Antony Boucard - the scientist who discovered that a cell adhesion molecule and a GPCR share a black widow spider toxin binding site — on adhesion GPCRs, synapse formation, and building a research program where none existed before. << Back to podcast list Strategic Partner(s) Antony Boucard: Adhesion GPCRs and the Molecular Code of Synapse Formation Adhesion GPCRs represent one of the most architecturally complex and least understood branches of the GPCR superfamily. Characterized by extracellular domains exceeding 1,000 amino acids, autoproteolytic cleavage at the membrane, and a near-total absence of characterized ligands, these receptors long resisted the molecular tools that made classical family A GPCRs tractable. Only recently has the field established, with confidence, that adhesion GPCRs couple to G proteins at all. Boucard's laboratory at UNAM in Mexico City sits at this frontier. His research centers on the molecular code governing synapse formation — how adhesion GPCRs, working alongside classical cell adhesion molecules, determine which neuronal partners recognize each other and which synaptic contacts stabilize. The work connects receptor biology to neuropsychiatric disease: addiction, autism spectrum disorder, schizophrenia, bipolar disorder, and cancer. The foundation of this program rests on a serendipitous discovery Boucard made in Thomas Südhof's lab — that a cell adhesion molecule and a GPCR, studied separately for over a decade, both bind alpha-latrotoxin from black widow spider venom, and that together they form an intercellular complex no one had previously described. For Boucard, adhesion GPCRs are not simply a research subject. They are the place where everything he has cared about — biochemistry, cell communication, disease, and the students other institutions overlooked — finally came together. About the Guest Antony Boucard is a biochemist and cell biologist who leads the Boucard Laboratory at the National Autonomous University of Mexico (UNAM) in Mexico City, where he has built one of the only research programs in Latin America focused on adhesion GPCRs. He completed graduate training in biochemistry at the Université de Sherbrooke and his postdoctoral fellowship in the laboratory of Thomas Südhof at UT Southwestern and Stanford University, where he made the initial observation linking cell adhesion molecules and GPCRs through their shared binding to alpha-latrotoxin. His current research programs span synapse formation, addiction, autism, schizophrenia, bipolar disorder, and tumorigenesis, applying cell biology, BRET and FRET assays, microscopy, flow cytometry, and custom protein engineering approaches to probe adhesion GPCR function across physiological and pathological contexts. Scientific Themes of the Conversation Adhesion GPCRs as a distinct receptor class — autoproteolytic architecture, orphan status, and the long-delayed confirmation of G protein coupling The molecular logic of synapse formation and how adhesion molecules encode synaptic specificity in the brain Alpha-latrotoxin from black widow spider venom as an experimental bridge connecting cell adhesion molecules and GPCRs Neuropsychiatric disease through the lens of adhesion GPCR biology — addiction, autism spectrum disorder, schizophrenia, and cancer The structural bottleneck: what cryo-EM cannot yet capture about receptor dynamics at the cell surface Pioneering a research field in an underrepresented scientific ecosystem, and recruiting from communities elite institutions have historically overlooked Key Insights from the Conversation 1. Adhesion GPCRs Were Not Considered Real GPCRs For decades, adhesion GPCRs were assigned to the GPCR superfamily on the basis of their seven-transmembrane topology alone — not because G protein coupling had been demonstrated. Whether they functionally coupled to G proteins remained genuinely open, and for much of the field's history, skepticism was reasonable. Boucard's work on their signaling capacity in the context of synaptic biology sits at this still-resolving frontier, where the biology is catching up to the structural classification. 2. A Forgotten Sample, a First Paper During his graduate studies, Boucard left an enzymatic reaction on his bench over a weekend — called away for army training — and returned to find results that had eluded the lab for months. He nearly discarded the sample. Running it on instinct, he obtained reproducible data that became his first publication. The pattern established there — outcomes shaped as much by openness as by design — has followed him through every phase of his career since. 3. The Black Widow Toxin Nobody Put Together Working in Südhof's lab on cell adhesion molecules, Boucard made a lateral decision: to test whether one of the proteins he was studying might bind to a GPCR he had no reason to investigate. The interaction was real. On a colleague's suggestion, he recognized that both proteins had independently been shown to bind alpha-latrotoxin from black widow spider venom — but no one had ever asked whether they interacted with each other. They formed an intercellular adhesion complex. Südhof himself was skeptical; the field had studied both proteins for over a decade without making the connection. That discovery became the foundation of Boucard's independent research program. 4. Adhesion GPCRs Open a Pandora's Box Adhesion GPCRs appear across nearly every biological process — from embryonic development to synaptic maturation, from immune cell trafficking to tumorigenesis. Boucard describes this breadth not as an opportunity but as a constraint: the challenge for his lab has been choosing which processes to study rigorously rather than chasing the full landscape. Anchoring the work in synapse formation provides a tractable and biologically meaningful lens, while the transversal logic — that what is learned about adhesion in one context often illuminates another — keeps the research portfolio coherent. 5. The Structural Bottleneck Cryo-EM has transformed understanding of classical GPCR structure, but adhesion GPCRs remain dramatically underrepresented in the structural database. The deeper issue, Boucard argues, is not just the quantity of structures but their nature: every cryo-EM image is a frozen moment, capturing a receptor in one state, in one membrane environment, at one point in time. What the field still cannot do is observe the dynamics of receptor assembly, complex formation, and signaling in real time at the cell surface. That gap is where the most important biology is happening. 6. Choosing Mexico City as a Scientific Bet After postdoctoral and faculty positions at Stanford and UT Southwestern, Boucard surveyed the conventional research markets — North America, Western Europe — and concluded that his skills were not especially scarce there. Mexico City offered something different: a research territory in adhesion GPCR biology that was entirely unoccupied, a massive university drawing students from across Latin America and indigenous communities within Mexico, and a scientific culture where his particular combination of biochemistry, cell biology, and translational thinking could do something that wasn't already being done. Eight years in, he has not reconsidered the decision. Episode Timeline Timestamps were generated with AI assistance from the episode transcript and may not reflect exact segment boundaries. Use them as navigational guides. 00:00 Sponsor intro — GeneTex & Eurofins DiscoverX 00:43 Introducing Boucard: a scientific path that was never planned 01:40 From biochemistry by accident: Sherbrooke, Dallas, Stanford, Mexico City 03:43 The summer lab that changed everything — and why he turned down medical school 10:23 Army service, social work in Nicaragua, and the civil war that reframed resources and risk 16:18 Turning down the medical school acceptance — 25 years of no regrets 22:10 Université de Sherbrooke's industry-integrated curriculum and what it modeled about flexibility 26:06 Surviving crisis in Haiti and what scarcity teaches about choice 31:33 The underground restaurant in San Francisco, born out of an immigration emergency — and Chef's Table Season 2 43:45 Time, focus, and the discipline of 15 minutes a day 52:38 Why Mexico City: building a lab for students no one else was recruiting 01:00:00 Adhesion GPCRs — the receptor family that kept calling him back 01:04:58 The black widow toxin discovery — two proteins, 15 years of prior research, one untested pair 01:06:18 Why adhesion GPCRs are among the hardest receptors to work with, and why structures are finally coming 01:09:10 Synapse formation, addiction, autism, schizophrenia, and cancer: the lab's research logic 01:13:45 Assays: BRET, FRET, microscopy, flow cytometry, and engineering membrane-anchored ligands into solution 01:19:29 The dream tool — a nanoscale camera navigating the cell surface in real time 01:22:24 Advice to junior scientists: don't be afraid to be afraid 01:26:00 Three aha moments: socks, a forgotten sample, and one cold email to a Nobel laureate 01:35:33 Lab openings and where to find the Boucard Lab Selected Quotes "Every single one of my days right now has been just to reconstruct what I learned the day before. That's something that I really love — you kind of put yourself in the mindset of the kid once again." "A lot of people say there's a lot of reasons not to do an experiment. There's a ton. But sometimes you can just do one. And you never know." "I can't believe you won the Nobel Prize. Because at home, he can't even pick up his own socks." — Said to Boucard by a fellow Nobel laureate's wife, at a ceremony at Stanford, following the 2013 prize announcement "If you willingly put yourself in a situation where you're willing to take risks, things will fall into place. But if you never try, you might not know. And whether you're there for a short time or for the rest of your life, you'll have the best time of your life during the time you're doing it." About Dr. Antony A. Boucard Jr. Dr. Antony Boucard joined the Université de Sherbrooke (Québec, Canada) as a B.S. student of the Biochemistry program in 1994 from which he graduated in 1997. It is then that his interest bloomed for the study of GPCRs while joining the group of Dr. Richard Leduc and Dr. Gaetan Guillemette in the Pharmacology department at the Université de Sherbrooke. He completed a master’s degree in 2000 and a Ph.D. degree in 2003 with a particular interest in the cardiovascular system by investigating the structure of the Angiotensin and Urotensin receptors through various biochemical approaches centered in the elucidation of ligand binding pocket determinants. Motivated by a new ambition to study the nervous system, Dr. Boucard pursued postdoctoral training at the University of Texas Southwestern Medical Center in Dallas where he joined the group of Dr. Thomas Südhof . In this institution dear to the heart of GPCR enthusiasts given that its faculty personnel included Dr. Alfred Gilman , Nobel Laureate for his discovery of G proteins, Dr. Boucard ventured into the field of synaptic adhesion molecules which would eventually prompt him to investigate the role of a peculiar family of GPCRs belonging to the Adhesion subgroup. After a relocation to Stanford University where he pioneered work on ligand discovery for then orphan adhesion GPCRs, Dr. Boucard moved to Mexico City to establish himself as an independent investigator integrating the department of Cell Biology at the Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (Cinvestav-IPN). Dr. Boucard´s lab focuses on molecular and cellular mechanisms underlying the function of adhesion GPCRs in the formation of synapses. Having a particular interest for a three-member family named latrophilins, his lab seeks to decipher the molecular code instructing adhesion events mediated by these GPCRs. The pharmacology of latrophilins brings about a great deal of challenges given that they are highly polymorphic proteins expressed as various alternatively spliced isoforms thus potentially resulting in differential modulation of cell signaling pathways. His lab highlighted the importance of splicing events in biasing latrophilins’ regulation of cyclic AMP pathways and for determining the magnitude of ligand selectivity. Additionally, his team is also interested in understanding the pathophysiological relevance of latrophilins’ function in neuropsychiatric disorders given their association with genetic susceptibility to the neurodevelopmental disorder known as attention deficit hyperactivity disorder (ADHD) but also to a comorbid clinical manifestation linked to addiction. He also actively volunteers as an Associate Professor of the non-governmental organization Institut des Sciences, des Technologies et des Etudes Avancées d’Haïti (ISTEAH) to help consolidate higher education in Haiti. Dr. Antony A. Boucard Jr. on the web Website LinkedIn Researchgate Loop Academia Pubmed Adhesion GPCR Consortium University of Haiti Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. 