will make a difference, just make sure they are connected and working properly before going into the meeting. How do I join the recording session? All recordings are conducted via Zoom. Please ensure you test your Zoom setup before the meeting to avoid any technical issues. Are there any features you’d recommend to use? Recordings are done on Zoom. Touch-up- my appearance. Adjust for low light. We encourage you to have a headset with a good microphone. We also encourage you to be sitting in front of a window or in front of a sort of light so that your entire face can be seen in the recording. Please note that we do record audio and video. Can I promote my work or projects during the podcast? Absolutely! We encourage our guests to share information about their work, projects, or any relevant initiatives they are involved in. Our podcast is a great platform for you to showcase your expertise and connect with the GPCR community. Please feel free to mention and discuss your work during the conversation. Will there be an opportunity for me to ask questions or clarify any points? Yes, we value the interactive nature of our podcast and welcome your questions or requests for clarification. If you'd like to ask anything or any points you'd like to clarify before, during, or after the recording, please don't hesitate to speak up. We want to ensure that the discussion is engaging and informative for both our guests and our community. How will the podcast episode be promoted? Once the episode is recorded and edited*, we will promote it through various channels, including our website, multiple podcast streaming platforms, social media platforms, and email newsletters. We encourage you to share the episode with your audience as well. Together, we can maximize the episode's reach and impact. *Note that by editing, we mean removing any interruptions, or background noises, from the recording. We will not edit what you say unless you ask us to remove or add sections, sometimes we can re-record. When can I expect my podcast episode to be released? Your podcast episode will be released based on our production schedule and the order of episodes in the queue. We aim to provide an estimated release date after recording. Typically, episodes are released 4-6 weeks after recording. We'll notify you once it's live so you can share it with your network. Note that this timeline may vary if we take a break from releasing episodes, usually between December 15 and January 15. Can I listen to the episode after it’s been recorded? If you would like to listen to the episode after being recorded, we are more than happy to send it to you for your review. That being said, if there’s anything you’d like us to edit, feel free to reach out so we can work on it before it gets published. Can I watch the video podcast after it’s been published? The podcast video recordings are only available for the Premium Members on our Ecosystem. Anyone with a Free website membership or with an account on the different streaming platforms will have access to the podcast version only. How can I stay updated on future episodes or collaborate again in the future? To stay updated on future episodes and potential collaboration opportunities, we recommend subscribing to our podcast on your preferred platform. If you are interested in collaborating again, you can always fill out this form again and/or write to any of the following emails: hello@drgpcr.com I am still an undergraduate, Ph.D. student, or a post-doc, am I welcome to join as a guest? Yes, we value what anyone in the GPCR field has to say. For Dr.GPCR you are an expert in your own project, and we highly encourage you to accept our invitation to participate in the Podcast. Don’t hesitate to reach out to us if you’d like to recommend a colleague as a guest. Do you have any suggestions in terms of podcast equipment? Yes, here’s a list of accessible items we recommend for podcast creators: Video conference Lighting Kit Wireless microphone Any tips on achieving good lighting for the video podcast recording? Good lighting is key for any type of video. Here are some easy tips: Sitting in front of a window is always the best option for good lighting on any type of video. If we are recording at night or you don’t have natural light in your usual space, you can always use a desk lamp and put it next to the computer. The front light is always more flattering than the top light, which is what we usually have in house spaces. If you want to go like a pro, you can turn on a front light, and a backlight, that way you won’t look plain on camera. Listen and subscribe where you get your podcasts

Discover how GPR65 reshapes our understanding of GPCR signaling and its role in cancer, with Dr. Ian Chronis on the Dr. GPCR podcast. << Back to podcast list Strategic Partner(s) Signals, pH, and Discovery : Cracking GPCR Mysteries with Dr. Ian Chronis In this episode, we welcome Dr. Ian Chronis, a recent Ph.D. graduate preparing to begin his postdoctoral work at the University of Michigan. Host Yamina Berchiche sets a welcoming tone as they dive into Ian’s unique academic journey—from early interests in medicine to his pivot toward pharmacology and GPCR research. His story offers valuable insights for anyone navigating the path from student to scientist. Ian discusses how his experiences at the University of Chicago and the University of Michigan shaped his scientific curiosity, particularly around G protein-coupled receptors (GPCRs) . His research centers on the beta-2 adrenergic receptor and GPR65 , a proton-sensing receptor with promising implications in cancer biology. He shares fascinating findings from his work on GPR65 , highlighting its unusual constitutive internalization and its ability to signal from acidic endosomes. This dual functionality—environmental sensing and compartment-specific signaling—offers a new layer of complexity in GPCR behavior. Yamina underscores the therapeutic potential of GPR65, especially in the context of cancer immunotherapy, and how understanding receptor activity in acidic micro environments could unlock new therapeutic strategies. Throughout the episode, Ian reflects on the value of a supportive lab culture , the need for better experimental tools in GPCR signaling , and the importance of engaging with the broader GPCR research community to drive innovation. The conversation wraps with a playful exchange about possible podcast titles, with Yamina suggesting "Ancient Greek Chemistry and GPCRs"—a nod to Ian’s heritage and the wide-ranging themes covered. This episode is both educational and inspiring, offering a behind-the-scenes look at a rising scientist’s journey in the ever-evolving world of GPCR research. About Ian Chronis I recently finished my PhD in the lab of Dr. Manoj Puthenveedu at the University of Michigan, where I am now working as a postdoc. My research has looked at the trafficking and signaling of adrenergic and proton-sensing receptors, with specific focus on identifying novel regulatory proteins governing their function. Ian Chronis on the web LinkedIn Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< 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 Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Bianca