Highlights of the week Structural insights into prolactin-releasing peptide receptor signaling and G-protein regulated by β-arrestin-1/endothelin axis in human ovarian fibroblasts Methods & Updates in GPCR Research Histamine-modulated wettability switching in G-protein-coupled receptor inspired nanochannel for potential drug screening in membrane receptor signaling pathways and cascade reactions in chondrocytes: a review Is GCR1 the taste receptors . < Previous Next >

Eleonora Comeo synthesizes fluorescent ligands to watch adenosine receptor pharmacology happen in living cells - and explains why targeting these receptors keeps failing. << Back to podcast list Strategic One reason is that selectivity in this family is not just a matter of receptor subtype. in another tissue, because the receptor is already doing something important there. transfected receptor signal from endogenous background.

, odorant receptors, and the trace amine-associated receptors that may one day treat depression. << Back Chemosensory receptors — bitter taste receptors (TAS2Rs), odorant receptors, and trace amine-associated Bitter taste receptors have been identified in the heart and intestine, olfactory receptors in the brain Her group now studies taste receptors, odorant receptors, and trace amine-associated receptors using olfactory system 19:03 Inside a computational workflow for orphan receptors 29:14 Bitter receptors in

Gunnar Schulte of Karolinska Institute makes the case that frizzled receptors are GPCRs — through G-protein The biggest question is how we don't understand how the ligand interacts with the receptor, how the receptor That is my strongest argument for the GPCR nature of these receptors." section Receptor Biology and Signaling at the Department of Physiology and Pharmacology. , the relevance of receptor dynamics, and receptor complex composition for signal initiation and specification

matchmaking - applying recommendation system logic to the bitter taste receptor family Sweet taste receptor receptor inhibitor suppresses the sweetness of heavy water. Taste receptor expression throughout the body reshapes the meaning of drug off-targets Bitter taste receptors properties of both - that can suggest candidate receptors for any new compound. - bitter taste receptors in the airways, gut, heart, and cancer tissues 19:37 - Sweet taste receptors

Pluznick explores what changes when olfactory receptors are treated not as smell receptors but as general-purpose Her lab studies the role of understudied GPCRs — olfactory receptors, taste receptors, and orphan GPRs Reframing olfactory receptors as chemosensors. The name "olfactory receptor" narrows the imagination. Dr. Mice have ~1,000 olfactory receptors; humans have ~350.

and chemokine receptor systems, including CCR2. Receptors in Complexes Behave Differently Than Receptors in Isolation Standard drug screens present a receptor as a discrete, isolated target. In the body, that receptor is complexing with other receptors, scaffold proteins, and cytoskeletal elements receptors are complexing.

Livingston on allosteric opioid modulators, receptor internalization, and navigating the transition from Signaling Beyond the Membrane Opioid receptors belong to a class of GPCRs where the pharmacology extends internalization using live-cell imaging approaches that track receptor dynamics in real time. Internalized receptors don't stop working The membrane-centric view of receptor pharmacology assumes signaling ends when a receptor is endocytosed.

Elva Zhao on biased agonism at the GLP-1 receptor, G protein regulation, and building a mechanistic picture podcast list Strategic Partner(s) Elva Zhao: G Protein Regulation and Biased Signaling at the GLP-1 Receptor The GLP-1 receptor is among the most clinically validated targets in metabolic disease - yet the signaling Her PhD at Western University focused not on receptors but on G protein cycle regulation - RGS proteins Nigel Bennett on biased signaling at the PAR2 receptor, then with Profs.

Nobel laureate Robert Lefkowitz traces the accidental origins of his receptor research — from a Vietnam receptors are discrete molecular entities. Receptors were an unproven concept when Lefkowitz chose to study them When Dr. existence of receptors. There's no such thing as a receptor.

