John Streicher: Reorganizing Opioid Signaling Beyond the Receptor The dominant strategy for improving His team treats opioid signaling as a problem of circuit organization: the same kinases and second messengers therapeutic index, signal organization downstream of opioid receptors, and the unexpected effects of Scientific Themes of the Conversation Opioid signaling specificity as a problem of circuit organization John Streicher 01:49 From heart failure to opioids — a path through signaling 07:49 Why the mu receptor

Her research integrates behavioral pharmacology, ligand-directed signaling, and mouse models of migraine as fundamentally altered biological systems — and what that means for drug discovery Ligand-directed signaling Paul Clarck , where she studied opioid receptors. Brigitte Kieffer , where she studied ligand-directed signaling at the delta-opioid receptor. Amynah studied how arrestins regulate ligand-directed signaling at delta-opioid receptors, and it is

Modulators and Receptor Signaling Beyond the Membrane Opioid receptors belong to a class of GPCRs where Rather than measuring endpoint states, she learned to watch receptors move, internalize, and continue signaling , and therapeutic rationale Receptor internalization and post-endocytic signaling as a paradigm shift Von Zastrow's lab challenged this directly, demonstrating that GPCRs continue to generate signals after A readout that captures a downstream marker, a surrogate signal, or a population average can yield clean

If the right ligand could engage G-protein signaling while sparing β-arrestin, pain relief might finally Her lab now studies δ- and μ-opioid receptor signaling, biased agonism, receptor trafficking and recycling Even as the field pushes toward iPSC-derived somatic systems, HEK-cell signaling profiles of μ-opioid Graciela has done extensive work on the molecular pharmacology of opioid receptors, exploring their signaling , trafficking, and their ability to activate different signaling pathways and signaling bias.

to visualize receptor-ligand interactions and uncover the molecular mechanisms underlying receptor signaling Kim’s research focuses on druggable membrane proteins, particularly GPCRs involved in neurological signaling protein biochemistry, and pharmacological insights to better understand how ligands modulate receptor signaling :00 — The scientific appeal of membrane proteins How membrane proteins serve as the entry point for signaling “Membrane proteins are where signaling begins—the moment a molecule tells the cell what to do.”

Postdoc with Graeme Henderson (Bristol, opioids and Ca signaling) and Mac Christie (Sydney, opioids in Grant-funded independent research positions from 2001 at University of Sydney (opioids and sensory neurons visiting scientist with Ed McCleskey, sensory neuron properties); Pain Management Research Institute (more opioids Focus on study of drugs and toxins on GPCR (opioid, cannabinoid receptor) and ion channel (K, Ca, TRP

Catherine Demery shares how she found clarity and purpose in academic opioid research. Fentanyl and xylazine are pushing the opioid crisis into dangerous new territory, and Catherine Demery Her research combines cutting-edge GPCR signaling studies with real-time public health data from Michigan Why This Matters Fentanyl : Potent synthetic opioid that decreases inhalation rate. Why xylazine is an emerging overdose threat and how it differs mechanistically from opioids.

Bet on a Non-Psychedelic Psychedelic Psilocybin is in Phase 3 trials for depression, and the early signal This raises one of the most consequential questions in current GPCR pharmacology: can biased signaling His lab works on serotonin, dopamine, and opioid receptor structure, function, and drug discovery, with Roth's lab identified salvinorin A as a kappa opioid receptor agonist. :00 The visiting professor's lecture that sealed it: receptors 06:30 When the field debated whether opioid

pain pathway What it means to “teach AI protein dynamics,” and how Superluminal is using it to predict signaling /PhD, a rejection letter pivoted him into a PhD program at the University of Iowa, where he studied opioid Driven by the opioid crisis and the lack of non-addictive pain treatments, Ajay co-founded Blue Therapeutics company using machine learning to explore GPCR structure-function relationships and predict biased signaling