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Structural biologist Qing Fan describes a decade of GABA-B receptor research at Columbia - from obligate heterodimerization and the inter-subunit latch to an unexpected discovery of phospholipids inside the transmembrane bundle, and what class C GPCR architecture means for neurological disease and drug design. << Back to podcast list Strategic Partner(s) Qing Fan: Inside the Architecture of Class C GPCRs Class C GPCRs are structural and mechanistic outliers within the GPCR superfamily. Unlike class A receptors, which bind orthosteric ligands within their transmembrane domain and can function as monomers, class C receptors carry an additional extracellular domain of 500 to 600 amino acids that houses the agonist binding site - and they require dimerization as a prerequisite for function. Despite the clinical significance of their members, particularly the GABA-B receptor, the metabotropic glutamate receptors, and the calcium-sensing receptor, the molecular mechanisms governing their activation and regulation remain incompletely understood. Fan's laboratory at Columbia University has spent more than a decade investigating the three-dimensional architecture of the GABA-B receptor - the first known obligatory GPCR heterodimer - across multiple functional states. Her work has produced structural data at the extracellular domain level and, more recently, full-length cryo-EM structures in inactive conformation, leading to an unexpected discovery: phospholipids embedded inside each transmembrane bundle that appear to function as both structural anchors and negative allosteric modulators. This conversation covers the current structural landscape of class C GPCRs, how genetic disease mutations in the transmembrane domain connect to Rett syndrome and epileptic encephalopathy, and what allosteric and biased signaling strategies could offer that baclofen - the only FDA-approved GABA-B drug - cannot. Fan's commitment to this receptor began with a single structural observation during her postdoc: dimers forming in an FSH receptor crystal that she could not set aside. ABOUT THE GUEST Qing Fan is an associate professor of pharmacology and pathology and cell biology at Columbia University. A structural biologist by training, her research focuses on the three-dimensional architecture of class C GPCRs - with particular emphasis on the GABA-B receptor, which she has studied as her primary independent research question for over a decade. Her work employs X-ray crystallography, single-particle cryo-EM, mutagenesis, and mass spectrometry, often through cross-disciplinary collaboration, to connect structural findings to receptor function and disease-relevant biology. Fan's structural studies of the full-length GABA-B receptor contributed to a wave of publications that, in the same year, established inactive, active, and intermediate conformational states of this receptor using cryo-EM. SCIENTIFIC THEMES OF THE CONVERSATION The structural architecture that sets class C GPCRs apart from class A - and why that architecture makes activation harder to study Obligate heterodimerization as a functional requirement, not a regulatory option The unexpected discovery of embedded phospholipids inside the GABA-B transmembrane bundle and their role as structural and allosteric components Disease-associated mutations in the GABA-B transmembrane domain and what they suggest about precision pharmacology The therapeutic landscape of GABA-B: baclofen's limitations and the case for allosteric and biased approaches Cryo-EM as a catalyst for structural pharmacology - what it enabled and what it still cannot resolve KEY INSIGHTS FROM THE CONVERSATION Class C GPCRs carry a fundamentally different activation logic In class A receptors, the orthosteric ligand binds inside the transmembrane bundle and directly induces conformational changes that activate the receptor. In class C receptors, the orthosteric site sits inside a large extracellular domain that is physically remote from the transmembrane core. How the agonist binding event at the extracellular level is communicated downward to activate the transmembrane domain remains an open mechanistic question - and it is the central problem Fan's laboratory is trying to answer. Dimerization is not optional - it is the mechanism GABA-B is an obligate heterodimer: the GABA-B1 subunit carries the agonist binding site; the GABA-B2 subunit is required for trafficking to the cell surface and for G protein coupling. Neither subunit functions without the other. Fan's structural work identified a quartet of charged residues - salt bridges between TM3 and TM5 helices of both subunits - that she terms the inter-subunit latch. Disrupting this latch through mutagenesis produces constitutive receptor activity, suggesting it is a critical component of the receptor's inactive state. Phospholipids inside the transmembrane bundle: a discovery nobody expected When Fan's team solved the full-length cryo-EM structure of inactive GABA-B, they found a bulky phospholipid occupying the internal cavity of each TM bundle. Using mass spectrometry in collaboration with colleagues at UC Davis, they identified the exact molecular identity of both lipids and assigned one to each subunit based on head group size differences. Both lipids form extensive contacts with their respective subunits, leading Fan to propose they are necessary structural components - not incidental contaminants. Mutational analysis of the GABA-B2-bound lipid site further suggested that lipid acts as a negative allosteric modulator, though Fan is careful to note that more thorough characterization is needed before conclusions can be drawn about each lipid's specific functional role. Rett syndrome and epilepsy mutations point directly to the transmembrane domain Single amino acid mutations in GABA-B2 have been linked to Rett syndrome and epileptic encephalopathy. These mutations map to the transmembrane domain - the same region where Fan's team identified the embedded lipid binding site. The proximity raises the question of whether some disease mutations exert their effects by disrupting lipid-receptor interactions. Fan describes the resolve-the-disease-isoform-structure approach as underutilized: most structural work focuses on wild-type receptors, while patients with genetic disease are born with receptors that may behave very differently - and that may respond differently to existing drugs. Baclofen works. But its therapeutic window is narrow. Baclofen, a selective GABA-B agonist, is the only FDA-approved drug targeting this receptor. It is used to treat muscle spasticity in multiple sclerosis and spinal cord injury, but it carries significant side effects - including drowsiness and weakness - that limit its clinical utility. Fan describes the allosteric sites within the transmembrane domain as a more targeted alternative: they offer receptor modulation without directly competing with the endogenous agonist at the orthosteric site, and they map onto the same transmembrane region where disease-relevant mutations cluster. The biased agonism framework still offers real specificity - if applied carefully Fan points to the 2016 work on the mu opioid receptor by Kobilka, Gnäder, Roth, and Shokat as an illustration of what pathway-selective drug design can achieve: a compound that confers analgesia through G protein signaling while avoiding the respiratory depression associated with beta-arrestin pathway activation. She acknowledges the field's more recent reassessment of how clean that selectivity actually is in vivo - but holds that the underlying principle of fine-tuning rather than binary pathway switching remains a viable and underexplored pharmacological strategy for GPCR-targeted drug design. A decade on one receptor: the cost and the clarity it produces Fan has worked on the GABA-B receptor since it became her first independent project. Over more than ten years, the questions have deepened rather than resolved: the lipid finding opened new lines of inquiry; the disease mutation connections raised new structural puzzles; the cryo-EM structures raised as many mechanistic questions as they answered. Her description of this trajectory is not frustration - it is the argument for sustained focus. The field has moved from not knowing the subunit composition of GABA-B to holding cryo-EM structures in inactive, active, and intermediate states. That arc is the product of a community of researchers willing to stay with one system long enough to see it clearly. EPISODE TIMELINE Timestamps are AI-generated approximations based on transcript markers and may not reflect exact positions in the final edited video. 00:00 - Opening announcements 01:26 - Fan's background as a structural biologist and path to class C GPCRs 04:39 - Why class C GPCRs remain the less-explored side of the GPCR superfamily 05:11 - The architecture of GABA-B: extracellular domains, obligate heterodimerization, and field milestones since the 1970s 11:02 - The unexpected cryo-EM finding: phospholipids embedded inside each transmembrane bundle 12:55 - What the lipids actually do - structural components, allosteric modulation, and open questions 14:57 - Disease territory: epilepsy, spasticity, pain, addiction, and the limitations of baclofen 16:17 - The case for resolving disease isoform structures as a path toward precision medicine 19:03 - GPCRs as drug targets: allosteric sites, biased signaling, and what the mu opioid receptor example demonstrated 23:37 - What full-length structures in multiple states still need to deliver for drug design 25:01 - Advice for early-career scientists: the role of passion in sustained scientific work 26:15 - Three "aha" moments that shaped a career - from MHC antigen presentation to the cryo-EM revolution 29:55 - Increasing diversity in science through mentorship, structured Q&A, and institutional commitment SELECTED QUOTES "My favorite is still the GABA-B receptor since it was my first independent project and my lab has been working on it for more than a decade now." "One of our surprising findings is the discovery of a bulky phospholipid that occupied the internal cavity of each TM bundle." "Ligands that display biased signaling property may serve as highly specific drug candidates. And this feature opens more room for selecting a specific effect without also interfering with other cell processes." "I would advise young scientists to follow their interests and to work on projects that they're passionate about and not simply projects that may attract more funding. Their passion will keep them going even when they encounter difficulties." About this episode Dr. Fan is currently an associate professor of Pharmacology and Pathology and Cell Biology at Columbia University in NYC. Qing is a structural biologist interested in the molecular mechanisms controlling how class C GPCRs transmit signals. She obtained her bachelor's, master and doctoral degrees at Harvard University and completed her postdoctoral training with Dr. Hendrickson at Columbia University. Join us and learn more about Qing's work and how we powered through a technical issue during the interview. Dr. Qing Fan on the web Fan Lab Dr. Fan at Columbia University Research Gate LinkedIn Pubmed Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. 