Plouffe About Dr. Bianca Plouffe Dr. Bianca Plouffe obtained her B.Sc. in Biochemistry in 2003 from Université de Sherbrooke (Qc, Canada). She then completed an M.Sc. in Physiology from the same university in 2005 by investigating the molecular mechanisms involved in the angiotensin type 2 receptor (AT2R)-mediated neurite outgrowth while characterizing new selective AT2R agonists. In 2006, Bianca obtained a Doctoral Scholarship from the Fonds de Recherche du Québec en Santé. She moved to the University of Ottawa to complete a Ph.D. in Neuroscience. She identified the molecular mechanisms involved in the opposite regulation of dopamine D1 and D5 receptors by protein kinase C. After obtaining a Postdoctoral Fellowship from the Canadian Institutes of Health Research in 2012, Bianca joined the research group of Prof Michel Bouvier at Université de Montréal. As part of Bouvier’s team, Bianca used Bioluminescence Resonance Energy Transfer (BRET)-based technology to tackle important questions related to GPCRs. She identified the structural determinant controlling biased signaling of melatonin type 2 receptors in the context of protection against type 2 diabetes. Bianca also collaborated with Prof. Robert Lefkowitz , which led to the finding that both β-arrestin and G protein can simultaneously bind to some GPCRs when signaling in endosomes by forming a megaplex. In 2018, Bianca was appointed Vice-Chancellor’s Fellow at Queen’s University Belfast to develop her research program. Funded by a Wellcome Trust Seed Award, she investigated biased and compartmentalized G protein signaling by the vasopressin type 2 receptor. In 2021, Bianca secured a permanent position as a lecturer. Her subsequent work has focused on understanding the role of compartmentalized Gq signaling by the cytomegalovirus-encoded chemokine US28 receptor in the context of glioblastoma. Dr. Bianca Plouffe on the web Queen's University Belfast website LinkedIn ResearchGate ORCID Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Dr. Foord reflects on discovering RAMPs, deorphanizing GPCRs, and navigating industrial GPCR pharmacology, target validation, and drug discovery strategy. << Back to podcast list Strategic Partner(s) Foord: Serendipity, RAMPs, And Industrial GPCR Pharmacology Scientific Abstract This conversation traces how GPCR pharmacology, receptor signaling, and drug discovery evolved inside one of the world’s largest pharmaceutical organizations. Dr. Foord reflects on his path from academic neuroendocrinology to introducing molecular biology and molecular pharmacology into Glaxo’s GPCR programs, and on the combination of rigor, bioinformatics, and serendipity that led to several influential discoveries. He describes the purification and cloning of the CGRP receptor, the identification of receptor activity-modifying proteins (RAMPs), and the realization that CGRP signaling required receptor complexes rather than a single seven-transmembrane protein, reshaping thinking about peptide receptor activation and ligand binding. Dr. Foord also discusses work on angiotensin, GABA B, free fatty acid, nicotinic acid, and prostaglandin EP4 receptors, showing how orphan receptors were deorphanized using expression systems, electrophysiology in Xenopus oocytes, and early bioinformatics. The discussion highlights the gap between identifying a target and delivering a drug, the challenges of target validation, and the realities of industrial decision-making around receptor selectivity, safety, and market focus. Along the way, Dr. Foord reflects on the limits and promise of human genetics, the underexploited potential of GPCR antibodies, and the importance of team composition, negative data, and scientific community in navigating complex receptor biology. About the Guest Dr. Foord is a physiologist and pharmacologist who spent more than two decades at Glaxo, Glaxo Wellcome, and GlaxoSmithKline working on GPCR pharmacology and drug discovery. Trained in neuroendocrinology, he helped bring molecular biology into traditionally pharmacology-driven GPCR programs and worked across migraine, cardiovascular, pain, and inflammation projects. His work contributed to the identification of RAMPs in the CGRP receptor system, deorphanization of several GPCRs including GABA B and carboxylic acid receptors, and discovery of a prostaglandin EP4 modulator that advanced as a drug candidate. Later in his career, Dr. Foord led bioinformatics for neuroscience and played a central role in GSK’s early large-scale genetics initiative, integrating GPCR targets, ion channels, transporters, and ligands into association studies. His experience spans receptor cloning, expression systems such as Xenopus oocytes, electrophysiology, molecular pharmacology, and the use of informatics to mine sequence, structural, and genetic data for new receptor targets. Key Insights from the Conversation RAMPs Reframed Peptide GPCR Pharmacology . Dr. Foord explains how attempts to clone the CGRP receptor from SK-N-MC cells, combined with highly sensitive cAMP readouts in Xenopus oocytes, unexpectedly pulled out RAMP1 rather than a conventional seven-transmembrane receptor. The realization that RAMPs co-assemble with CRLR to form CGRP and related receptors forced a reconceptualization of peptide receptor activation and made clear that receptor complexes, not single proteins, could underlie pharmacological specificity. Serendipity Depends on Experimental Design and System Choice . The discovery of RAMPs was only possible because the assay tied receptor signaling to a highly amplified electrophysiological readout, revealing dramatic effects that might have been lost in noisier systems. Similarly, placental tissue became the source for CGRP receptor purification simply because binding studies showed it combined high receptor density with practical availability, illustrating how pragmatic choices in model systems can open unexpected paths in GPCR pharmacology. Deorphanizing Receptors Blends Bioinformatics and Bench Work . Dr. Foord describes a period where his group repeatedly identified ligands for orphan receptors: the second GABA B subunit via yeast two-hybrid, a carboxylic acid receptor when the solvent turned out to be the real agonist, and a nicotinic acid receptor by intersecting tissue expression data with orphan GPCRs. These stories show how careful pharmacology, informed sequence analysis, and attention to apparent artifacts can reveal new receptor signaling pathways relevant for metabolism and cardiovascular disease. Target Validation Is Harder Than Cloning a Receptor . From the non-existent second AT1 angiotensin receptor to the MAS oncogene as a poor angiotensin responder, Dr. Foord emphasizes how easy it is to be misled by overexpressed systems and noisy orphan receptor data. Southern blotting, cross-hybridization, and later genetic analyses ultimately showed that some hypothesized subtypes were artifacts, underscoring that robust target validation is a distinct and often more challenging problem than receptor cloning or initial ligand binding assays. Drug Discovery Is Constrained by Selectivity, Safety, and Strategy . The CGRP story illustrates how structural biology and pharmacology