Cheloha builds nanobody-GPCR ligand conjugates that rescue weak peptides, engineer receptor selectivity to podcast list Strategic Partner(s) Ross Cheloha: Nanobody-GPCR Conjugates and the Engineering of Receptor Selectivity The parathyroid hormone receptor sits at the intersection of calcium homeostasis, bone metabolism How does receptor conformation shape the duration of downstream signaling? And can selectivity for one receptor subtype be engineered without redesigning the ligand from scratch

Graciela Piñeyro on what happened when her lab tested biased agonism at the μ-opioid receptor across 25 ligands, why δ-opioid receptors recycle from the lysosome, and the quantitative pharmacology that turned an early artifact into a career of receptor work. << Back to podcast list Strategic Partner(s) Her lab now studies δ- and μ-opioid receptor signaling, biased agonism, receptor trafficking and recycling Long treated as a non-recycling receptor destined for degradation, the δ-opioid receptor can in fact

From chemokine receptors at Rockefeller to founding Dr. GPCR during COVID — the career arc behind the ecosystem built for the field's unreached receptors. << multiple chemokines bind multiple receptors. The 250-receptor problem sits in plain sight. Without that tissue, GPCRs stay siloed by receptor family and by lab.

. << Back to podcast list Strategic Partner(s) Amynah Pradhan: The Delta Opioid Receptor and the Migraine Paradox Chronic migraine sits at a peculiar crossroads in opioid pharmacology: sustained mu opioid receptor For her, this line of work is also personal — the delta opioid receptor has been her scientific focus Paul Clarck , where she studied opioid receptors. Brigitte Kieffer , where she studied ligand-directed signaling at the delta-opioid receptor.

Terry Kenakin on detecting, quantifying, and applying receptor signaling bias in GPCR drug discovery. This phenomenon, receptor signaling bias or functional selectivity, is now recognized as a meaningful It is a consequence of ligand-dependent receptor conformations and allosteric probe dependence, and it The Biology Behind Bias Ligands produce differential pathway engagement at a single receptor because they stabilize distinct receptor conformations.

How receptor residence time — not affinity — rescued a CRF drug discovery program, and why a career in starts with asking what the math never captured. << Back to podcast list Strategic Partner(s) Sam Hoare: Receptor When Sam Hoare and the CRF receptor team at Neurocrin Biosciences discovered that their lead compound sat on the receptor for seven hours while a failed backup fell off in fifteen minutes, it exposed a in vivo stayed on the receptor for seven hours at room temperature.

on orphan GPCR biology, GPCRDB, biased signaling, and how the data analysis bottleneck is reshaping receptor pharmacology and drug discovery. << Back to podcast list Strategic Partner(s) David Gloriam: Orphan Receptors GPCR Pharmacology GPCRs represent the largest and most pharmacologically important family of membrane receptors evolution as a framework for engineering receptor-ligand interactions at the residue level. probes for a range of receptors.

. << Back to podcast list Strategic Partner(s) Brian Arey: Discovering Signaling Bias at the FSH Receptor Biased signaling - the idea that a single receptor can preferentially activate one downstream pathway He is the author of a 2014 book on evolutionarily conserved receptor signaling, co-written with Terry conservation of biased receptor function across receptor classes The physiologist's approach to mechanistic The same logic applies to cytokine receptors, nuclear hormone receptors, and receptor tyrosine kinases

David Hodson on visualizing GLP-1 and GIP receptors in pancreatic islets and brain circuits to advance therapies for diabetes and obesity. << Back to podcast list Strategic Partner(s) Visualizing GLP-1 & GIP Receptors in Islets and Brain In this episode, Professor David Hodson discusses how GLP-1 and GIP receptors regulate metabolism across the pancreas and brain, and why visualizing receptor localization and signaling in Why this matters How receptor distribution in islets and brain circuits shapes incretin hormone drug

John Streicher: Reorganizing Opioid Signaling Beyond the Receptor The dominant strategy for improving opioid therapy has been to engineer new ligands at the receptor itself — biased agonists, partial agonists In the brain, HSP90 promotes ERK activation downstream of the mu opioid receptor and is required for Receptor signaling assays showed efficacy shifts in the spinal cord and tolerance attenuation in the John Streicher 01:49 From heart failure to opioids — a path through signaling 07:49 Why the mu receptor