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<< Back to podcast list Strategic Partner(s) Dr. Patrick Sexton About Dr. Patrick Sexton Patrick Sexton is a Professor of Pharmacology, National Health and Medical Research Council of Australia Senior Principal Research Fellow, and Director of the Australian Research Council Centre for Cryo-electron Microscopy of Membrane Proteins ( www.ccemmp.org ). He is a leader in the study of GPCRs, biased agonism, and also on allosteric interactions between GPCRs and other proteins and small molecule ligands. More recently, his team has been at the forefront of the application of cryo-EM to elucidate of the structure and dynamics of GPCRs. Prof. Sexton has published over 320 peer-reviewed journal articles and has been cited >26,000 times (Google Scholar). He is a 2021 Clarivate Analytics Highly Cited Researcher in two disciplines: Pharmacology & Toxicology and Biology & Biochemistry, a corresponding member of the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification, and a member of the Faculty of 1000 (Molecular Pharmacology division) and an elected Fellow of the British Pharmacological Society (BPS). Prof. Sexton’s awards include the Australasian Society for Clinical and Experimental Pharmacologists and Toxicologists (ASCEPT) Lecturer award, Endocrine Society of Australia Senior Plenary award, Rand Medal (ASCEPT), Paxinos-Watson Award (Australian Neuroscience Society), Vane Medal (BPS), Gordon Hammes Lectureship Award (American Chemical Society) and the GSK Research Excellence award. Prof. Sexton is also a co-founder of the San Francisco-based biotechnology company Septerna Inc . Dr. Patrick Sexton on the web CCeMMP Monash University Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Randy Hall on the receptor tail the field ignored, the adhesion GPCR experiment that did the opposite of what he expected, and writing Lefkowitz's memoir. << Back to podcast list Strategic Partner(s) Randy Hall: Adhesion GPCRs and the Tail Nobody Wanted SCIENTIFIC ABSTRACT Most of what the field now takes for granted about the C terminus of a GPCR was, in the mid 1990s, considered uninteresting. Randy Hall arrived in Bob Lefkowitz's lab from a background in ionotropic glutamate receptors, noticed that the beta adrenergic receptors carried short motifs resembling the ones that recruit scaffold proteins to NMDA receptors, and asked what bound there. He was told the answer was nothing. At the time, the lab chasing the first GPCR crystal structure was cutting the tail off entirely. What he found reframed how the field explains why closely related receptor subtypes produce different effects on cell physiology. This conversation follows that thread into adhesion GPCRs, a subfamily of 33 human receptors with enormous extracellular N termini that cleave themselves and then stay together. Hall describes the experiment designed to kill receptor signaling that instead amplified it, the tethered agonist model his lab proposed in 2011, and why a family once dismissed as undruggable now looks like a serious therapeutic frontier. He also explains how he came to write the memoir of his mentor, a project he pitched three times over fifteen years before the answer was yes. ABOUT RANDY Randy Hall is Professor of Pharmacology and Chemical Biology at Emory University School of Medicine, where he has run his lab since 1999. He trained with Gary Lynch at UC Irvine on ionotropic glutamate receptors, then with Thomas Soderling at the Vollum Institute on receptor trafficking and phosphorylation, before joining Bob Lefkowitz's lab at Duke to work on adrenergic receptor regulation. His lab uses proteomic and interaction screening approaches to map the proteins that bind GPCR intracellular tails, and has published on receptors from the adrenergic, purinergic, glutamatergic, GABAergic and adhesion subfamilies. Recent work centers on GPR37 and GPR37L1 and on the adhesion receptors BAI1, BAI2 and GPR56, with a particular focus on disease associated mutations that disturb receptor signaling or trafficking. He is a Fellow of the AAAS and coauthor, with Bob Lefkowitz, of the 2021 memoir A Funny Thing Happened on the Way to Stockholm. SCIENTIFIC THEMES OF THE CONVERSATION - Why the GPCR C terminus turned out to determine subtype specific function - Adhesion GPCRs: self cleaving receptors, huge N termini, and the tethered agonist model - Constitutive activity as a disease mechanism, from the alpha 1 receptor to BAI2 - Orphan receptors and where the next generation of GPCR drugs will come from - In silico screening, and what human plus machine collaboration means for drug discovery - Problem selection: how young scientists choose what to spend years on - Writing a scientific memoir, and why honesty is the load bearing part KEY INSIGHTS FROM THE CONVERSATION Changing subfields is when discovery happens Hall deliberately chose a second postdoc in a different receptor family rather than extending his graduate work. He argues that staying close to a hot topic feels safe but narrows a scientist's development, and that the moment you carry one field's questions into another is often the most productive window of a career. His own case is the evidence: NMDA receptor scaffolding logic applied to beta adrenergic receptors. The tail everyone was discarding When Hall asked what the C termini of the beta adrenergic receptors did, the lab's answer was that they could be removed with G protein coupling intact. The structural effort underway at the time simply deleted them. That consensus is precisely why he went looking, and the distinct binding partners he found for beta 1 and beta 2 offered an explanation for how two subtypes coupling to the same G protein can have opposite effects on cell physiology. Skepticism first, then a crowded field The early data drew hard questions at Gordon conferences from senior figures who were not convinced. Within a few years, dozens of labs were running similar studies across every GPCR subfamily. Hall describes the real measure of acceptance as the moment other groups start doing the experiments themselves. The experiment that did the opposite Predicting that an endogenous ligand acted on the large N terminus of GPR56, his lab truncated it, expecting a dead receptor. Signaling increased massively instead, and the same held for BAI1. That inversion became the basis for the model his lab proposed in 2011, in which removing or reconfiguring the N terminus unveils a cryptic tethered agonist, and it has since been reproduced across the family by other groups. From undruggable to promising Drug development veterans long treated large adhesive proteins as poor targets because their interaction interfaces are too big to disrupt with small molecules. Hall's counterpoint is that adhesion GPCRs are not only adhesive proteins, they are also GPCRs, with a seven transmembrane pocket. Screening work has since produced agonists and antagonists, and the first cryo EM structure of an adhesion GPCR, GPR97, showed glucocorticoid binding, raising the possibility that steroid activation of G protein pathways has been hiding in this family. When receptors are tuned and mutations detune them The BAI2 mutation Hall's lab linked to a neurodegenerative condition sits on the C terminus and makes the receptor constitutively overactive, pointing back to the protein interactions he has studied since the 1990s. He traces the concept to basic work by Susanna Cotecchia on the alpha 1 receptor in the early 1990s, research with no clinical intent that became the template for explaining a long list of human diseases. Choose important problems, not easy ones Hall's advice to junior scientists is that trivial questions are not measurably easier to solve than important ones, so the years spent are better invested in something that matters. He recommends heading for subfields in turmoil, where there is disagreement and unsolved mystery, with the single constraint that the technology to answer the question must already exist. EPISODE TIMELINE Timestamps were generated using AI for readability. - 00:00 Opening announcements - 01:34 Introducing Randy Hall - 02:02 The Feynman book, and pitching a memoir to Bob Lefkowitz three times - 06:45 Deciding which stories survive, and finding a publisher who believed in science memoirs - 17:03 Nature walks, synaptic plasticity, and falling for the first event in cell signaling - 19:39 Switching subfields, and spotting a motif nobody was looking at - 23:51 Pushback at Gordon conferences, and what acceptance actually looks like - 26:34 Moving the lab toward orphan and adhesion GPCRs - 34:00 The truncation that was supposed to kill signaling - 37:34 Pulling the pin from the grenade: the tethered agonist model - 39:38 Are adhesion GPCRs druggable, and what GPR97 changed - 46:46 In silico screening, chess, and humans working alongside machines - 52:09 Disease mutations across the adhesion family - 1:00:41 Choosing important problems over easy ones - 1:07:10 Openings in the Hall lab SELECTED QUOTES "That was how lowly regarded the C terminus was. They were just throwing it in the trash." "Go for subfields where the seas are rough and the sky is dark and there are a lot of mysteries." "If you are surprised by the result of your own experiment, then probably other scientists will also be surprised." "There is no connection between the importance of a problem and how easy it is to solve." GUEST LINKS - Hall Lab: http://www.pharm.emory.edu/hall/index.html - LinkedIn: https://www.linkedin.com/in/randy-hall-79923839 - Google Scholar: https://scholar.google.com/citations?user=tfsXwHUAAAAJ&hl=en&oi=ao - ResearchGate: https://www.researchgate.net/profile/Randy-Hall - A Funny Thing Happened on the Way to Stockholm: https://www.simonandschuster.com/books/A-Funny-Thing-Happened-on-the-Way-to-Stockholm/Robert-J-Lefkowitz/9781643136387 - Dr. GPCR Ecosystem: https://www.ecosystem.drgpcr.com/search?q=Randy+Hall Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

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

<< Back to podcast list Strategic Partner(s) Dr. Matthew Eddy About Dr. Matthew Eddy Matthew Eddy earned his BA in Chemistry from Oberlin College, where he trained with solid-state NMR expert Professor Manish Mehta . He then earned his Ph.D. in physical chemistry from the Massachusetts Institute of Technology, training under the mentorship of Prof. Robert Griffin . Following this, Dr. Eddy began learning and investigating human GPCRs while training in the laboratories of Professors Raymond Stevens and Kurt Wüthrich at The Scripps Research Institute. Dr. Matthew Eddy on the web Website Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

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

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

<< Back to podcast list Strategic Partner(s) Dr. Thomas P. Sakmar About Dr. Thomas P. Sakmar Tom Sakmar is a physician-scientist and professor at Rockefeller University in New York. While a chemistry undergraduate student at the University of Chicago, he attended a NATO Advanced Study Institute in Les Houches, France in 1979 where he was exposed for the first time to the nascent field of membrane biophysics and intercellular communication. Instructors at the course included Marc Chabre , Harden McConnell , Richard Henderson , Martin Rodbell , Jean-Pierre Changeux , and Martin Karplus . After medical school and clinical training at Massachusetts General Hospital, Tom joined the laboratory of H. Gobind Khorana at the Department of Chemistry at M.I.T. for postdoctoral training, where he learned gene synthesis, cDNA cloning, site-directed mutagenesis, and heterologous expression in mammalian cells. Khorana’s lab made early key contributions and developed strategies to express, reconstitute and assay engineered GPCRs using the visual pigment rhodopsin as a model system. Tom initially focused on structure-activity relationships underlying spectral tuning and identified a glutamic acid residue in rhodopsin that serves as the retinylidene Schiff base counterion. He also went on to discover a “counterion switch” in visual pigments and to develop strategies to assay receptor-G-protein interactions and activation kinetics. After moving to Rockefeller University with a Howard Hughes Medical Institute appointment, Tom advanced a series of novel biochemical and biophysical assay platforms, including FTIR and Raman microprobe spectroscopy to study micro-quantities of expressed visual pigment mutants. This work involved active long-term collaborators, including Richard Mathies and Fritz Siebert , and contributed substantially to elucidating the physical chemistry of spectral tuning, and to a better understanding of the molecular mechanism of activation of GPCRs. Many of the conceptual advances that stemmed from this work, such as the concept of “functional micro-domains” and the “helix movement model of receptor activation” were confirmed later when crystal structures became available. Tom’s lab also pioneered the early use of computational homology modeling, molecular dynamics simulations and coarse-grain sampling approaches for membrane proteins in collaborations with Thomas Huber , Xavier Periole , and Siewert-Jan Marrink . Tom’s lab also developed an amber codon suppression method to genetically encode unnatural amino acids into membrane proteins expressed in mammalian cell culture. The genetic code expansion strategy for unnatural amino acid mutagenesis is a key enabling technology for the field and is being used by many laboratories. Early applications included “targeted photo-crosslinking,” and more recently, the parallel development of bioorthogonal labeling strategies to couple fluorophores to expressed receptors and other membrane proteins has allowed the creation of novel sensor