intersect with corporate decisions: once it became clear that the CRLR binding pocket is shared across CGRP, amylin, and adrenomedullin receptors, small-molecule selectivity looked problematic. Later hepatotoxicity concerns and the success of antibody therapeutics further shifted strategy. Similar strategic considerations shaped the fate of the EP4 partial agonist that ultimately found a niche in veterinary medicine rather than human rheumatoid arthritis. Genetics and Informatics Offer Power but Not Simple Answers . As Head of Bioinformatics for Neuroscience, Dr. Foord participated in GSK’s early large-scale association genetics effort, feeding GPCRs, ion channels, and transporters into case–control studies. Apart from APOE4 in Alzheimer’s disease, most signals failed to reach robustness with available cohort sizes, tempering expectations that genetics alone would deliver pipelines of GPCR targets. He argues that integrating structural biology, computational pharmacology, and genetics may still be key to understanding receptor activation in patients, but requires realistic views of effect sizes and trial design. Scientific Careers Depend on Teams, Mentors, and Community . Reflecting on his path from physiology to molecular pharmacology to bioinformatics, Dr. Foord highlights how good mentors, diverse teams, and open sharing of reagents and ideas enabled progress. He stresses the value of lab “optimists and cynics,” the importance of talking about negative results, and the role of informal networks in preventing wasted effort. For younger scientists, his advice centers on doing work you genuinely enjoy, finding supervisors who connect you to the broader GPCR community, and being willing to pivot as new methods and questions emerge. Episode Timeline 00:00 — Early academic work in neuroendocrinology, self-experimentation with TRH and somatostatin, and first encounters with hormones and GPCRs. 02:00 — Move to Roger Craig’s lab, purification of the CGRP receptor from human placenta, and practical considerations in choosing receptor-rich tissues. 05:00 — Transition from academia to Glaxo, early HIV TAT work in Xenopus oocytes, and the emergence of molecular pharmacology within a pharmacology-led organization. 10:30 — Expression cloning of the CGRP system, discovery of RAMP1, and how oocyte electrophysiology revealed a massive potentiation of endogenous CRLR signaling. 18:00 — Industrial migraine programs, small-molecule CGRP antagonists, challenges with selectivity and liver toxicity, and the later success of CGRP antibodies. 20:00 — Angiotensin receptor work, using Southern blots to hunt for a non-existent AT1 subtype, and the MAS oncogene as a cautionary tale in receptor signaling artifacts. 30:00 — Discovery of the prostaglandin EP4 receptor while searching for angiotensin-related sequences, development of an EP4 partial agonist, and its path into veterinary medicine. 34:00 — GABA B receptor complex, identification of the second subunit via yeast two-hybrid, and closing the chapter on proposed additional GABA B subtypes. 39:00 — Large-scale genetics and bioinformatics at GSK, expectations for GPCR target discovery from association studies, and reflections on why many signals remained elusive. 52:00 — Career advice on doing work you enjoy, the importance of mentors and connectedness, and how team composition and negative data shape GPCR research and drug discovery. Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

A conversation with Dr. Silvio Gutkind on keeping a cancer research lab running at 10% occupancy, why rotation students act like a sorting hat, and why breakthroughs come from working hypotheses that fail. << Back to podcast list Strategic Partner(s) Silvio Gutkind: Building a Lab That Doesn't Shut Down Conversations that happen when a research community faces a shared constraint reveal as much about scientific practice as any experiment. Dr. Silvio Gutkind joins this resilience conversation from the UCSD Moores Cancer Center, where cancer patients cannot wait for normalcy to return. For Dr. Gutkind — carrying a personal loss in New York and leading a cancer center building that operated at 93% capacity during the early pandemic — the question was not abstract. He had to decide, week by week, what could pause and what couldn't, and whose careers would bear the cost of getting it wrong. He walks through the structure his team built: staggered schedules at 10–15% occupancy, written contracts with every lab member, a Zoom-based communication cadence, and an internal directive to read, think, plan, and write. The constraint did not slow the science; it redirected it. Bioinformatics projects flourished. Collaborations that would have waited for conferences started immediately. A harder question surfaces underneath: how much of what we call a lab is its physical walls, and how much is the community, the plan, and the willingness to let a failed hypothesis open a new direction? About the Guest Dr. Silvio Gutkind is Professor and Associate Director for Basic Science at the UCSD Moores Cancer Center. His research spans GPCR signaling in cancer biology, head and neck squamous cell carcinoma, and the molecular circuitry that drives tumor progression. Before moving to La Jolla, he spent decades at the NIH, where he led a branch at NIDCR. That dual lineage — extramural academic and intramural NIH — shapes how he thinks about research infrastructure, student training, and scientific community. Scientific Themes of the Conversation Institutional resilience and the architecture of a research lab under constraint The contract between scientific leadership and trainees during crisis Communication infrastructure as a substitute for physical proximity Chance and opportunity as drivers of a scientific career Rotation students as cross-pollinators between labs Why breakthroughs tend to come from working hypotheses that fail Key Insights from the Conversation Cancer centers don't get to pause. Dr. Gutkind describes operating his cancer research building at 93–94% capacity during the early pandemic because cancer patients couldn't wait for normalcy. The question was never whether to stay open — it was how to stay open safely, and how to absorb the stress that came with that responsibility. The NIH shutdown playbook made UCSD ready. Years at the NIH, where federal shutdowns were routine, gave Dr. Gutkind a pre-built mental model for what to freeze, what to protect, and what to let continue. When the pandemic hit, he reached for an infrastructure he already had. Every lab member needed a contract. Rather than making ad hoc decisions about who would come in and when, the team wrote down expectations — hours, distancing, critical versus deferrable work, and an explicit clause that no one should feel pressured to be on-site. The contract wasn't bureaucracy; it was protection, especially for students. The bioinformatics arm called it "heaven." Computational scientists suddenly had uninterrupted time at home with full data access and far fewer meetings. Dr. Gutkind reports that five years' worth of ideas accumulated in that stretch — more than the lab can realistically work through. "Physical distancing," not "social distancing." A small language correction with structural weight. Dr. Gutkind argues the scientific community grew closer during the pandemic, not further apart — the physical space contracted, but the community expanded through Zoom, shared drives, and unhurried collaboration conversations. Rotation students function like the sorting hat. Because trainees rotate through multiple labs, they carry science from one bench to another. Dr. Gutkind credits several of his most valuable collaborations to a rotation student recognizing a fit that no PI would have spotted from across campus. Breakthroughs come from working hypotheses that fail. Dr. Gutkind reflects that the most significant advances in his career didn't come from confirming a premise — they came from digging into why the premise broke. The discipline is not in being right, but in being willing to let go of the framework you built when the data refuses to fit it. Episode Timeline Timestamps were generated using AI for readability. 