Dr. GPCR Podcast

Dr. Yamina Berchiche

We bring you closer to dedicated scientists who work tirelessly to help understand GPCR pathophysiology.

  1. MAR 18

    Can Simulations Predict GPCR Ligand Bias?

    How does ligand binding at the extracellular pocket of a GPCR reshape signaling on the intracellular side? Biased agonism is often measured through pathway activation assays, but the structural origin of ligand bias remains difficult to trace. Can molecular simulations reveal the communication routes that link ligand binding to G protein or arrestin signaling? In this conversation, computational biologist Anita Niveda explores how molecular dynamics and network analysis can map allosteric communication within GPCRs—revealing how microscopic structural pathways relate to macroscopic signaling outcomes. From discovering bioinformatics as an undergraduate to developing computational methods for quantifying ligand bias, the discussion moves through the scientific thinking behind modeling receptor signaling, collaborations between academia and industry, and how computational tools are becoming predictive instruments in drug discovery. Key Topics in This Episode How molecular dynamics simulations reveal communication pathways connecting ligand binding sites to G protein or arrestin interfaces Why mapping allosteric communication networks helps explain biased agonism in GPCR signaling What computational strategies can quantify ligand bias directly from receptor structures How receptor subtype selectivity emerges from subtle structural and dynamic differences in binding pockets Why academic–industry collaborations can accelerate method development in receptor pharmacology What career decisions shape the path from computational biology training to drug discovery roles Timestamps 0:00 A structural question behind ligand bias1:30 Introduction and scientific background3:40 Discovering bioinformatics and computational biology7:30 First encounters with GPCR structural biology9:40 Finding and choosing a postdoctoral lab16:40 Entering GPCR research and allosteric communication18:20 Quantifying ligand bias using simulations20:00 Mapping signaling pathways through receptor residues23:30 Academic–industry collaboration with Boehringer Ingelheim27:00 Moving from academia to industry research35:00 Interviewing and transitioning into biotech45:00 Aha moments in computational GPCR research50:00 The diversity of GPCR families and signaling biology Keywords: GPCR podcast, GPCR signaling, biased agonism, drug discovery, receptor pharmacology

    55 min
  2. Why Mosquitoes Hunt You: The GPCR Behind the Bite

    MAR 4

    Why Mosquitoes Hunt You: The GPCR Behind the Bite

    Conserved neuropeptide Y GPCRs orchestrate both feeding and mating behaviors in mosquitoes, with direct translational parallels to human gut-brain signaling. Quick Summary Learn how receptor internalization and neuropeptide GPCR signaling underlie the regulation of mosquito host-seeking and reproduction. Dr. Laura Duvall details the use of CRISPR-based assay development and fluorescence-driven phenotyping to connect molecular manipulation to whole-animal behavior. Her approach provides actionable insights for gpcr drug discovery and tools to dissect homologous pathways across model systems, with implications for pharmacology research targeting vector-borne disease transmission. Key Takeaways Neuropeptide Y GPCRs modulate both host attraction and mating in Aedes aegypti. CRISPR and fluorescence assays enable precise behavioral phenotyping in vivo. GPCR-targeted compounds designed for humans can modulate mosquito receptors. NPY receptor expression in mosquito gut mirrors mammalian gut-brain signaling axes. Automated behavioral assays combined with machine learning sharpen data resolution and reduce human bias. Dr. GPCR Links & Resources Explore essential resources: Dr. GPCR Ecosystem Membership & Pricing Weekly News Advance your research—discover the power of Dr. GPCR Premium. About the Guest Dr. Laura Duvall earned her B.A. in Biochemistry and Biological Basis of Behavior from the University of Pennsylvania, followed by a PhD at Washington University in St. Louis, where she explored neuropeptide regulation of circadian behavior in Drosophila. Transitioning from fruit flies to mosquitoes, she pursued postdoctoral research at Rockefeller University with Leslie Vosshall, focusing on the molecular regulation of feeding and mating behaviors in Aedes aegypti. In 2019, she established her independent laboratory at Columbia University's Department of Biological Sciences and the Zuckerman Institute. Dr. Duvall’s work is recognized by awards including the Beckman Young Investigator Award, Klingenstein-Simons Fellowship in Neuroscience, and the Pew Scholars Program, reflecting her drive to unravel the complex signaling mechanisms that govern mosquito and broader animal behavior. Guest on The Web LinkedIn: https://www.linkedin.com/in/laura-duvall-28a03485/ Google Scholar: https://scholar.google.com/citations?user=Vk3KGSoAAAAJ&hl=en Lab: https://www.duvalllab.com/

