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August 2022 Dopamine D 1 receptor-mediated β-arrestin signaling: Insight from pharmacology, biology, A major pan-receptor focus has been to identify GPCR-selective ligands that have bias in G protein-dependent the past two decades, it is only recently that highly β-arrestin biased ligands for the dopamine D1 receptor

tools—especially AlphaFold —are helping crack the mystery of olfactory GPCRs , one of the most elusive receptor The Problem: Hundreds of Receptors, Almost No Ligands Alessandro’s work focuses on olfactory GPCRs—nearly 400 distinct receptors that play key roles in smell but remain largely uncharacterized . Enter AlphaFold: Predicting the “Face” of a Receptor When Alessandro began his PhD, structural models From Prediction to Discovery One of Alessandro’s projects focused on receptor R5VK1 , where his team

Allostery isn’t just an advanced concept—it’s essential to understanding efficacy, ligand bias, and receptor Map dynamic receptor behavior to real-time decision-making.  

September 2022 "The glucagon-like peptide-1 receptor (GLP-1R) plays a key role in metabolism and is an

September 2022 Structure of the human galanin receptor 2 bound to galanin and Gq reveals the basis of Three G-protein coupled receptors (GPCRs) for galanin have been discovered, which is the focus of efforts To understand the basis of the ligand preferences of the receptors and to assist structure-based drug

September 2022 Cell Surface Calcium-Sensing Receptor Heterodimers: Mutant Gene Dosage Affects Ca 2+ Sensing but Not G Protein Interaction "The calcium-sensing receptor is a homodimeric class C G protein-coupled receptor (GPCR) that senses extracellular Ca2+ (Ca2+o ) via a dimeric extracellular Venus flytrap (VFT severe hyperparathyroidism (NSHPT), receptor function was markedly impaired. We consider how receptor asymmetry may support the underlying mechanisms. © 2022 The Authors.

Mutations in G protein-coupled receptors (GPCRs) underlie numerous diseases. Many cause receptor misfolding and failure to reach the cell surface. We previously demonstrated rescue of cell surface expression of luteinizing hormone receptor mutants we demonstrate that a similar approach can be employed to rescue mutant follicle-stimulating hormone receptors

why two drugs with similar affinity may behave completely differently , and how the secret lies in receptor In this session, you’ll gain: ✅ A deeper understanding of how every ligand alters receptor conformation—and Ligands don’t just “bind”—they change  the receptor. These changes can alter how the receptor talks to G proteins, arrestins, or other receptors. receptors, where ligand context fundamentally changes modulator behavior.

August 2022 "Abstract Sigma receptor is a transmembrane non-GPCR protein expressed mainly in the endoplasmic

Bitter taste receptors (TAS2Rs) are a poorly understood subgroup of G protein-coupled receptors (GPCRs The experimental structure of these receptors has yet to be determined, and key-residues controlling

The company’s scientific approach relied on targeting GPCRs — specifically opioid receptors — using biased The company’s goal is to model receptor dynamics — including biased signaling — to predict drug behavior Superluminal is building systems that learn from receptor movement, conformational shifts, and complex By making receptor behavior computationally predictable, Ajay and his team are working to reduce the

Alterations in the expression and/or activity of brain G-protein-coupled receptors (GPCRs) such as dopamine functional role of kurarinone, an abundant lavandulated flavonoid in Sophora flavescens, on dopamine receptor

In this sense, G protein-coupled receptors (GPCRs) may be a good option to try to prolong our life while

Crystal structures suggest ligand access to the orthosteric binding site of MT1 and MT2 receptors through entry route for 2-iodomelatonin, a nonselective agonist with a slower dissociation rate from the MT2 receptor which revealed different trajectories passing through the gap between TM helices IV and V for both receptors The side-chain flexibility of Tyr5.38 was significantly different in the two receptor subtypes, as assessed is a way of connecting the orthosteric binding site and the membrane core for lipophilic melatonin receptor

sympatholytic treatments (such as β-blockers) and renin-angiotensin system inhibitors or mineralocorticoid receptor Synthesis and release of these hormones in the adrenals is tightly regulated by adrenal G protein-coupled receptors (GPCRs), such as adrenergic receptors and AngII receptors. context of chronic HF, by focusing on the 2 best studied adrenal GPCR types in that context, adrenergic receptors and AngII receptors (AT 1 Rs).