00:00 Welcome and introduction 01:46 Navigating research during the pandemic 03:30 Why cancer research couldn't stop 04:30 The NIH shutdown playbook 05:20 Writing the contract: occupancy, staggering, communication 06:50 The productivity paradox — "it's like heaven" 07:55 What will change after the pandemic 09:20 "Physical distancing, not social distancing" 11:31 Chance versus scientific knowledge in a career 12:20 Rotation students as the sorting hat 13:20 When the working hypothesis fails 14:30 Closing Selected Quotes "We have many more ideas than we can handle for at least the next five years." "I wouldn't call it social distancing — I would call physical distancing… as a community, we are even stronger." "These rotation students are like cross-pollination… almost like the sorting hat in Harry Potter." "Quite often, our breakthroughs are more often from when the working hypothesis did not work. The breakthrough came from getting deeper into why." About this episode Dr. J. Silvio Gutkind sheds light on his work and life since the beginning of COVID restrictions. A large component of his work is centered around dysregulated signaling in cancer and the development of novel mechanism-based cancer therapies. In this episode, Dr. J. Silvio Gutkind highlights how his past experience proves useful in current COVID times and potential benefits the changes in work environments can do for future collaborations. Dr. J. Silvio Gutkind on the web Gutkind Lab – UC San Diego Moores Cancer Center Gutkind Lab publications More Publications from the Gutkind Lab on Pubmed Dr. J Silvio Gutkind on LinkedIn Gutkind Lab on Twitter UCSD Moores Cancer Center Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Five scientists audit what AI can and can't do for GPCR drug discovery — from orphan receptors and biased signaling to the true-negatives problem nobody writes into grant proposals. Recorded at the 3rd EARNEST meeting. << Back to podcast list Strategic Partner(s) EARNEST Panel: Can AI Accelerate GPCR Drug Discovery? In October 2020, five scientists gathered virtually at the 3rd EARNEST meeting to debate a question that has only grown more urgent: can artificial intelligence actually accelerate GPCR drug discovery, or is it mostly a rebranding of methods the field has used for decades? Panelists from InterAx Biotech, Rockefeller University, and the University of New Mexico — computational chemists, systems biologists, structural biologists, and drug-discovery veterans — drew on their combined experience to separate what machine learning can credibly do for GPCR research from what still depends on pharmacological judgment. The conversation moves from definitional clarity (AI is not machine learning, and neither is simple computational modeling) to the practical realities of building usable datasets, deorphanizing receptors, handling generative models, and confronting the true-negatives problem that quietly breaks so many published models. For any scientist whose grant proposal now contains the phrase "machine learning" whether they fully believe in it or not, this panel is an honest audit of what the technology can deliver today and where it still falls short. About the Panelists Dr. Maria Waldhoer is Chief Scientific Officer at InterAx Biotech in Switzerland. A pharmacologist by training, she spent more than six years in early R&D at Novo Nordisk before turning to systems biology approaches for connecting in vitro signaling data to in vivo drug behavior. Dr. Aurélien Rizk is Chief Technology Officer at InterAx Biotech. Trained as a mathematician and computer scientist, his doctoral work focused on developing new methods for modeling GPCR signaling pathways. Dr. Yaroslav Nikolaev is a scientist at InterAx Biotech with a dual background in biology and computation. His research combines biomolecular NMR, structural biology, and machine learning to study how GPCRs function dynamically. Dr. Thomas Sakmar has run a laboratory at Rockefeller University for roughly thirty years. His group contributed to the early cloning of GPCRs in the mid-1980s and has since pushed the boundaries of GPCR biochemistry — including early homology modeling, coarse-grained molecular dynamics, and genetic code expansion for site-specific chemistry on receptors. Dr. Tudor Oprea is Principal Investigator at the University of New Mexico and coordinator of the Illuminating the Druggable Genome Knowledge Management Center. An MD-PhD who has practiced machine learning since 1989, he built Pharos, the public-facing data platform for the IDG program, and co-developed G1, the first agonist for GPR30, which reached an IND for melanoma. Scientific Themes of the Conversation The definitional boundary between AI, machine learning, and computational modeling Data quality as the rate-limiting step for machine learning in GPCR pharmacology Orphan receptor deorphanization and the limits of learning from known peptides Generative models, scoring functions, and the role of molecular dynamics in ligand design The true-negatives problem and how it distorts biological models The hybrid future: chemical intuition, experimental judgment, and where computation still falls short Key Insights from the Conversation AI and machine learning are not the same thing, and the difference matters. Machine learning finds patterns in defined datasets; AI aims to substitute for human reasoning more broadly. Using the terms interchangeably blurs what each approach can realistically deliver in a pharmacology workflow. The barrier isn't messy data — it's missing metadata. Most pharmacology datasets aren't useless for ML; they're incomplete. Buffers, incubation temperatures, time points, co-expression conditions, the specific Emax reference — these are the details that determine whether a dataset can be pooled with others or must stand alone. Deorphanization via AI is possible, but constrained by what we already know. Random-forest classifiers trained on known peptide ligands can find new orphan-receptor pairings. But the remaining orphans may be orphans precisely because they don't resemble anything we've characterized — which caps what this class of model can find. The bottleneck in structure-guided ML isn't the algorithm. The panel agreed that