GPCR scientist Ben Clements shares how positive allosteric modulators could transform opioid therapy GPCRs and the Opioid Crisis: A New Pharmacological Frontier Now at the University of Michigan, Ben focuses on positive allosteric modulators (PAMs) targeting opioid receptors. “We’re enhancing the powerful pain-relieving effects of opioids while limiting respiratory depression uses in vitro and in vivo models to discover and characterize novel treatments for chronic pain and opioid

The human genome encodes more than 800 GPCRs — and just two beta-arrestin isoforms to regulate their signaling open questions: how do just two beta-arrestin isoforms, structurally nearly identical, mediate the signaling Shukla's lab and others have shown they signal robustly through beta-arrestins — which makes them, in signaling that drove early opioid receptor drug design has not held up cleanly in subsequent studies Jawaharlal Nehru University in India and it was during a biochemistry class where he learned about cell signaling

These ligands stimulate receptor β-arrestin recruitment without activating canonical G protein signaling Because BAMs engage less well-conserved allosteric sites and exert pathway-specific effects on receptor signaling , they are exciting tools for linking distinct signaling pathways with their physiological effects and selectivity can be leveraged in the development of safe and effective treatments for stimulant and opioid

He has been also studying what aspects of GPCR signaling are regulated in a sex-selective manner and Thomas Sakmar’s laboratory at The Rockefeller University, where she study’s the signaling and degradation She is currently working to understand the signaling and degradation of GPCRs in disease states to help lab where she helped to investigate the role of various ATP-sensitive potassium channels in pain and opioid

transmembrane domain connect to Rett syndrome and epileptic encephalopathy, and what allosteric and biased signaling what pathway-selective drug design can achieve: a compound that confers analgesia through G protein signaling structures as a path toward precision medicine 19:03 - GPCRs as drug targets: allosteric sites, biased signaling "Ligands that display biased signaling property may serve as highly specific drug candidates. structural biologist interested in the molecular mechanisms controlling how class C GPCRs transmit signals

These ligands stimulate receptor β-arrestin recruitment without activating canonical G protein signaling Because BAMs engage less well-conserved allosteric sites and exert pathway-specific effects on receptor signaling , they are exciting tools for linking distinct signaling pathways with their physiological effects and selectivity can be leveraged in the development of safe and effective treatments for stimulant and opioid

"I wasn't able to get stronger pain meds because of the opioid epidemic," he recalls. Serafini found himself repeatedly drawn to them, or more precisely, to RGS (Regulators of G protein Signaling him to BSL-3 labs to study persistent pain after SARS-CoV-2 infection, revealing novel immune-neuron signaling

Graciela Pineyro — a principal investigator at CHU Sainte-Justine in Montreal studying GPCR signaling a principal investigator at CHU Sainte-Justine in Montreal, where her research group works on GPCR signaling She has done extensive work on the molecular pharmacology of opioid receptors and is currently focusing

Whether you’re decoding signaling pathways or designing the next generation of therapeutics, Revvity it doesn't emit a strong signal when bound to the surface. TRF detection, which effectively filters out short-lived background signals. pathway, from ligand binding and G-protein activation to intracellular signaling readouts. All four formats are validated in well-established models like GLP1R and Mu opioid receptor (MOR), and

antibody failures during knockout mouse experiments - purchasing commercial antibodies that produced signal researcher approached the GeneTex booth and described his situation: he had knockout mice for the mu opioid receptor, purchased multiple commercial antibodies, and found that several of them produced signal in

Terry Kenakin ’s hands-on workshop, The Practical Assessment of Signaling Bias . Didn’t sign up? Highlights of the Week How Ligands Achieve Biased Signaling toward Arrestins Stéphanie Gaillard , Neha obesity drug discovery: Cell-based assays for GLP-1 and the G-Suite March 17 - 21, 2025 | 2nd GPCR signaling Principal Scientist, Medicinal Chemistry PhD fellowship in GPCR mechanosensing GPCR Activation and Signaling g , MC4R , docking , opioid , peptide ligand design , protein design , Ca2+ oscillation , GPCRs , basal

. << Back to podcast list Strategic Partner(s) How Lipid Rafts Organize GPCR Signaling Scientific Abstract Sedaghat discusses the compartmentalization of GPCR signaling in lipid rafts, including work linking to the classical paradigm of GPCR phosphorylation and desensitization - Compartmentalization of GPCR signaling Where a receptor sits shapes what it signals Lipid rafts can segregate signaling proteins from their There are exceptions in every step of GPCR signaling."