Self-docking and cross-docking simulations of G protein-coupled receptor-ligand complexes: Impact of ligand type and receptor activation state G protein-coupled receptors (GPCR) are the largest family of cell surface receptors in vertebrates. Likewise, the relative importance of receptor activation state and ligand function differences have also Receptor conformational sampling in advance of docking or receptor conformational adjustment after docking

neurotrophic factor-α1 (NF-α1/carboxypeptidase E, CPE) and human 5-HTR1E, a G protein-coupled serotonin receptor Thus, NF-α1/CPE uniquely interacts with serotonin receptor 5-HTR1E to activate the β-arrestin/ERK/CREB

August 2022 "Opioid receptors (ORs) represent one of the most significant groups of G-protein coupled receptor (GPCR) drug targets and also act as prototypical models for GPCR function.

September 2022 Cell-Type-Specific Effects of the Ovarian Cancer G-Protein Coupled Receptor (OGR1) on Proton-sensing G-protein coupled receptors are activated by acidic environments, but their role in fibrosis Here, we report that the Ovarian Cancer G-Protein Coupled Receptor1 (OGR1 or GPR68) has dual roles in

Mitogen-Activated Protein Kinase and Nuclear Factor- κ B "Emerging evidence implicates the G-protein coupled receptor

August 2022 "The atypical chemokine receptor 1 (ACKR1) was discovered on erythrocytes as the Duffy blood group antigen ( Cutbush et al., 1950 ), also called Duffy-antigen/receptor for chemokines, or DARC (

The company has long-standing expertise in G protein–coupled receptor (GPCR) biology—one of the most capabilities span the full spectrum of GPCR families, including aminergic, peptide, lipid, and chemosensory receptors (such as bitter and metabolic receptors).

by sea bass gonadotropin-inhibitory hormone peptides in COS-7 cells transfected with their cognate receptor significantly decreased forskolin-elicited CRE-luc activity in COS-7 cells transfected with their cognate receptor Notably, GnIH2 antagonized Kiss2-evoked CRE-luc activity in COS-7 cells expressing GnIHR and Kiss2 receptor

Questions about how opioids impair breathing, why xylazine complicates interventions, and how receptor-level This approach makes her models not just rigorous, but translational—bridging the gap between receptor She is especially interested in mu-opioid receptor signaling  and how xylazine, as an alpha-2 adrenergic That personal loss transforms complex receptor pharmacology into something immediate and human.

Bigger Picture: GPCR Science Meets Public Health At its core, Catherine Demery’s research  is about receptors and signaling pathways—how mu-opioid  and alpha-2 adrenergic receptors  interact to disrupt breathing Fentanyl, through the mu-opioid receptor, blunts the brainstem’s inspiratory drive so that each breath By displacing opioids from the mu-opioid receptor, it restores breathing within minutes. But that mechanism has no impact on xylazine, which works through alpha-2 adrenergic receptors.

conditions, what appears to be a second high-affinity site may simply reflect kinetic factors—such as ligand-receptor-G

GABAB receptors inhibit Ca2+ entry, whereas 5-HT1B receptors target SNARE complexes. We demonstrate in male and female rats that GABAB receptors receptors alter Pr, whereas 5-HT1B receptors GABAB receptors alter Pr leaving synaptic properties unchanged, while 5-HT1B receptors fundamentally change properties of synaptic transmission, modifying AMPA receptor but sparing NMDA receptor responses Co-activation of these receptors allows synaptic integration because of convergence of GABAB receptor

The sixth transmembrane region of a pheromone G-protein coupled receptor, Map3, is implicated in discrimination the molecular recognition of two peptidyl mating pheromones by their corresponding G-protein coupled receptors Although such pheromone/receptor systems are likely to function in both mate choice and prezygotic isolation , very few studies have focused on the stringency of pheromone receptors. GPCRs might reflect the significantly distinct stringency/flexibility of their respective pheromone/receptor