the real limits are the availability of high-resolution GPCR structures and the computational cost of molecular dynamics simulations needed to capture the dynamic conformations behind signaling. True negatives quietly wreck biological models. Most published models rely on inferred negatives — genes or molecules assumed inactive by convenience. When one panelist replaced inferred negatives in an autophagy model with CRISPR-validated true negatives, the model's predictions changed radically. Chemical intuition has no AI equivalent yet — and won't soon. The experience of a seasoned medicinal chemist mentally docking a molecule from a 2D structure is not a skill current models replicate. The panel expects a hybrid future, not a replacement one, for the next five to ten years. Olfactory GPCRs remain a trillion-dollar opportunity the field has largely ignored. GPCR-targeting drugs represent roughly 0.9 trillion dollars in global sales across 75 countries. Olfactory GPCRs — which account for a large fraction of the receptor class — have been systematically sidestepped for lack of tractable in vitro screening methods. Episode Timeline 00:00 Welcome from Yamina Berchiche 01:36 Panelist introductions 11:41 AI vs machine learning — the definitions that matter 15:21 The undrugged majority: 400 non-olfactory GPCRs, only 160 drugged 20:12 What makes a pharmacology dataset usable for machine learning 24:41 Advice for small academic labs entering the field 30:34 Can AI help deorphanize understudied receptors? 37:01 Reading GPCR signaling dynamics with computational models 39:53 Generative models, scoring functions, and molecular dynamics 50:32 The true-negatives problem and the limits of inferred datasets 52:30 Hype vs reality in AI drug discovery 55:05 Where the GPCR field goes in the next five years Timestamps were generated using AI for readability. Selected Quotes "My computational team told me, 'this receptor is not using arrestin to internalize. There has to be an arrestin-independent thing there.' And I'm like, that's rubbish. Never picked it up. Complete rubbish. And then a year later or so, I get a call from a colleague who said, 'oh, we've tested this compound as a negative control because we thought it doesn't need arrestin to internalize. And now we put it in this CRISPR knockout cell and — it does.'" — Dr. Maria Waldhoer "In 1989, as a med student in Romania, I used BASIC to model the variation in heart rate and blood pressure for 11 patients. I wrote an 11 polynomial that fit everything, so I thought I had solved the problem with drug discovery. I have learned a lot since." — Dr. Tudor Oprea "Dan Rich worked on HIV protease inhibitors. He would look at the 2D structure and basically mentally do a docking and tell you whether that's a good protease inhibitor or not. I think there are people who have worked in the GPCR field that can do a similar exercise." — Dr. Tudor Oprea "If you only make big enough numbers, big enough networks, big enough algorithms, suddenly intelligence pops out on the other side. [Roger Penrose] said, well, it's simply because they cannot think of anything else to do yet." — Dr. Maria Waldhoer About this episode Listen to this fantastic round table discussion that I had the privilege to moderate with Alexander Hauser . Our guests were Maria Waldhoer , Tudor I. Oprea , Thomas Sakmar , Aurelien Rizk & Yaroslav Nikolaev . The explosion of biomedical data such as in genomics, structural biology, and pharmacology can provide new opportunities to improve our understanding of human physiology and disease. In recent years, machine learning (ML) and artificial intelligence (AI) methods have received a significant boost in attention. ML/AI can be powerful for identifying abstract patterns within large data where traditional methods would be oblivious to. This comes without the need for manual feature engineering as systems can learn through implicit rules from the data provided. G protein-coupled receptors (GPCRs) mediate a vast variety of critical biological processes and provide an ideal case study for quantitative, and multi‐scale integration of these amounts of data to gain novel insights into receptor biology. How can we best leverage these exciting new techniques in areas such as protein structure prediction, bioactive ligand discovery, in-vivo translation ability, or in our understanding of signaling determinants? Here, we would like to discuss the opportunities, weaknesses, and advantages of these new technologies, which may contribute to probe our favorite targets at all scales. For more information on the ERNEST network, visit https://ernest-gpcr.eu/ . Dr. Yamina Berchiche on the web Website LinkedIn Publications Twitter Facebook Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

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Sokhom Pin shares how he built a biotech career around GPCRs, designed a custom PhD path, and led teams through empowerment and purpose. << Back to podcast list Strategic Partner(s) GPCR Pharmacology, Career Twists & Serendipity with Sokhom Pin From the Bench to the Boardroom Sokhom Pin’s story begins not with prestige or privilege but with grit and commitment. From his early work as a technician at Johns Hopkins Hospital to leading biology at Servo Therapeutics, Sokhom’s journey is rooted in practicality and purpose. He shares: "All my industry experience has been GPCR-focused." Starting at DuPont, then BMS, Novartis, and eventually founding in vitro pharmacology departments, Sokhom always stayed anchored to G protein-coupled receptors (GPCRs). Family First, Always The decision to shift from academia to industry wasn’t driven by disillusionment—it was about responsibility. “I had two kids and realized I just couldn’t support a family on a technician’s salary.” This pragmatic decision led him to high-throughput screening at DuPont, proving that scientific ambition doesn’t have to mean sacrificing personal commitments. Falling in Love with GPCRs GPCR pharmacology captured his scientific curiosity. Sokhom recalls how binding assays at BMS introduced him to the depth and complexity of receptor pharmacology: “It’s not just about IC50s. There’s allosterism, receptor desensitization… it opened a whole new world.” This moment became pivotal—transforming technical proficiency into passion. Designing a Non-Traditional PhD While working full-time, Sokhom architected a one-of-a-kind PhD program between BMS and UConn. “I had to find a way. I wanted a PhD, but I couldn’t quit my job.” Through strategic coordination, he executed a PhD entirely in the industry setting—efficient, targeted, and rooted in real-world projects like CGRP receptor antagonists. From Scientist to Leader At Alkermes, Sokhom took his first leadership role and finally experienced the power of empowerment . “That’s the moment that changed my entire career. I was trusted to build a team from scratch.” He focused on culture—ensuring passion and purpose drove performance. The Power of the Right Culture Whether it was Alkermes or Cerevel, Sokhom emphasized that team culture trumps individual genius . “It doesn’t matter how brilliant someone is—if they’re toxic, I don’t want them on the team.” He built what others called