constructs and single-molecule detection strategies. Recently, Tom’s lab discovered, along with Yu Chen and Ping Chi , that a mutant of CYSLTR2 is a driver oncogene in uveal melanoma, the most common eye cancer in adults. The CysLTR2 oncoprotein displays biased constitutive activity – it activates Gq/11 but does not undergo β-arrestin-mediated down-regulation. Dr. Thomas P. Sakmar on the web LinkedIn ResearchGate Pubmed ORCHID Google Scholar Rockefeller University Wikipedia Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Scott Struthers R. Scott Struthers, Ph.D., is our co-founder and has served as our President and Chief Executive Officer since December 2008. Prior to Crinetics, he was senior director and head of endocrinology and metabolism at Neurocrine Biosciences, Inc., from 1998 to 2008. At Neurocrine, he initiated and led the effort to discover and develop orally active, nonpeptide GnRH antagonists, including elagolix. Prior to Neurocrine, from 1995 to 1998, he co-founded ScienceMedia Inc. to develop eLearning solutions for the life sciences and higher education markets. Between 1992 to 1995 he led contract research efforts at Biosym Technologies to develop and apply computational tools for drug discovery. In 2021, Dr. Struthers co-founded and serves as board chair at Radionetics Oncology, a pharmaceutical company focused on the discovery and development of novel radiotherapeutics for oncology indications. In addition, he is a member of the board of directors of the San Diego Entrepreneurs Exchange, a nonprofit organization that provides resources for early-stage start-ups, which he co-founded in [2009.] R. Scott Struthers on the web LinkedIn Google Scholar Crinetics Radionetics Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Graeme Milligan About Dr. Graeme Milligan Professor Graeme Milligan is Gardiner Professor of Biochemistry, Dean of Research, and Deputy Head of the College of Medical, Veterinary, and Life Sciences at the University of Glasgow. His main research group centers on the function, structure, and regulation of G protein-coupled receptors (GPCRs) and their interacting proteins. His experience also includes translating knowledge generated into the selection of targets, screening, and identification of small molecule regulators of these proteins, and progressing such ligands in drug development programs. Prof. Milligan has published more than 550 peer-reviewed articles and his research has been cited more than 35,000 times. He was elected to the Fellowship of the Royal Society of Edinburgh in 1998 and to the Fellowship of the Academy of Medical Sciences in 2016. Prof. Milligan is the co-founder of both Caldan Therapeutics (2015) which discovers novel therapeutics for metabolic diseases including Type 2 Diabetes and other indications including non-alcoholic steatohepatitis (NASH) and inflammatory diseases and Keltic Pharma Therapeutics (2020) which is developing new treatments for malaria. Dr. Graeme Milligan on the web University of Glasgow ResearchGate PubMed Orcid Google Scholar LinkedIn Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Ralf Jockers About Dr. Ralf Jockers Ralf Jockers studied in Cologne and received a Ph.D. in biotechnology and biochemistry from the University of Braunschweig, Germany. For postdoctoral training, he joined the laboratory of Dr. Strosberg AD in France, where he worked on the regulation of ß-adrenergic receptors. He is the Research director at INSERM with a specific interest in G protein-coupled receptors by developing original BRET and TR-FRET assays. His laboratory is currently located at the Institute Cochin – Inserm (Paris, France). His laboratory was among the first to demonstrate the oligomerization of GPCRs. He showed the formation of melatonin receptor heteromers in vitro and in vivo and their importance in retinal physiology. He established the concept of ligand-independent functions of orphan receptors in heterodimers with other GPCRs. He discovered multiple rare and loss-of-function variants of the MT2 melatonin receptors that are associated with type 2 diabetes (TD2) development. Many MT2 variants are biased and their defects are signaling pathway-specific opening new perspectives for T2D treatment and precision medicine. His lab was among the first to discover mitochondrial functions of GPCRs. He was the director of the French network of GPCRs (GDR-3545), currently directs the International Research Network (IRN) i-GPCRnet of the CNRS, is chair of IUPHAR « Melatonin receptor » sub-committee, Editor-in-Chief of « Frontiers in Cellular Endocrinology » and AE of « J Pineal Research”. He is a highly cited researcher – 2019 and 2020 identified by Clarivate Web of Science ™. Dr. Ralf Jockers on the web Jockers Lab WGDR-3545 Pubmed Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Jacob Lee and Jin Cho, co-founders of GeneMode, on the ten billion dollars American labs waste every year — and why rebuilding research software from scratch is the most direct path to faster cures. << Back to podcast list Strategic Partner(s) Jacob Lee and Jin Cho: Rebuilding the Software Layer Under Modern Research Most scientific research still runs on infrastructure built for a different century. Spreadsheets lock when two people open them. Freezer inventories live in a senior postdoc's head. An estimated ten billion dollars is spent every year in the United States rebuying reagents already sitting on a shelf nobody could find. In this conversation, Jacob Lee and Jin Cho — co-founders of GeneMode — describe what they saw when they looked at that infrastructure as outsiders and as scientists at once. Lee is a bioengineer whose first year of graduate school was defined by scheduling thirty-minute appointments on a senior postdoc's calendar just to access the lab's inventory software, and that experience is what turned frustration into a company. Cho came from engineering software for military drones at General Atomics, and was stunned when he saw what his friend's lab was paying for a tool that looked straight out of Windows XP. They talk about the slow architecture of drug discovery, the compounding cost of irreproducibility, and why rebuilding the tools scientists use every day is, for them, the most direct path to getting cures to patients faster. About the Guests Jacob Lee is the CEO and co-founder of GeneMode. He trained as a bioengineer and worked as a research scientist in stem cell and cancer labs before founding the company. His frustrations as a first-year graduate student navigating inaccessible lab software became the seed for GeneMode. He leads the company's product vision, focused on inventory, experiment management, and research reproducibility. Jin Cho is the CTO and co-founder of GeneMode. Trained in electrical and computer engineering, he began his career at General Atomics building software for military drones before reuniting with his high-school friend Lee to rebuild research tools from the ground up. At GeneMode he leads the engineering team and the platform's weekly release cycle. Scientific Themes of the Conversation The cost of irreproducibility — waste, delay, and the compounding friction of bad tools Access asymmetry in research — who gets to use the lab's software, and who waits Research software as infrastructure — why tools built for scientists behave differently than tools adapted to them The drug discovery timeline — preclinical, clinical, and regulatory phases, and where software actually matters Collaboration in shared labs — real-time editing, shared freezers, and the Excel-lock problem Lab automation and the hidden operating cost of being a scientist Key Insights from the Conversation Ten billion dollars vanishes every year into duplicate reagent orders. Lee describes an estimate that American labs spend roughly ten billion dollars annually on reagents they already own but can't locate. The cost isn't just money — it's the erosion of reproducibility that follows from not knowing what's in the freezer. Access to the lab's tools is often rationed by seniority. In Lee's first graduate lab, only the principal investigator and a senior postdoc had logins for the expensive inventory software. As a student, he scheduled thirty-minute appointments on a postdoc's calendar to learn how to use a tool the lab had already paid thousands of dollars for. Excel is the default research tool because no one built a better one for scientists. The co-founders argue that most lab software wasn't built for scientists — it was built for general business use and retrofitted. That explains the locked files, the manual re-entry, the outdated look, and the poor fit with how research actually moves. Lab infrastructure is the hidden variable in drug discovery timelines. COVID-era conversations about why vaccines take eighteen months tend to focus on the clinical and regulatory phases. Lee reframes the question toward the preclinical phase, where data management and reproducibility quietly compound every delay downstream. Private and shared workspaces both matter, even in collaborative labs. Cho and Lee describe designing for the reality of shared benchwork: most labs want everything visible to everyone, but individual scientists still need space for protocols-in-progress or personal collections they're not ready to publish internally. Fast release cycles are a signal of infrastructure maturity. Cho describes shipping updates weekly, prioritizing customer-reported bugs and feature requests with a design-to-test-to-ship loop that most scientific software vendors don't attempt. That cadence is itself a philosophical statement about who the tool serves. A ninth-grade English class is an unlikely origin for scientific infrastructure. The GeneMode story starts with two teenagers in the same high-school classroom, different majors, different career paths, and a late-night message asking whether lab software could be hacked together in a weekend. The answer turned out to be no — but the question turned into a company. Episode Timeline Timestamps were generated using AI for readability. 00:00 Summit week welcome and episode introduction 01:34 Meeting the co-founders — CEO Lee and CTO Cho 03:11 From stem cell research to bioengineering frustration 04:03 The ninth-grade English class where the story starts 04:59 Seeing Windows XP-era software inside a modern lab 07:01 What GeneMode actually does that Excel can't 10:15 Onboarding a ten-person lab onto one shared platform 12:18 Ten billion dollars in wasted reagents 16:13 What's coming next — tools across the experimental lifecycle 18:32 Algorithms that predict when reagents will run out 22:43 A weekly release cycle built around user feedback 24:13 Why vaccines still take eighteen months Selected Quotes "A lot of the problems that we're solving is around data sharing for scientists — by having inventory, experiment management, applications, and data all in one collaborative workspace." — Jacob Lee "It looks like software that was built a couple of decades ago. And what surprised me even more was his lab was paying thousands of dollars for this legacy-looking software. I was mind-blown." — Jin Cho "In a lab of ten people, only the principal investigator and a very senior postdoc had access to the software. And as a student, I had to actually schedule times on my postdoc's calendar in thirty-minute segments just to learn how to use that tool." — Jacob Lee "The end goal is really much bigger than helping scientists manage their research projects or inventory. Our mission is to make that research repeatable and reproducible so that we can get those cures faster." — Jacob Lee About this episode In this special episode of the Dr.GPCR podcast , I sat down with the co-founders of Genemod . Jacob Lee and Jin Choe met in ninth grade in English class and have been friends since. Although both went to the same college, Jacob and Jin choose different career paths. One day as they were catching up, Jacob shared his struggles of managing samples and an incredible amount of data and projects in the lab with Jin. Our of this need Genemod was born. Today, Genemod has built a freezer management tool and a project management tool where scientists can manage their reagents, samples, and projects on one intuitive platform. The team is planning on building even more tools that will make Genemod the go-to platform for all research scientists to make research more efficient. Genemode on the web Website Jacob Lee on LinkedIn Jacob Lee on Dr. GPCR Ecosystem Jin Choe on LinkedIn Jin Choe on Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

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