Michelle Halls reveals how organized GPCR signaling drives assay innovation and new therapeutic insights . << Back to podcast list Strategic Partner(s) Leadership, Impact, and GPCR Signaling with Dr. Michelle Halls shares how dissecting the spatial organization of GPCR signaling opens new doors in drug From early discoveries in cyclic AMP signaling to uncovering ultrasensitive receptor responses at femtomolar localized signaling events, how these mechanisms are hijacked in disease, and how they can be leveraged

How a bell-shaped FSH dose-response curve led to one of the earliest demonstrations of biased GPCR signaling Bias at the FSH Receptor Biased signaling - the idea that a single receptor can preferentially activate at the FSH receptor, which were among the first experimental demonstrations that a GPCR could signal Arey treated it as a signal. His recently published book on signaling bias, Biased Signaling in Physiology, Pharmacology, and Therapeutics

list Strategic Partner(s) Jennifer Pluznick: Olfactory Receptors in the Kidney and the Gut-Microbe Signal Gut microbes at the other end of the signal. Matsunami's RTP1S chaperone, the Rho tag, and the Pluznick lab's Lucy tag — a cleavable leucine-rich signal

changes that propagate from ligand-binding sites to intracellular signaling partners. Understanding how ligand binding leads to specific signaling outcomes—particularly ligand bias toward Nivedha describes how allosteric signaling within receptors can be quantified at atomic resolution. Allosteric Communication Explains Signal Propagation Ligand binding does not directly trigger signaling She uses molecular dynamics and network analysis to map signaling pathways through receptors.

GPCRs Do Not Produce a Single Signal Dr. Activation of a receptor can generate multiple signaling pathways, and different ligands can bias signaling Absence of a Signal Can Be a Discovery One of Dr. “People think a receptor produces one signal. In reality, a receptor produces many signals.” But GPCRs activate multiple signaling pathways simultaneously.

<< Back to podcast list Strategic Partner(s) Developing new tools to uncover GPCR signaling patterns works on diverse models and diseases, and has developed a wide array of tools to dissect GPCR/G protein signaling

Discover how GPR65 reshapes our understanding of GPCR signaling and its role in cancer, with Dr. GPCR podcast. << Back to podcast list Strategic Partner(s) Signals, pH, and Discovery : Cracking GPCR This dual functionality—environmental sensing and compartment-specific signaling—offers a new layer of reflects on the value of a supportive lab culture , the need for better experimental tools in GPCR signaling My research has looked at the trafficking and signaling of adrenergic and proton-sensing receptors, with

Paul Insel turned dry-lab science into a reframing of COVID-19 pathobiology as a GPCR signaling imbalance Back to podcast list Strategic Partner(s) Paul Insel: Rethinking COVID-19 Pathobiology Through GPCR Signaling What came next was a series of papers reframing severe COVID-19 as a disease of signaling imbalance: His research career has centered on GPCR signaling — with particularly deep work on beta-adrenergic receptors Severe COVID-19 may be a story of signaling imbalance, not just viral damage.

Terry Kenakin on detecting, quantifying, and applying receptor signaling bias in GPCR drug discovery. into a practical decision-making tool in GPCR drug discovery Beyond Potency: What Ligand-Dependent Signaling Reveals About Drug Candidates G protein-coupled receptors can signal through multiple intracellular This phenomenon, receptor signaling bias or functional selectivity, is now recognized as a meaningful This webinar explains the biological basis of signaling bias, shows how to detect and quantify it using