the “happiest team at Alkermes,” showing that joy and scientific rigor aren’t mutually exclusive. Network or Miss Out One powerful shift came when Sokhom leaned into networking—despite being an introvert. “I changed from being an extreme introvert to someone who thrives on connection.” His story underscores how something as simple as forwarding a resume or reaching out for coffee can change careers. The Lifecycle of GPCR Popularity Sokhom has witnessed the waves of scientific fashion: “There was a time GPCRs were hot, then ignored. Now they’re back.” His unwavering dedication through these cycles became an asset—many others shifted focus, leaving a smaller, highly skilled group of GPCR specialists. Lessons from Molecules and Mentors He draws inspiration from scientific complexity and colleagues like Arthur Christopoulos and Terry Kenakin. “What fascinates me is how the same molecule behaves differently depending on one amino acid.” He blends classical receptor pharmacology with biosensor technology, always adapting to new tools and insights. Don’t Let Weakness Define You The episode ends with a deeply human reflection: “Don’t let your weakness define your life. Overcome it. I used to sweat thinking about presentations. Now I love them.” Whether it’s networking, leadership, or technical mastery, Sokhom’s message is clear: keep evolving, and don’t settle. Key Takeaway Sokhom Pin's journey is a masterclass in scientific persistence , non-traditional success , and values-driven leadership . For any scientist navigating career uncertainty—his story is both roadmap and inspiration. About Sokhom Pin Sokhom Pin is a receptor pharmacologist with over 20 years of drug discovery research in the pharmaceutical industry, where he works mainly on GPCRs as therapeutic targets. He is passionate about mechanistic profiling of therapeutic molecules as well as drug discovery in general. Outside of science Sokhom enjoys outdoor activities such as hiking, boating, fishing, and biking. Sokhom Pin on the web LinkedIn Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Terry Kenakin About Dr. Terry Kenakin After obtaining a BSc in chemistry at the University of Alberta Edmonton Canada, Terry received his Ph.D. in Pharmacology from the University of Alberta, Department of Chemistry, Canada. Dr. Kenakin then moved to the UK, where he did a post-doctoral fellowship in University College London with Sir James Black. His next stop took him to Burroughs-Wellcome (BW) in Research Triangle Park (RTP) in North Carolina USA. After 7 years at BW, Dr. Kenakin joined Glaxo Inc in RTP where he remained for 25 years through iterations of Glaxo Inc, GlaxoWellcome , and finally GlaxoSmithKline . Since 2011, Terry works at the Department of Pharmacology at the University of North Carolina School of Medicine Chapel Hill NC. His interests are in receptor pharmacology, allosteric protein function, and drug discovery. Dr. Terry Kenakin on the web LinkedIn UNC Department of Pharmacology Amazon ResearchGate Pubmed . Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Brian Shoichet About Dr. Brian Shoichet BSc in Chemistry from MIT, Ph.D. with Tack Kuntz at UCSF; Postdoc with Brian Matthews in protein stability-activity tradeoffs, crystallography; started my independent lab at Northwestern University Medical School (1996) was recruited back to UCSF in 2003. Dr. Brian Shoichet on the web Google Scholar Shoichet Lab Twitter Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

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<< Back to podcast list Strategic Partner(s) You never know where your GPCR takes you with Dr. Brian Hudson About Brian Hudson Brian is a lecturer in the School of Molecular Biosciences at the University of Glasgow. He has more than 20 years of experience in GPCR, primarily focused on drug discovery and developing new tools to study this receptor family. He leads a research group that is focused on understanding the pharmacology and function of a group a GPCRs that are activated by metabolic intermediates. Brian Hudson on the web University of Glasgow Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Alessandro Nicoli shares how he models olfactory GPCRs with AlphaFold, mentors students, and builds science from scratch in a new lab. A fresh look at computational GPCR research. << Back to podcast list Strategic Partner(s) Smells Like GPCR Spirit: Cracking Olfactory Codes with Alessandro Nicoli The Accidental Path to Science Alessandro Nicoli didn’t grow up knowing he’d be a scientist. Like many, his path to GPCR research wasn’t linear—it evolved through academic exploration and mentorship. “I think I don’t have a linear trajectory… the beauty of seeing molecule design and reactions—thinking you can create molecules—was really exciting.” – Alessandro Nicoli He studied pharmaceutical chemistry in Padua, where his fascination with molecular design first took shape. But it wasn’t until meeting an inspiring professor, Prof. Moro, that he truly saw how molecules could go beyond the bench and interact with biology in powerful ways. The Moment Chemistry Met Biology Nicoli’s turning point came when he realized that molecules weren’t static—they could act , bind , and modulate biological targets. “It was not just a molecule—it was a partner that goes to interact with something else… a protein, DNA, RNA. That opened up a new world.” – Alessandro Nicoli That early spark led him to discover the role of medicinal chemistry and, eventually, molecular modeling. For Nicoli, chemistry became more than reactions—it became a bridge to biological insight. Falling for Computational Chemistry The "second academic love" arrived during his master’s thesis, where Nicoli dove into computational chemistry. “I got to know computational chemistry through a project on BCL2 proteins and drug discovery… I was in love with the topic.” – Alessandro Nicoli Working on docking and NMR studies for cancer-related proteins, he discovered the power of simulation in revealing molecular interactions. That experience convinced him to pursue a PhD and deepen his computational skills—eventually leading him to GPCRs. Finding the Right Mentor and Lab A birthday email changed everything. Professor Moro forwarded a PhD opening from Prof. Antonella Di Pizio’s lab in Munich. It felt serendipitous—and it was. “We had a super match… and after a month, I was already in Germany. I was her first PhD student.” – Alessandro Nicoli Starting from scratch in a young lab wasn’t easy, but it created a unique bond between PI and student. Nicoli thrived in this setting—helping shape the lab and its direction, particularly in computational studies of olfactory GPCRs . GPCRs, Receptors of Infinite Variety When asked about his favorite GPCR, Nicoli refused to pick. “Let’s embrace the challenge to study all of them… they’re unique in how they bind ligands, how selective they are.” – Alessandro Nicoli He emphasized that olfactory receptors , while underexplored, present an incredible challenge. With hundreds of subtypes and very few known ligands, the structure–function relationships remain largely mysterious—and incredibly exciting for a computational chemist. AlphaFold: A Turning Point in GPCR Research When