He describes the purification and cloning of the CGRP receptor, the identification of receptor activity-modifying proteins (RAMPs), and the realization that CGRP signaling required receptor complexes rather than a of peptide receptor activation and made clear that receptor complexes, not single proteins, could underlie Deorphanizing Receptors Blends Bioinformatics and Bench Work . Dr. Target Validation Is Harder Than Cloning a Receptor .

and the challenges of discovering ligands for understudied receptors like the galanin receptor family and the galanin receptor family. This illustrates how receptor pharmacology often involves complex, receptor-specific effects. 5. My favorite GPCR is not the opioid receptors. Instead, it’s the galanin receptor . Dr. There are three members of the galanin receptor family: galanin receptor 1, 2, and 3.

These are questions you cannot answer in a HEK cell overexpressing a receptor it was never meant to see Working on chemokine receptor CCR1 in multiple myeloma, free fatty acid receptor FFA2 in type 2 diabetes acid receptor FFA2 in type 2 diabetes, and muscarinic M2 and M3 receptors, consistently prioritizing as a property of a compound and a receptor. receptor.

Bender uses virtual docking to find chemical probes for orphan GPCRs - receptors biology can't study Partner(s) Brian Bender: Computational Probes for Orphan GPCR The GPCR superfamily contains hundreds of receptors when one is even known - is rarely sufficient: a large peptide or lipidated compound may activate a receptor This gap is one of the defining bottlenecks in receptor pharmacology, and closing it one receptor at "I have to go into more receptors. I can't stay with just the one." About Dr. Brian Bender Dr.

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 Hay examines the molecular pharmacology of the calcitonin receptor and calcitonin-like receptor - with and calcitonin-like receptor - and their interactions with RAMPs. - the canonical CGRP receptor in migraine.

Specifically, I am interested in understanding dysregulated G-protein coupled receptor (GPCR) signaling During my post-doctoral research, I was part of a study that identified the receptors of a novel human In this study, I discovered adrenergic receptors (α2A, α2B, and β2-adrenergic receptors) that serve as the gut microbial metabolite (PAG) receptor and characterized the receptor-metabolite interaction. My long-term plan is to conduct research in the field of receptor biology, with a focus on GPCRs.

Structural biologist Qing Fan describes a decade of GABA-B receptor research at Columbia - from obligate glutamate receptors, and the calcium-sensing receptor, the molecular mechanisms governing their activation forming in an FSH receptor crystal that she could not set aside. critical component of the receptor's inactive state. A decade on one receptor: the cost and the clarity it produces Fan has worked on the GABA-B receptor

These hybrid receptors enable researchers to probe receptor signaling, investigate G protein coupling receptors with poorly understood receptors. A hybrid GPCR is a receptor constructed by combining elements from two different receptors. Some receptor combinations work very well, while others fail—even when the receptors are very similar Some papers call them hybrid receptors, others call them chimeric receptors, and sometimes they’re just

studying GPCRs in HEK293 cells misses critical biology — and how iPSC-derived models and intracellular receptor Hebert's research focuses on the angiotensin AT1 receptor, a signaling hub coupled to Gq, Gi, G12, and Intracellular GPCRs as Drug Targets — Receptors on the nuclear and mitochondrial membranes represent The AT1 Receptor Defies Simple Classification The angiotensin AT1 receptor is not just a Gq-coupled receptor A Clinical Trial Failure That Pointed Forward The Trevena biased agonist for the AT1 receptor failed

Paul Insel explains how unbiased GPCR expression profiling uncovered overlooked receptors in cancer — purinergic receptors and, most recently, proton-sensing GPCRs in the tumor microenvironment. The field's reductionism may be hiding how receptors actually work Dr. And the answer was PAR1, the thrombin receptor. From that point on, Paul was hooked and has since studied receptor function in human physiology, receptor