    51 min
  3. FEB 18

    GPCR Location and Lipid Raft Signaling

    Key Takeaways How does the precise localization of GPCRs in lipid rafts reshape drug discovery strategy? Examine implications for functional assays and therapeutic innovation. Explore the pivotal role of GPCR-lipid raft compartmentalization in receptor signaling, desensitization, and pharmacology research. Dr. Keyvan Sedaghat discusses assay approaches, regulatory mechanisms, and the translational impact of bitter taste receptors beyond sensory biology. Leveraging decades of experience in assay development and database creation, he offers actionable insights for researchers optimizing GPCR drug discovery pipelines. Compartmentalization of GPCRs in lipid rafts directly influences receptor signaling and drug response. Desensitization pathways of dopamine D1 receptors depend on precise phosphorylation domains—challenging classical paradigms. Bitter taste receptors demonstrate functional relevance in non-gustatory tissues with emerging therapeutic applications. Database-driven research accelerates the identification of receptor-microdomain interactions for novel targets. Integration of computational modeling and biochemical validation is essential for advancing GPCR assay strategies. Dr. GPCR Links & Resources Access the Dr. GPCR Ecosystem at https://www.ecosystem.drgpcr.com/ for community, tools, and databases. Details on Membership & Pricing: https://www.ecosystem.drgpcr.com/university-pricing GPCR Weekly News: https://www.ecosystem.drgpcr.com/gpcr-weekly-news Explore Dr. GPCR Premium for expanded translational resources and networking. About the Guest Dr. Keyvan Sedaghat holds a pharmacy degree and a PhD in cellular and molecular medicine, specializing in pharmacology, from the University of Ottawa. With over two decades of academic experience, he has served as a professor, senior lecturer, and chief scientific officer in the pharmaceutical and cosmetic industries. Dr. Sedaghat’s work spans peer-reviewed publications and editorial roles across journals in molecular pharmacology, cell signaling, and G protein-coupled receptors. His scientific drive centers on unraveling molecular mechanisms underlying GPCR function and translating those findings into effective teaching, research, and drug discovery strategies. Guest on the Web: LinkedIn Google Scholar

    37 min
  4. FEB 4

    Choosing the Right GPCR Assays for Translational Drug Discovery 180

    Episode Summary Potent in vitro hits often fail in vivo—Martin Marro details how robust assay choice and pathway deconvolution can revive GPCR drug discovery programs. Listeners will learn practical approaches to assay development for GPCR drug discovery, the pitfalls of calcium readouts, and how identifying pathway bias impacts translational success. Dr. Marro shares his experience bridging in vitro–in vivo gaps, refining selection flowcharts, and leveraging pharmacology research to drive clinical candidates. His strategic perspective is rooted in years of leading multimodal discovery teams in pharma and biotech. Key Takeaways Assay selection critically shapes the trajectory from hit to clinic.Calcium and IP1 assays may not predict in vivo efficacy for all Gq-coupled receptor targetsAlternative pathway analysis may be essential for mechanism elucidation.Persistence in probing beyond standard readouts can rescue high-profile discovery programs. Team structure and collaborative problem-solving are pivotal in resolving translational bottlenecks. Explore Dr. GPCR Resources - Dr. GPCR Ecosystem - Membership & Pricing - Weekly News Explore the full depth of GPCR resources, events, and member-exclusive tools with Dr. GPCR Premium. About the Guest Dr. Martin Marro leads the Cell Pharmacology group in the DOCTA division at Lilly’s Seaport Innovation Center in Boston, MA. Trained as a pharmacologist, Dr. Marro has accumulated over 20 years of experience spanning large pharmaceutical firms—including GSK, Novartis, and Lilly—and innovative biotech such as Tectonic Therapeutic. He holds deep expertise in early drug discovery across small molecules, peptides, and antibody therapeutics for metabolic, cardiovascular, and gastrointestinal diseases. Dr. Marro’s research has been central to the discovery and characterization of multiple clinical candidates, with a focus on GPCR target validation, receptor pharmacology, and translational assay strategies. He played a key role in patenting and developing novel fatty acid-conjugated GLP-1 receptor agonists. Driven by the challenge of translating robust in vitro science into clinical proof-of-concept, Dr. Marro’s leadership continues to impact the field of GPCR drug discovery. Keywords: gpcr podcast, assay development, pharmacology research.

    51 min
  5. 12/03/2025

    Imaging GPCRs in Action: Chemical Probes for Next-Level Discovery | Dr. Johannes Broichhagen #178

    Chemical probes are reshaping how we map GLP-1R in real time — revealing receptor pools antibodies can’t reliably capture. This is Episode 2 of a 3-part GPCR tool-development series created in partnership with Celtarys Research. Summary: Dr. Johannes Broichhagen aka JB breaks down the design logic behind fluorophore-linked peptides, assay trade-offs, and what true receptor internalization looks like in live tissue. A concise masterclass in assay development and GPCR drug discovery. What you’ll learn: • Why antibody variability pushed JB toward chemical probe engineering • The design logic behind Luxendin-based fluorescent tools — and how structure guides function • What “good assay development” looks like when cells, tissue, and probe behavior collide • Behind-the-scenes stories from the collaboration with David Hodson • Why parallelized experiments matter for reproducibility and signal quality • How small-molecule probes outperform antibodies in live-cell and tissue imaging • The surprising breakthroughs that shifted JB’s entire research trajectory • Future directions: multi-color GPCR mapping, AI-guided ligand design, and in vivo chemical biology Dr GPCR Links & Resources: • Dr. GPCR Ecosystem: https://www.ecosystem.drgpcr.com/ • Membership & Pricing: https://www.ecosystem.drgpcr.com/university-pricing• Weekly News: https://www.ecosystem.drgpcr.com/gpcr-weekly-news

    39 min

Ratings & Reviews

4.8
out of 5
12 Ratings

About

We bring you closer to dedicated scientists who work tirelessly to help understand GPCR pathophysiology.

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