Discover how Dr. Tom Sakmar and Dr. Ilana Kotliar built a multiplexed platform to map GPCR-RAMP interactions and uncover autoantibody-driven GPCR signaling in disease. << Back to podcast list Strategic Partner(s) Hacking GPCRs: Tools, Tech & Drug Discovery with Tom Sakmar & Ilana Kotliar In this episode, host Dr. Yamina Berchiche reconnects with Dr. Tom Sakmar , Professor at Rockefeller University, and Dr. Ilana Kotliar , his former graduate student, to explore the development of powerful multiplex tools designed to map GPCR-RAMP interactions across the receptor superfamily. What began as a focused exploration into Family B GPCRs evolved into a comprehensive resource for the GPCR research community — bridging wet-lab experimentation, open-access tools, and computational biology. A Long-Term Vision Realized “We've done this work for the past 30 years.” – Tom Sakmar Dr. Sakmar recounts how a fateful phone call from Bruce Merrifield decades ago inspired his lifelong focus on Family B GPCRs. That curiosity laid the foundation for a broader investigation into receptor activity-modifying proteins (RAMPs) . The lab’s early partnership with students like Emily Lorenzen catalyzed a transition from single-receptor studies to multiplexed approaches , opening doors to high-throughput interaction mapping. From Curiosity to Collaboration “We decided to evaluate the multiplexing methods... and found this Luminex assay.” – Tom Sakmar After exploring several screening techniques, the lab adopted the Luminex bead-based assay , which allowed simultaneous detection of multiple GPCR-RAMP interactions. This methodology was enhanced through collaboration with Jochen Schwenk’s lab at SciLifeLab in Karolinska. The result: a scalable platform to analyze hundreds of interactions with minimal sample usage. A Rotation That Changed Everything “I really love this project. I want to take it forward.” – Ilana Kotliar Dr. Kotliar joined the Sakmar lab as a rotation student and immediately saw the project’s potential. She expanded the original Family B focus to encompass the entire GPCR superfamily , building a digital and physical toolkit to systematically investigate GPCR-RAMP biology. Her goal was ambitious: map the complete interactome and validate findings in both overexpression and native contexts. Tools for the Community “We have a library on Addgene... dual-epitope tagged GPCRs.” – Ilana Kotliar The team developed two main assets: A web interface to visualize antibody validations and GPCR-RAMP interactions. A DUET-tagged GPCR library (220 constructs) available through Addgene , enabling labs to explore interactions with ease. These tools are fully open to academic researchers , with wide applicability beyond just RAMPs — including scaffold proteins, disease markers, and heterodimerization partners. Driving Impact through Open Science “500+ requests have come in for these clones.” – Tom Sakmar Dr. Sakmar highlights the vital role of Addgene in distributing the DUET library. The logistical lift was considerable — involving extensive 96-well plate work and documentation — but the team prioritized accessibility over proprietary restrictions. Their ethos: empower fellow scientists, not profit from them. Beyond GPCR-RAMP: New Avenues “What if your favorite scaffold protein interacts with GPCRs?” – Tom Sakmar The constructs aren’t limited to RAMP interaction studies. They can be used to probe GPCR associations with any protein , from cytoskeletal scaffolds like 14-3-3 and P11 to disease-linked interactors . The system is modular and adaptable, opening doors for systems biology and context-specific interaction mapping . A Diagnostic Future “Autoantibodies targeting GPCRs might drive disease.” – Tom Sakmar One especially exciting avenue is autoimmune and infectious diseases . The team envisions using these tools to detect GPCR autoantibodies , which are implicated in conditions like long COVID and Graves’ disease . Unlike blocking antibodies, some autoantibodies activate GPCRs , potentially driving pathophysiology — a paradigm-shifting concept in GPCR immunology. From Many to One: De-Orphanization and Precision Focus “You can use this system to de-orphanize receptors.” – Ilana Kotliar While the toolkit enables broad interactome analysis , it’s also valuable for narrowing in on orphan GPCRs — receptors with unknown ligands or function. This could accelerate discovery of therapeutic targets by combining multiplex data with focused downstream assays. In Ilana’s words, it’s a powerful way to “go from many back to one.” The Shift Toward Technology-Driven Biology “Today’s students want to multiplex, miniaturize, and engineer tools.” – Tom Sakmar Dr. Sakmar reflects on the generational shift in research culture. Instead of focusing on a single receptor, students now gravitate toward platforms , biosensors , and data-rich assays . The multiplex strategy aligns perfectly with this evolution, providing scalable approaches to biological discovery. Global Collaboration and Computational Frontiers “There is no science that ends at a national border.” – Tom Sakmar The success of this project hinged on international collaboration and a multidisciplinary mindset . As the field advances, the computational layer — including AlphaFold and structural prediction tools — will play an increasingly pivotal role. This synergy of wet-lab, in silico, and community-driven resources promises a new era for GPCR systems biology . Key Takeaway This episode is more than a conversation — it’s a masterclass in tool-driven discovery , community science, and the future of GPCR interaction mapping . If you’re working on GPCRs, this is your call to leverage these tools , ask new questions, and help unlock previously hidden layers of receptor biology . About Tom Sakmar Tom Sakmar is a physician-scientist and Rockefeller University professor dedicated to drug discovery and chemical biology research, mainly involving GPCRs. He and his artist/designer wife, Karina Åberg, have three teenage children. Tom Sakmar on the web LinkedIn ResearchGate Pubmed ORCID Google Scholar Rockefeller University Wikipedia About Ilana Kotliar Ilana Kotliar is a 5th year graduate student in the lab of Dr. Thomas Sakmar at The Rockefeller University and just recently defended her PhD thesis. Ilana uses chemical biology-based methods to study the regulation and protein-protein interactions of GPCRs. Ilana’s research is multi-disciplinary and involves a close collaboration with the lab of proteomics expert Dr. Jochen Schwenk, located at The Science for Life Laboratory in Sweden. She is a recipient of the prestigious Women in Entrepreneurship Award, an NIH T32 Training Grant, and two Nicholson Fellowships. Outside of the lab, Ilana is a leader within her community, spearheading several outreach initiatives including a global mentoring initiative that matches graduate student mentors to PhD applicants. Ilana graduated Summa cum laude from Cornell University, where she studied Chemistry and Chemical Biology and was recognized as a Merrill Presidential Scholar. Ilana Kotliar on the web Google Scholar LinkedIn Twitter Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Explore Martin Marro’s impact on GPCR drug discovery, assay innovation, and translational pharmacology bridging academia, pharma, and biotech. << Back to podcast list Strategic Partner(s) GPCR Assay Strategy, Bias, and Translational Drug Discovery Scientific Abstract A recurring problem in GPCR drug discovery is that the assay used to find molecules is not always the assay that predicts what those molecules will do in a living system. This conversation follows Martin Marro, head of cell pharmacology in obesity research at Eli Lilly, through more than two decades of confronting that gap across small molecules, peptides, aptamers, and antibodies. Marro describes a Gq coupled receptor program in which four lead series with sub nanomolar calcium potency showed little activity ex vivo and in vivo. Calcium, IP1, and competition binding all failed to predict efficacy. Persisting with an unexplored cAMP hypothesis revealed super agonists with up to threefold greater Emax than the natural ligand, and that readout tracked in vivo efficacy. The discussion extends to biased GLP1 receptor agonists that favor membrane retention and faster recycling, antibody discovery against hard to drug GPCRs, and how the field learned to define biased agonism rigorously. The thread began long before GPCRs: Marro's first research was transgenic wheat in Argentina, aimed at better bread, a quiet nod to a grandfather who was a baker. About Martin Martin Marro is Head of Cell Pharmacology and Executive Director of the Obesity Research Group at Eli Lilly in Boston, where he is building an in vitro pharmacology lab focused on cell based signaling assays for target and drug discovery. He trained at the International Centre for Genetic Engineering and Biotechnology in Trieste, then joined GSK in Stevenage as a Marie Curie Industrial Fellow working on aptamers against chemokine receptors. Over 15 years at Novartis in Horsham and Cambridge, Massachusetts, he led GPCR programs spanning gastrointestinal and cardiovascular metabolic disease, including the discovery of small molecule GLP1 receptor agonist leads and biased fatty acid conjugated GLP1 analogs. At Tectonic Therapeutic, his lab contributed to the discovery of the RXFP1 agonist TX45, and he led the company's first GPCR antagonist antibody program from hit to an optimized lead, later declared a development candidate. Scientific Themes of the Conversation - Why fast, far from equilibrium readouts can mislead lead optimization - Pathway selection, super agonism, and Emax as a driver of in vivo efficacy - Setting a high bar for what counts as true biased agonism - Receptor trafficking, internalization, and recycling as design parameters for GLP1 agonists - Antibodies and aptamers as modalities for difficult GPCR targets - Orphan and class B receptors as enduring challenges in the field Key Insights from the Conversation Potency in the primary assay is not the same as efficacy in the animal Four lead series reached sub nanomolar potency in a calcium assay, yet showed little activity ex vivo and in vivo despite good pharmacokinetic properties. IP1 and competition binding did not close the gap either. The lesson was that a clean screening cascade can still be measuring the wrong thing. Persisting with an unpopular hypothesis rescued a nearly dead program As a junior lab head, Marro proposed pausing the program to examine alternative pathways, biased agonism, and heterodimerization. Management declined because of the program's urgency, so he explored cAMP signaling in the background. The data eventually showed that super agonism in the cAMP assay predicted in vivo efficacy, and the molecule went on to reach the clinic. Maximal response can matter more than potency The molecules that worked were less potent in cAMP than in calcium, which initially made them look like weaker candidates. What set them apart was an Emax up to threefold greater than the natural ligand. That shift in perspective meant accepting a program built on rightward shifted potencies. Calcium is a less specific readout than it looks Calcium can arise from multiple sources, including voltage gated channels, so a calcium signal cannot always be attributed to Gq alone. Longer incubation assays such as IP1 allow readouts closer to equilibrium. Choosing the readout is a scientific decision, not only a throughput decision. Biased agonism deserves a strict definition Around 2007, many Novartis scientists doubted that published examples reflected true ligand bias rather than system bias. An internal GPCR convention set a demanding standard: a reversal in rank order of potency or efficacy between two assays, or a compound inactive in one of them. As tools and analytical methods have matured, the field can now separate these effects more confidently. Keeping GLP1 receptors at the membrane can shape the therapeutic profile Building on work from Stephen Bloom's lab on exendin 4 analogs, Marro's team studied fatty acid conjugated GLP1 agonists that were more biased than semaglutide, with weaker internalization and faster recycling. In diet induced obese mice, the lead matched semaglutide weight loss with less frequent dosing, and no emesis was observed. Moving to a new modality means relearning the flowchart Shifting from small molecules to antibodies required new ways of defining selectivity, assessing biophysical properties early, and treating affinity maturation as the core of hit to lead work. Marro describes it as a genuine learning curve, given how few antibodies against GPCRs exist. Episode Timeline Timestamps were generated using AI for readability. - 00:00 Introduction and building a new obesity research lab in Boston - 02:35 A fellowship discovered the day before the deadline - 07:26 Aptamers, SELEX, and chemokine receptors at GSK - 15:47 Doubting a career choice after a Nobel Prize announcement - 26:16 Sub nanomolar hits that failed in vivo - 32:26 The cAMP hypothesis that resurrected the program - 37:42 Biased GLP1 agonists, trafficking, and weight loss - 44:12 Antibodies against hard to drug GPCRs at Tectonic - 51:03 From green to red: transgenic wheat to GPCR drug discovery - 54:26 Advice for young scientists Selected Quotes "I was intrigued by the fact that a pill that would fit in the palm of your hand could treat symptoms and in some cases cure diseases." Martin Marro "It was inevitable to ask myself whether I had made the right decision. I reflected on the fact that my time in industry was going to come back at some point, and I had to be patient." Martin Marro "My contributions managed to resurrect a project that was almost dead, just trying to think outside the box and persist with my idea." Martin Marro "Most experiments won't work. Most drugs won't make it. The most important thing is not what you face, but how you react to that." Martin Marro Guest Link - LinkedIn: https://www.linkedin.com/in/martinmarro/ Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