Nicoli began his PhD, AlphaFold hadn’t yet revolutionized the field. But once released, it changed everything. “AlphaFold gave us a face to those proteins… now we have 400 models to start with.” – Alessandro Nicoli He explained how AlphaFold’s predictions, surprisingly close to experimental structures, provided a powerful starting point for docking, dynamics, and ligand design—especially for receptors previously “invisible” to structural biology. Modeling the Invisible: Olfactory Receptors Nicoli’s work centers on predicting ligand binding and receptor behavior for olfactory GPCRs. “The main challenge was: how do we get a face for these proteins when we don’t have ligands?” – Alessandro Nicoli He shared a detailed case study of working on a specific odorant receptor (R5VK1), where they leveraged known active/inactive ligands to validate models through iterative refinement , molecular docking , and mutagenesis-guided optimization . The goal? Build predictive models to discover new ligands . Why Molecular Dynamics Matters For Nicoli, molecular dynamics is more than simulation—it’s how we watch biology move . “You simulate over time… see how receptors move in physiological conditions, with water, membranes, ligands.” – Alessandro Nicoli He emphasized that MD allows researchers to observe allosteric changes , mutation effects , and even ligand entry/exit paths , offering dynamic insights that static structures cannot. It’s a critical complement to experimental work. From Researcher to Mentor: Growing Together Outside his research, Nicoli mentors students, manages interns, and even lectures. Balancing this with a PhD isn't easy, but it’s deeply rewarding. “You have people that rely on you… but you grow together, and that’s the most powerful thing.” – Alessandro Nicoli He reflected on learning to delegate—how hard it was initially to hand over tasks—but how vital it is for team science. He now sees mentoring as a way to shape the next generation while evolving himself as a scientist. Advice, Tools, and the Future of GPCR Research Nicoli offered advice to wet-lab scientists curious about computational work: Start with passion. Learn Python. Explore online resources like “Talktorials.” “We’re living in a golden era for computational chemistry… the tools are out there. You just need the motivation to explore.” – Alessandro Nicoli As for what’s next? More structures, better tools, and deeper insights into the elegant, complex world of GPCRs. He sees a future where wet and dry labs converge , and where computational methods are fully integrated into GPCR drug discovery pipelines. Key Takeaway Alessandro Nicoli’s journey is a compelling example of how computational chemistry can unlock new frontiers in GPCR research , especially in complex areas like olfactory receptors. By bridging structural prediction, molecular dynamics, and ligand discovery, his work not only deciphers biological mysteries but also inspires a new generation of scientists to think computationally. About Alessandro Nicoli Alessandro Nicoli is currently a PhD student in the Molecular Modeling group led by Prof. Dr. Antonella Di Pizio at the Leibniz Institute for Food Systems Biology at the Technical University of Munich (Germany). He obtained an MSc degree in Chemistry and Pharmaceutical Technology from the University of Padua (Italy). His training and passion for computational chemistry started in 2019 during his time at the Molecular Modeling Section (MMS) under the supervision of Prof. Stefano Moro, where he worked on integrated Nuclear magnetic resonance (NMR) and computational modeling strategies to target the antiapoptotic BCL-2 protein family, key regulators of cell survival, using small molecules. He then moved to Germany in 2019 to pursue his PhD. His research focuses on a group of 400 transmembrane proteins known as olfactory receptors, which mediate the sense of smell. Beyond the olfactory epithelium, these receptors are expressed in various tissues, where they play important but not yet fully understood roles in various physiological and pathological processes. Despite their relevance, they remain understudied due to the limited knowledge of their ligands and the lack of experimental structures. Alessandro PhD work aims to fill these gaps by leveraging computational structure-based tools and develop specific protocols to accelerate OR ligand discovery and improve our understanding of olfactory function at the molecular level. Alessandro Nicoli on the web Leibniz Institute for Food Systems Biology at the Technical University of Munich Technical University of Munich Google Scholar Pubmed ORCID ResearchGate X Bluesky Github Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Ilana Kotliar About Dr. Ilana Kotliar "Ilana Kotliar is a postdoctoral associate in the lab of Tom Sakmar at The Rockefeller University, where she just recently defended her PhD thesis. Ilana uses chemical biology-based methods to study the regulation and protein-protein interactions of GPCRs and a small family of accessory proteins called RAMPs. Ilana’s research is multi-disciplinary and involves a close collaboration with proteomics experts at The Science for Life Laboratory in Sweden. She is a recipient of the prestigious Women in Entrepreneurship Award, an NIH T32 Training Grant, and two Nicholson Fellowships. Outside of the lab, Ilana is a leader within her community, spearheading several outreach initiatives including a global mentoring initiative that matches graduate student mentors to PhD applicants. Ilana graduated Summa cum laude from Cornell University, where she studied Chemistry and Chemical Biology and was recognized as a Merrill Presidential Scholar." Dr. Ilana Kotliar on the web Google Scholar LinkedIn Twitter Dr. GPCR Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Josh Pottel About Dr. Josh Pottel "I lead Molecular Forecaster Inc. (MFI): a reliable, self-sustaining computational chemistry service provider, developing its own software for application in various drug discovery campaigns. I have extensive training in computer-aided drug design. I completed my PhD at McGill University in the lab of Prof. Nicolas Moitessier, and went on to a postdoc with Prof. Brian Shoichet at UCSF. While in San Francisco, I completed Startup101 - a course a offered by the entrepreneurship center. I am now combining my training as a chemist and as an entrepreneur to grow a sustainable service and software provider in drug discovery. More broadly, I hope to be a critical contributor to a growing Canadian biotech sector in both scientific research and fostering entrepreneurship." Dr. Josh Pottel on the web Molecular Forecaster LinkedIn BlueSky Google Scholar Twitter Dr. GPCR Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