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

<< Back to podcast list Strategic Partner(s) Dr. Nicholas Holliday About Dr. Nicholas Holliday After an undergraduate degree at the University of Cambridge, Nick carried out his Ph.D. at King’s College London, supported by an AJ Clark Ph.D. studentship from the British Pharmacological Society. It was these studies and subsequent postdoctoral work that led to Nick's interest in peptide messengers regulating appetite, metabolism, and the immune system, and the molecular mechanisms underlying the signaling and regulation of their GPCRs. Nick joined the University of Nottingham in 2006, where he is now Associate Professor, establishing a lab focused on G protein-coupled receptor kinetics, signaling, and trafficking and on using novel imaging techniques, such as fluorescent ligands and complementation methods, to investigate the underlying mechanisms. Since 2019, Nick has combined his university role with the leadership of Excellerate Bioscience as Chief Scientific Officer, a contract research organization specializing in molecular and cellular pharmacology. Excellerate is involved in several pre-clinical drug discovery projects for both GPCR and non-GPCR targets, using its expertise in pharmacology to deliver high-quality target validation, lead optimization, and mechanism of action studies for our clients. Dr. Nicholas Holliday on the web LinkedIn ORCID University of Nottingham Twitter Excellerate Bio Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Neil Grimsey About Dr. Neil Grimsey " During my postdoctoral studies at USCD, I discovered a novel GPCR-dependent atypical kinase activation mechanism that drives vascular edema and inflammation. These studies shaped my future goals as an Assistant Professor in the College of Pharmacy at the University of Georgia Athens. My group studies the spatiotemporal dynamics of atypical inflammation and the control of disease progression. We have developed an array of fluorescent biosensors to map kinase activity in living cells and are exploring innovative techniques to delineate the molecular dynamics of atypical p38 and suppress kinase activation. To further define the role of atypical p38 signaling responses we are studying how atypical p38 controls the onset and pathogenesis of acute lung injury, retinal vasculopathies, and infections. " Dr. Neil Grimsey on the web LinkedIn University of Georgia Google Scholar X (Twitter) Dr. GPCR Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Stuart Maudsley About Dr. Stuart Maudsley Stuart graduated from the University of Leeds in the U.K. with a First Class Honors degree in Pharmacology. At the end of his studies, he was awarded the Pfizer Prize for undergraduate research. He then completed his Ph.D. at Leeds as well as the University’s Ackroyd, Brotherton, and Brown Scholar. Following his Ph.D., Dr. Maudsley was awarded a Howard Hughes Medical Institute Fellowship to train with Professor Robert Lefkowitz at Duke University. Following this tremendous experience, he was recruited to be the Principal Investigator of the Receptor Biology Section at the Medical Research Council (MRC) -Human Reproductive Sciences Unit within the University of Edinburgh. At the MRC he developed novel prostate cancer therapeutics based upon his research into GPCR pluridimensional signaling. To broaden his biomedical skill-set Stuart next accepted the position of Head of the Receptor Pharmacology Unit at the National Institutes of Health – National Institute on Aging at the Johns Hopkins University Medical Center. At the NIH he was the recipient of the coveted NIH ‘Bench-to-Bedside’ Translational Research Grant Award, one of the few awards available within the intramural NIH program. Upon starting a new family, and returning to Europe, Dr. Maudsley continued his scientific journey with the award of the highly-valued Odysseus Program Type I Program Grant to work as both the Adjunct Director of the VIB Center for Molecular Neurology and also Vice-Chair of the Department of Biomedical Sciences at the University of Antwerp. Stuart’s current research, in the Receptor Biology Lab, focuses on the development of novel GPCR-based therapeutics that interdict diseases based on their gerontological underpinnings. This research stream is now forming the basis of a new technology-based start-up company, HeptOME , to help screen and develop novel longevity/disease-regulating compounds with multidimensional disease efficacy profiles. Dr. Stuart Maudsley on the web Maudsley Lab LinkedIn Google Scholar ResearchGate Maudsley Lab on Facebook Receptor Biology Lab Facebook Group Twitter Semantic Scholar Instagram Neurotree Dimensions Reddit Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Daniel Isom About Dr. Daniel Isom "Dan was born and raised in the Cleveland area. He is a first-generation college graduate and academic. After spending two years at the Cleveland Institute of Art, he earned degrees in Biochemistry and Chemistry from Case Western Reserve University. He then went on to earn a Ph.D. in Molecular Biophysics from Johns Hopkins University, followed by postdocs at both Duke University and UNC Chapel Hill. Dr. Isom was recruited to the Molecular and Cellular Pharmacology Department at the University of Miami Miller School of Medicine in 2016, where he is currently a practicing molecular pharmacologist and biophysicist, systems and synthetic biologist, technologist, heavy CRISPR user, protein sequence- and structure-based informaticist, computational geometer, virtual screener, and Python, medical, and graduate educator leading a talented and multidisciplinary research team. " Dr. Daniel Isom on the web Isom Lab University of Miami Miller School of Medicine LinkedIn X (Twitter) BlueSky Dr. GPCR Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Hay on class B GPCRs, RAMPs, and the selectivity problem in CGRP-targeted migraine therapies - what the approved drugs may still be getting wrong. << Back to podcast list Strategic Partner(s) Debbie Hay: Class B GPCRs, RAMPs, and the Migraine Pharmacology Gap Class B GPCRs represent one of the smaller subfamilies in the GPCR superfamily - just 15 receptor genes - yet they govern a disproportionately wide range of physiology, from calcitonin-mediated bone remodeling to the peptide signaling networks underlying migraine. Their pharmacological complexity is amplified by receptor activity modifying proteins (RAMPs), three single-pass membrane proteins that associate with these receptors to create pharmacologically distinct complexes. A single receptor can form three different functional units depending on which RAMP is present, and those distinctions determine ligand selectivity, signaling output, and ultimately drug targeting. Hay examines the molecular pharmacology of the calcitonin receptor and calcitonin-like receptor - with particular focus on their RAMP-dependent behavior and their roles in CGRP-mediated migraine. She argues that the field has moved faster than the evidence warrants: approving antibodies and small molecules against receptor targets whose full selectivity profile remains uncharacterized. For Hay, who has studied RAMPs since they were first described and when working on them was a high-risk research bet, the CGRP drug approvals are both a vindication and a reminder of how much foundational pharmacology the field skipped on the way to the clinic. ABOUT THE GUEST Hay is a professor of pharmacology at the University of Otago, New Zealand. Her research centers on the molecular pharmacology of class B GPCRs - specifically the calcitonin receptor and calcitonin-like receptor - and their interactions with RAMPs. She has worked across pharmaceutical, biotechnology, and academic settings, including a research placement at GlaxoWellcome, a PhD in molecular pharmacology at Imperial College London, and 17 years at the University of Auckland, where she led her own laboratory and served as head of department. Her current work addresses one of the central unsolved problems in RAMP pharmacology: developing tools selective enough to distinguish between closely related receptor-RAMP complexes in disease-relevant tissues. SCIENTIFIC THEMES OF THE CONVERSATION RAMP-dependent pharmacological diversity in class B GPCRs The selectivity problem in CGRP-targeted migraine therapies Obligatory receptor heterodimers and the limits of current characterization tools Structural biology of RAMPs - allosteric modulation over direct ligand contact Reproducibility and target validation as prerequisites for meaningful GPCR pharmacology Career navigation across academia, big pharma, and biotech KEY INSIGHTS FROM THE CONVERSATION Fifteen Genes, Far More Than Fifteen Pharmacologies Class B GPCRs are a small family by gene count, but RAMP association multiplies their pharmacological diversity considerably. Each of the three RAMPs can pair with a given receptor to produce a distinct complex - different ligand selectivity, different signaling profile, different therapeutic implications. The field routinely treats these complexes as interchangeable, but Hay argues they are not, and that assumption has downstream consequences for how drugs are characterized and how trial failures are interpreted. The Erenumab Selectivity Problem Erenumab, the first monoclonal antibody approved against a GPCR complex, targets the CLR-RAMP1 receptor - the canonical CGRP receptor in migraine. But Hay makes the case that the antibody's selectivity for this complex over the closely related CTR-RAMP1 complex has never been adequately demonstrated. Shared structural features between the two receptor complexes, combined with the known pharmacology of CGRP at CTR-RAMP1, suggest the drug may be less target-selective than its approval label implies - and that effects attributed to one target may partly involve another. mRNA Cannot Tell You Where the Functional Dimer Is For obligatory heterodimers like RAMP-receptor complexes, knowing which component genes are expressed in a cell tells you surprisingly little. The functional unit is the assembled complex at the cell surface, and that assembly is not predictable from transcript data - even at single-cell resolution. Hay frames this as one of the foundational unsolved problems in RAMP pharmacology: without tools to visualize and quantify the actual complex in native tissue under disease conditions, target validation remains incomplete and the pharmacology remains unresolved. RAMPs Act Allosterically - Not Through Direct Ligand Contact Structural data from the CLR and CTR receptor families has produced a result that surprised the field: RAMPs contribute almost no direct molecular contacts to the bound ligand. Their influence on receptor pharmacology appears to be primarily allosteric - subtly reshaping the GPCR binding site rather than contributing their own contact surface. This reframes the design challenge for RAMP-selective compounds: the differences between receptor complexes are conformational and fine-grained, not structurally obvious, making ligand selectivity considerably harder to engineer than a direct-contact model would predict. The Migraine Pharmacology Gap CGRP is elevated in migraine, infused CGRP triggers migraine-like headache in susceptible individuals, and drugs targeting that pathway can abolish chronic migraine entirely for some patients - while doing nothing for others. The mechanistic story remains incomplete: which receptor complex mediates which symptom, why the response is so variable across patients, and what the CGRP system is actually doing in the peripheral and central nervous system. For a condition affecting up to 20% of women worldwide, Hay notes, the research investment in understanding the receptor-level biology is strikingly insufficient. Burning Curiosity as the Non-Negotiable Hay's advice to junior scientists distills to a single criterion: if the curiosity isn't deep enough to outlast the failures, the career won't hold. Grant rejections, papers rejected seven times, experiments that don't replicate - these are not exceptional events but structural features of a scientific life. The scientists who persist, in her framing, are not the ones who feel less pain from those setbacks, but the ones for whom the pull toward the question is stronger than the push of the failure. She gives herself one day to be unhappy about a rejection. Then she moves on. EPISODE TIMELINE Timestamps are AI-generated from the episode transcript and are approximate. Minor offsets may occur in the final edited episode. 00:00 Welcome and episode announcements 01:40 Introduction - Hay 02:43 Career trajectory - from vet school to GPCR pharmacology 07:55 First encounter with GPCRs at GlaxoWellcome - and how RAMPs entered the picture 11:03 Class B GPCRs - why 15 receptor genes produce far greater pharmacological diversity than expected 13:30 CGRP, migraine, and the first antibody approved against a GPCR complex 18:50 Migraine as an invisible disability and the limits of what current treatments explain 20:41 Obligatory dimers and the challenge of mapping receptor complexes in disease-relevant tissue 23:54 Tools the field needs - antibody selectivity, selective ligands, and bimolecular fluorescence complementation in vivo 26:42 Structural data and what it reveals about how RAMPs actually modulate receptor pharmacology 29:43 Are GPCRs still good drug targets - and what is missing from class B pharmacology 31:41 Reproducibility, target validation, and the cost of science that cannot be repeated 34:53 Career advice - burning curiosity, celebrating wins, and being kind SELECTED QUOTES "I can't pick a favorite because these are such complex receptors and we fundamentally don't understand which are most important. Because we don't have selective ligands." "We have to know where our receptor is in our tissue of interest, in our disease condition, and how it is signaling - because that is what we need to target." "There is too much out there that is not replicable. And it causes careers to die. It's just not fair on the junior scientists who then follow up on that work to find it can't be repeated." "If you've got that deep, deep drive still to get over those failures and pick yourself up, and that's a strong enough fire burning, then you will succeed." About this episode Dr. Debbie Hay is presently a professor at the Department of Pharmacology and Toxicology at the University of Otago after spending 18 years at the University of Auckland. Her work is primarily focused on class B GPCRs and their interactions with RAMPs. Debbie obtained a Ph.D. in Molecular Pharmacology from Imperial College London in the UK. She has gained experience from working in academia and at GSK as an industrial trainee. Join me and learn more about Debbie’s career and what she learned through her experiences as a scientist. Dr. Debbie Hay on the web LinkedIn Wikipedia University of Otago University of Auckland Google Scholar Pubmed Research Gate Twitter Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Evi Kostenis About Dr. Evi Kostenis "Pharmacist by training - PhD in Pharmacology - Postdoc at the NIH with Dr. Juergen Wess - Postdoc and Group leader in Aventis, now Sanofi, Frankfurt, Germany - Head of in vitro Pharmacology at 7TM Pharma in Denmark; Full professor, department chair and director of the institute for pharmaceutical Biology at the University of Bonn. Research interests: Signaling mechanisms involving GPCRs and heterotrimeric G proteins" Dr. Evi Kostenis on the web University of Bonn ResearchGate LinkedIn Dr. GPCR Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

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

Bender uses virtual docking to find chemical probes for orphan GPCRs - receptors biology can't study because the tools don't exist yet. << Back to podcast list Strategic Partner(s) Brian Bender: Computational Probes for Orphan GPCR The GPCR superfamily contains hundreds of receptors that cannot be experimentally studied because no usable chemical probe exists for them. Finding an endogenous agonist - when one is even known - is rarely sufficient: a large peptide or lipidated compound may activate a receptor in vivo but is useless as a cell-based tool. This gap is one of the defining bottlenecks in receptor pharmacology, and closing it one receptor at a time will take decades. Brian Bender's work addresses this problem computationally. At UCSF, he develops structural models of GPCRs using sparse experimental data - combining restraints from X-ray crystallography, NMR, and electron paramagnetic resonance spectroscopy - and applies large-scale virtual docking to identify candidate chemical probes across the understudied GPCR landscape. His approach scales across the family rather than stopping at individual targets. Bender trained at the bench before moving fully into computation, and that transition was not planned. A stalled labeling project on the NPY2 receptor during his PhD at Vanderbilt redirected his entire trajectory - and eventually revealed that the patterns connecting receptors across the GPCR family were more interesting than any single structure. ABOUT THE GUEST Bender is a postdoctoral fellow at UCSF working at the intersection of computational structural biology and receptor pharmacology. His research focuses on predicting GPCR structural ensembles from limited experimental data and using virtual docking to identify chemical probes for orphan and understudied receptors. He trained as a structural biologist at Vanderbilt University, working with X-ray crystallography, protein NMR, and electron paramagnetic resonance before transitioning to computation during his PhD work on the NPY2, NPY1, and ghrelin receptors. His fluency in both bench and computational languages shapes how he builds models and how he interprets the experimental data that constrains them. SCIENTIFIC THEMES OF THE CONVERSATION Computational structural modeling of GPCRs from sparse and low-resolution experimental data Virtual docking as a strategy for pan-GPCR chemical probe discovery The orphan receptor problem - why endogenous agonists are not sufficient tool compounds Bench-to-computation transitions and what fluency in both languages enables Family-wide approaches to receptor pharmacology versus single-receptor studies Building scientific community at the early-career stage KEY INSIGHTS FROM THE CONVERSATION The probe gap is a biological bottleneck, not just a chemical one Without a usable chemical probe, a GPCR cannot be studied pharmacologically in a cell-based setting. Even when an endogenous agonist is known, it may be a large peptide or lipidated compound that cannot be practically dosed in vitro. Bender's work targets this gap directly - arguing that de-orphanizing a receptor biochemically and making it experimentally tractable are two separate problems. Virtual docking changes the scale equation Individual bench approaches to identifying tool compounds can take months to years per receptor. Virtual docking screens compress that timeline significantly and can be applied across many receptors in parallel. Bender frames this not as a replacement for bench pharmacology but as the only realistic path to coverage across the full orphan GPCR landscape. The failed experiment that built a career Bender's NPY2 labeling project - designed to generate DEER spectroscopy distance restraints for conformational modeling - never yielded usable data. Rather than a setback, it became a forced pivot into computation at precisely the moment his modeling skills were becoming sufficient to carry a project independently. The stalled experiment was the origin point of the approach he now applies at family scale. Bench experience as a modeling guardrail Knowing what an EC50 means experimentally, or what a Bmax implies about receptor expression, changes how computational restraints are built and applied. Bender credits his time at the bench with preventing the kind of over-interpretation that models built purely from computational intuition can produce - a perspective that shapes how he translates collaborators' data into structural constraints. The eureka of the whole family Months of manually reading sequence alignment tables - before Bender could write the scripts to automate the analysis - produced an unexpected result: structural and sequence patterns connecting receptors across GPCR subfamilies that he had not been told to look for. That period of laborious, close-range data inspection became the conceptual foundation of his pan-GPCR approach, and the moment he understood that one receptor was not enough. Connecting scientists is its own form of science Bender's role co-chairing the Gordon Research Seminar on Molecular Pharmacology is not separate from his scientific work - it is continuous with it. He articulates that the lateral connections formed at early-career conferences, between people who will be colleagues for the next 20 years, are a different kind of scientific output but no less consequential for where the field goes next. EPISODE TIMELINE Timestamps generated with AI assistance and are approximate. They may vary slightly from the final edited version. 00:00 Introduction 01:31 From structural biology to GPCR computation - how the path began 05:47 Modeling GPCR conformational ensembles from sparse data 07:44 Origin moment - a lab notebook at age 8 11:53 The NPY2 labeling project that stalled - and the pivot it forced 17:22 From NPY2 to ghrelin - when one receptor becomes a family question 19:54 Joining UCSF and building the pan-GPCR docking pipeline 21:53 Co-chairing the Gordon Research Seminar on Molecular Pharmacology 47:42 Why orphan receptors need chemical probes, not just endogenous agonists 52:54 Bench fluency as a guard against over-interpreting computational models 58:16 Advice for early-career scientists on connecting with the field 01:02:48 Eureka moment - patterns across the whole receptor family, read by eye SELECTED QUOTES "Are they crazy? Do they know the gold mine that they just gave me?" "It's hard to ever leave the GPCR world once you go into it, just because the longer you stay in it, the more you realize we still don't know in this family." "Taking time to think about what you're doing is way more valuable than just trying to do the next ten million experiments all at once." "I have to go into more receptors. I can't stay with just the one." About Dr. Brian Bender Dr. Bender completed his undergraduate studies at Colgate University in upstate New York with a degree in Biochemistry. Between undergraduate and graduate school Brian worked as a technician in an academic lab before moving to Nashville, TN for graduate work at Vanderbilt University where he joined the Department of Pharmacology. Brain’s work there primarily focused on structure prediction of GPCRs from sparse experimental data. He then moved to the University of California in San Francisco to continue his training as a postdoctoral researcher where he used structural models of GPCRs to virtually screen large compound libraries with the goal of finding new chemical matter to probe understudied and orphan receptors. Brian is involved in organizing the GRC/GRS Molecular Pharmacology meeting, which has been postponed to 2023. Brian is one of the organizers of the upcoming Transatlantic ECI GPCR Symposium . Dr. Brian Bender on the web LinkedIn Twitter ResearchGate Dr.GPCR Member Google Scholar Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Re-cap of Endocrine Metabolic GPCR 2024 with the Organizers About Dr. Aylin Hanyaloglu Dr. Aylin Hanyaloglu has been a Principal Investigator at Imperial College London since 2007. She received her BSc in Human Biology from King’s College London in 1997, and while her Ph.D. commenced at the MRC Human Reproductive Sciences Centre, Edinburgh, a move to Perth, Australia resulted in her Ph.D. in Molecular Endocrinology being awarded in 2002 with Distinction from the University of Western Australia. Dr. Hanyaloglu undertook her postdoctoral training at the University of California, San Francisco with Professor Mark von Zastrow where she identified novel core cellular machinery critical for G protein-coupled