When his lab closed in 2020, Dr. Paul Insel turned dry-lab science into a reframing of COVID-19 pathobiology as a GPCR signaling imbalance — and a figure in The Economist. << Back to podcast list Strategic Partner(s) Paul Insel: Rethinking COVID-19 Pathobiology Through GPCR Signaling In the spring and summer of 2020, pharmacologist Dr. Paul Insel did something unusual for a working lab scientist: he stopped pipetting, and started writing. With his UC San Diego postdoc Krishna Sriram, he reread the literature on ACE inhibitors and angiotensin receptor blockers in the context of severe acute respiratory illness and concluded — against a swell of clinical panic — that the case for their danger in COVID-19 didn't hold up. What came next was a series of papers reframing severe COVID-19 as a disease of signaling imbalance: an overdrive of AT1R activation by angiotensin II, paired with a loss of ACE2-generated angiotensin 1-7. The therapeutic logic that follows is less about attacking the virus and more about rebalancing a GPCR-driven system that the infection has thrown off-axis. A figure from that British Journal of Pharmacology paper was later redrawn by The Economist for a general-audience article on COVID pathobiology — an unexpected crossover for work that began as armchair science during a lockdown walk. This conversation matters to Dr. Insel personally because he is, in his own words, a vulnerable patient — immunosuppressed, older, asthmatic — and what he's describing is not abstract. It's what he would want a physician to understand if he were the one in the hospital bed. About the Guest Dr. Paul Insel is Distinguished Professor of Pharmacology and Medicine at UC San Diego, where he also co-directs the MD-PhD program. His research career has centered on GPCR signaling — with particularly deep work on beta-adrenergic receptors, cyclic AMP regulation, and receptor biology across tissue systems. Beyond the lab, he has been a long-standing contributor to the Goodman & Gilman textbook of pharmacology and is writing its next chapter on angiotensin signaling and angiotensin drugs. He is also involved nationally in MD-PhD program leadership. Scientific Themes of the Conversation The angiotensin imbalance hypothesis of COVID-19 pathobiology — AT1R overdrive versus ACE2/Ang 1-7 insufficiency Drug repurposing as a pandemic strategy — from ACE inhibitors and ARBs to PAR1 and PAR4 antagonists The "gas pedals and brakes" philosophy of cell signaling and pharmacology Dry-lab pharmacology and what becomes possible when wet-lab work stops GPCR density and tissue-specific therapeutic opportunity — type II pneumocytes, beta-2 receptors, and the asthma parallel The ethics of acting on conviction — off-label drug use during a pandemic Key Insights from the Conversation The ACE inhibitor scare was built on a bogus reading of the literature. Early in the pandemic, senior clinicians were stopping their own ACE inhibitors and ARBs based on hypothesis-driven fears of worse outcomes. Dr. Insel and Krishna Sriram went to the primary data and concluded the claim was not supported. The review was accepted at Clinical Pharmacology and Therapeutics within weeks. Severe COVID-19 may be a story of signaling imbalance, not just viral damage. The British Journal of Pharmacology paper reframes pathobiology as an imbalance between AT1R activation and ACE2-generated angiotensin 1-7. If the virus disrupts one arm of this receptor-peptide system, the therapeutic question stops being "what do we add?" and becomes "what do we rebalance?" Biology runs on opposing forces, and good pharmacology learns to see them. Kinases and phosphatases. Cyclases and phosphodiesterases. ACE1 and ACE2. Dr. Insel returns repeatedly to his "gas pedals and brakes" frame — a lens that has quietly shaped how he reads both disease mechanism and drug targets across a long career. The lung's beta-2 story has been sitting in plain sight for fifty years. Type II pneumocytes carry the highest beta-2 receptor density in the body. Long-acting beta-agonists paired with glucocorticoids have been the mainstay of asthma treatment for decades. The connection to acute respiratory distress syndrome — and to the mechanism through which dexamethasone actually works — is, in his reading, underdiscussed rather than speculative. "Don't just do something. Stand there." A clinical mentor's line that became the frame for the lockdown months. Four papers in roughly two months — what Dr. Insel calls armchair science. Not casual, not opinion-writing; dry-lab pharmacology done with the same seriousness as bench work, just with different tools. A figure can travel further than the paper it came from. The schematic from the BJP paper was redrawn by The Economist, with attribution, for a general-audience article on COVID pathobiology. Dr. Insel notes wryly that it's the only paper his family has ever really responded to. The ethics of acting on conviction is its own paper. Midway through writing the angiotensin work, Dr. Insel realized no one had written criteria for how to decide about off-label use of a drug during a pandemic — when mechanism is compelling, safety is reasonable, and trial evidence isn't there yet. He is writing that paper with an ethicist and a law-school colleague. It is exactly the kind of work a pharmacologist does when the lab is closed. Episode Timeline Timestamps were generated using AI for readability. 00:00 Opening and 2020 Summit context 01:45 Dry-lab science — how the work shifted when the wet lab closed 02:37 Rereading the ACE inhibitor scare — and the BJP paper that followed 07:40 Expanding the hypothesis — PAR1, PAR4, and upstream pathobiology 11:00 Gas pedals and brakes — biology's architecture of opposing forces 14:00 Type II pneumocytes, beta-2 density, and the asthma parallel 22:40 The ethics of off-label drug use during a pandemic 25:00 Genetic determinants of severity — ACE1 isoforms and population data 28:40 Vaccine development speed and public trust 33:40 Staying sane — pickleball, walking, and community Selected Quotes "Don't just do something. Stand there. That's sort of what we've been doing. And I think we've made some contributions that are pretty interesting. I really want to do something to help people. That's what this is all about, really." — Dr. Paul Insel "Almost most biological systems are all about gas pedals and brakes. We have kinases and phosphatases. We have cyclases that make cyclic AMP and phosphodiesterases that degrade it. Nature has built in these systems consistently." — Dr. Paul Insel "If you would have told me three months ago that I was going to end up having a figure in The Economist — forget about one of the science journals — in The Economist…" — Dr. Paul Insel "It's still about GPCRs." — Dr. Paul Insel About this episode Dr. Paul Insel is currently a Distinguished Professor of Pharmacology and the University of California San Diego. Paul thinks broadly about science and has been actively publishing papers about his ideas on how COVID symptoms could be treated while we wait for a vaccine, particularly about ACE2 and angiotensin. For the past 30 years, he has been the Director of MD/Ph.D. training program at UCSD and has served as Editor or Senior Editor of numerous scientific journals, including but not limited to the Journal of Clinical Investigation, Molecular Pharmacology, British Journal of Pharmacology, and American Journal of Physiology-Cell Physiology. Dr. Paul Insel on the web Insel Laboratory Institute of Engineering in Medicine UC San Diego UCSD Profiles Google PubMed Dr. GPCR Ecosystem Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. 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