receptor trafficking and signaling. Her research focuses on understanding the fundamental cell biological mechanisms regulating GPCR activity, including spatial control of GPCR signaling and receptor crosstalk, and applying these mechanisms for distinct GPCRs in diverse physiological and pathophysiological systems, with particular focus on women's health, pregnancy, and nutrient sensing in the gut. Her work is currently funded by Biotechnology and Biological Sciences Research Council (BBSRC), Diabetes UK, Wellcome Trust, and the Medical Research Council. Dr. Aylin Hanyaloglu on the web LinkedIn Endocrine Metabolic GPCRs Researchgate Twitter Imperial College London Elsevier Loop Dr. GPCR About Dr. Caroline Gorvin "Dr. Caroline Gorvin is a Wellcome Trust & Royal Society Sir Henry Dale Fellow at the Institute of Metabolism and Systems Research, University of Birmingham. She obtained her PhD in 2012 from the University of Oxford, where her research focused on the cellular mechanisms by which mutations in a chloride-proton antiporter cause the renal disorder Dent’s disease. Caroline continued to undertake postdoctoral research in Oxford, investigating the signalling and trafficking of the G protein-coupled receptor (GPCR), calcium-sensing receptor, and its role in calcium homeostasis. Caroline moved to the University of Birmingham in 2018 to establish her research group investigating metabolic GPCRs. Her current research focuses on how metabolic GPCRs cross-talk and interact to regulate appetite and bone metabolism." Dr. Caroline Gorvin on the web University of Birmingham Endocrine Metabolic GPCRs Society of Endocrinology Google Scholar ResearchGate Loop Twitter Dr. GPCR About Dr. Alejandra Tomas "Dr. Alejandra Tomas is a molecular cell biologist and Senior Lecturer at the Department of Metabolism, Digestion and Reproduction, Imperial College London. She obtained a PhD in Biochemistry from University College London and spent several years in Switzerland working on the study of membrane trafficking processes in pancreatic beta cells before returning to the UK, first to her Department at UCL and then to lead a laboratory at Imperial following the receipt of an MRC New Investigator Award in 2015." Dr. Alejandra Tomas on the web Imperial College London Endocrine Metabolic GPCRs ResearchGate Google Scholar LinkedIn Twitter Dr. GPCR Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Mark Connor About Dr. Mark Connor Undergraduate BSc with Honours in Pharmacology from University of Sydney (1987, snake neurotoxins), Ph.D. from Department of Pharmacology, University of Washington (1992, mentor Charley Chavkin , sigma receptors). Postdoc with Graeme Henderson (Bristol, opioids and Ca signaling) and Mac Christie (Sydney, opioids in neurons, novel spider toxins). Grant-funded independent research positions from 2001 at University of Sydney (opioids and sensory neurons), Vollum Institute Portland (visiting scientist with Ed McCleskey, sensory neuron properties); Pain Management Research Institute (more opioids, cannabinoids and T-type Ca channels) and Brain and Mind Research Institute (Sydney). 2009, appointed Professor of Pharmacology at Macquarie University. Focus on study of drugs and toxins on GPCR (opioid, cannabinoid receptor) and ion channel (K, Ca, TRP channel) function; mostly electrophysiology and fluorescence-based reporters, but can grind and bind. Currently pursuing molecular pharmacology of phytocannabinoids and novel synthetic cannabinoids, with a focus on efficacy and novel targets. Interested in orthosteric and allosteric interactions, and still looking for some bias ... anywhere ... these days human only. Dr. Mark Connor on the web Researchers Twitter Google Scholar Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

Career coach Lauren Solano on the skills PhDs undersell, the careers they don't know exist, and the introspection exercise that maps functions to scientific training. << Back to podcast list Strategic Partner(s) Lauren Solano: Mapping Careers Beyond the Bench This episode steps outside the usual GPCR research conversation to examine the career architecture around it. Lauren Solano, CEO and co-founder of Propel Careers, has spent more than a decade coaching PhDs and postdocs and recruiting for biotech and life sciences companies — a vantage point that makes her uncommonly clear about the gap between how scientists describe themselves and how the market reads them. The discussion explores how to translate scientific training into career options that are often invisible to bench scientists, ranging from medical science liaison and clinical research roles to business development, scientific communications, venture capital, and consulting. Solano unpacks the specific transferable skills PhDs consistently undersell — collaboration, leadership, proactive ownership, communicating across technical audiences — and introduces concrete tools for self-assessment and exploration, including the "loved it, loathed it" exercise and a permission-granted approach to informational interviewing. For Solano, the stakes are personal: she didn't know the career she now has was even possible in 2008, which is precisely why she maps the option space for the scientists she coaches today. About the Guest Lauren Solano is CEO and co-founder of Propel Careers, a Boston-based firm that coaches scientists and recruits for biotech and life sciences companies. She trained as a scientist and spent her first decade in preclinical and early clinical drug discovery before pursuing an MBA in 2007 and co-founding Propel in 2009. Her practice centers on helping PhDs and postdocs translate technical training into career paths they often don't realize are open to them. Each year she delivers roughly a hundred talks at universities and research institutions on resumes, negotiation, informational interviewing, and the mechanics of biotech hiring. Scientific Themes of the Conversation The gap between scientific training and the career vocabulary scientists need Transferable skills in the PhD toolkit — and why they go unlisted Informational interviewing as a research method for career planning The limits and real signals of "company culture" in biotech COVID-era shifts in scientist hiring and career reflection Title-function mismatches in life sciences job descriptions Key Insights from the Conversation 1. The "loved it, loathed it" exercise as a career compass Over any given week, note which tasks you enjoyed and which you dreaded. Separate that list from what you're good at — the overlap reveals which career functions, not titles, are worth exploring next. 2. Function over title Job titles in biotech are often creative and inconsistent — a medical science liaison might be called a "clinical information specialist." Scientists navigating a career change are better served mapping careers by tasks and functions first, and treating titles as secondary metadata. 3. PhDs consistently undersell their transferable skills After thousands of conversations with scientists, Solano has found that collaboration, leadership, proactive ownership, and translating technical content across audiences are not universal traits. PhDs tend to have them in unusual concentration — and tend to leave them off their resumes because they assume everyone else has them too. 4. Informational interviews are already permitted Graduate students and postdocs often feel uneasy reaching out to people in other careers, as if the exploration hasn't been earned. Solano reframes this directly: because training ends, career exploration is required, and most people will give fifteen minutes if asked well. 5. "Company culture" is meaningless until you can point at behaviors Every company claims a strong culture. What matters is whether office layout, mentorship practices, and daily behaviors support the claim. The sharper question is what the company does , not what it says. 6. Safety at work is a concrete culture signal Would an employee feel comfortable telling a manager their child is sick, or would they invent another reason? Whether people feel safe at work is a harder measure of culture than any mission statement. 7. Post-pandemic career decisions are about alignment, not just advancement Solano observes that many scientists are using the moment to ask whether their current work matches who they are — not to chase the next rung, but to reset toward impact. Episode Timeline 00:00 Intro and Dr. GPCR Summit preview 01:30 Meet Lauren Solano and Propel Careers 03:11 The path from bench science to career coaching 07:56 Loved it, loathed it — the introspection exercise 10:29 Career options PhDs rarely consider 11:49 Transferable skills scientists undervalue 14:16 The informational interview — permission granted 23:57 The COVID shift in biotech hiring 26:14 Assessing real company culture 31:34 Master resumes and the title trap Timestamps were generated using AI for readability. Selected Quotes "If you had asked me in 2008 if I would be a recruiter slash career coach, I didn't even know that was possible because it hadn't even occurred to me that that is something that would have been a fit." "None of you should be ever worried or afraid or feel awkward reaching out to people for informational interviews because you are supposed to think about your future and learn about different things." "I can tell you in speaking with thousands of PhDs, not everyone is collaborative. Not everyone likes to do novel areas of research. Not everyone is amazing at communicating both to technical audiences and non-technical audiences. So don't undersell your experiences." "Life is frail, right? So if we're not making a difference, if we're not impacting something, why are we doing it?" About this episode In this special Dr. GPCR podcast episode, we sat down to chat with Lauren Celano to talk about career options for Ph.D.’s. Working in a lab allows scientists to gain amazing hard and soft skills, which opens the doors to several great careers that many have not even considered, yet. Lauren has a science background and is passionate about helping talented scientists find their dream position. She is also a speaker, connector, recruiter, and coach. Lauren Celano on the web LinkedIn Propel Careers Email: Lauren@propelcareers.com Dr. GPCR Ecosystem Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

<< Back to podcast list Strategic Partner(s) Dr. Katarina Nemec About Dr. Katarina Nemec " I am a pharmacist with an interest in systems pharmacology and precision medicine. Since my undergraduate studies, I have been engaged in researching molecular mechanisms that govern human (patho-)physiology and their interplay with drugs. I aim to discover new therapeutic approaches, and druggable molecules or refine canonical drug targets to create drugs with fewer adverse effects. I studied Pharmacy at the University in Ljubljana, Slovenia, and at the University of Bonn, Germany, working initially on the role of prostaglandin receptor EP4 in chronic lymphocytic leukemia. During my PhD studies in Martin Lohse lab at the Max Delbrueck Center in Berlin, I consolidated my knowledge of GPCRs pharmacology while performing various cell-based experiments to understand the binding, activation, and signaling of therapeutically relevant GPCRs. In addition, I generated various optical biosensors based on fluorescence or bioluminescence resonance energy transfer technologies (FRET, BRET) that were used for functional screens with state-of-the-art microscopy and high throughput screening to explain novel ways of GPCR modulation. I am continuing with the development of advanced screening approaches in the Madan Babu lab to progress in the understanding of spatiotemporal regulation of biased GPCR activation and signaling. I want to combine experimental approaches with data-driven discovery and adopt data science methodology to tackle relevant scientific questions on the systems pharmacology level. " Dr. Katarina Nemec on the web Babu Lab ResearchGate Google Scholar ORCID LinkedIn Twitter Dr. GPCR Unlock the Full Dr. GPCR Learning Ecosystem ✔ Full Masterclass library ✔ Terry's Pharmacology Corner ✔ Advanced GPCR courses ✔ Scientific discussions → Become Premium Upcoming Live Expert Sessions ➚ 🔒Explore the Full Masterclass ➚ Enjoying the Dr. GPCR Podcast? Leave a Review. Leave a quick review to help more scientists find the show—and help us keep improving every episode. It takes <60 seconds and makes a big difference. ★ Review on Apple Podcasts ★ Rate on Spotify ✉️ Send feedback to the team Thanks for listening to this podcast episode Follow us on your favorite Podcast Player << Previous Podcast Episode Next Podcast Episode >>

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