Watch Episode 172 What happens when the career you planned no longer feels right? For Catherine Demery, it meant rewriting everything on her own terms. She entered undergrad set on becoming a pharmacist. After excelling in the PCAT and gaining admission to pharmacy school at the University of Michigan, it seemed like her path was locked in. But something shifted. “I kind of had an identity crisis because I think I realized in that moment that I didn't want to be a pharmacist but I had tailored four years of my life to doing so." Two weeks before orientation, Catherine deferred her acceptance. It was a bold, uncertain move—but one that became the catalyst for a new trajectory. She found herself drawn toward the science behind the drugs, rather than their clinical application. That insight eventually led her into industry. Learning the Lab, Learning Herself During her time at the contract research organization (CRO) in Ann Arbor, Catherine was immersed in analytical work under stringent GLP/GMP standards. It was here that the disciplined structure of industry science helped her re-find purpose and build confidence for what came next. “This wasn’t with much foresight for a couple years down the road. It was mostly just because, I need to be back in the lab.” In that environment, every project brought new challenges—deadlines, documentation, and deliverables for paying clients. Catherine’s methodical retention of those skills later gave her a solid foundation in her academic work, even when expectations were looser in academia. The Spark of Addiction Science After two years in industry, Catherine enrolled in a master’s program in pharmacogenomics at Manchester University. There, she chose to write a review on genetic variation in susceptibility to alcoholism and opioid addiction—a decision that would reshape her academic ambitions. “...I had a light bulb moment where I felt for the first time in my life, I understood why people pursued a PhD. I was staying up super late. I was excited to work on this, till 2 or 3 a.m.” That project was her lightbulb moment. She finally understood what it meant to be driven by a research question, not just assigned to one. For the first time, she saw herself as a future researcher, not just a technician or a student. A Detour Through Immunology Her growing interest in addiction led her to the NIH’s Perinatology Research Branch in Detroit. While her work there focused on immunological changes in pregnancy—not addiction—it was a valuable chapter. She gained exposure to in vivo models, immunology, and complex study design, while also getting closer to patient-centered research. “It really forced me to kind of patch up all my immunology holes and then apply them. I came away from that job with just a whole new appreciation for immunology and for pregnancy. It was really, really fascinating… and just eye opening to a part of the world that I don’t think I would have put that much thought into ever again.” This experience sharpened her conceptual range and prepared her for the next step. Returning to the Opioid Questions That Mattered Now, as a PhD candidate in the Traynor and Anand labs at the University of Michigan, Catherine is focused on the mechanisms of opioid-induced respiratory depression, particularly involving fentanyl and xylazine. Her current work examines how these substances, when used alone or together, impair breathing in mice. She uses whole-body plethysmography and pulse oximetry to dissect the specific ways these drugs impact the respiratory cycle. It’s rigorous pharmacology, but deeply tied to urgent public health needs. And it’s also deeply personal. "I've always been really passionate and somewhat sensitive to people who struggle with opioid abuse. I had a few friends who became addicted and, really sadly, many of whom actually passed away as a result of an overdose. And so, that certainly shaped my interests and passions as a scientist." What Can You Learn from Catherine’s Story? A career pivot is not a failure—it’s a refined strategy. Industry can build skills that academia often overlooks. Your passion might not come first—it might come from doing the work. The most impactful science is often personal. Technical discipline is transferable—even across research cultures. The Importance of Passion in Research Catherine's journey highlights the importance of passion in research. It is not just about following a predetermined path; it is about discovering what truly drives you. Passion can lead to groundbreaking discoveries and a fulfilling career. When you find something that excites you, it can transform your work into a source of joy and motivation. Catherine's experience serves as a reminder that it is never too late to change direction and pursue what you love. Embracing Change and Uncertainty Change can be daunting, especially when it involves stepping away from a well-defined career path. However, embracing uncertainty can lead to unexpected opportunities. Catherine's decision to defer pharmacy school was a leap of faith that opened new doors. In life and career, taking risks can lead to personal and professional growth. It is essential to remain open to new experiences and to trust your instincts. This mindset can lead to a more fulfilling and successful career. Conclusion: A Journey of Self-Discovery Catherine Demery's story is one of self-discovery and resilience. It shows that career paths can evolve, and that it is possible to find fulfillment in unexpected places. Her journey illustrates the power of following one's passion and the importance of being adaptable in the face of change. In the end, it is about finding what resonates with you and pursuing it wholeheartedly. Catherine's experience serves as an inspiration for anyone considering a career change or seeking to align their work with their passions. _______ Keyword Cloud : #XylazineResearch #OpioidPharmacology #muOpioidReceptor #RespiratoryDepression #AddictionScience #DrGPCRecosystem #FentanylOverdose

When pharmacologists misinterpret how an antagonist interacts with its receptor, the consequences ripple But if the antagonist binds tightly and dissociates slowly, the receptor remains blocked, even at high Antagonist “hogs” the receptor, depressing the response, even if more agonist is added. Common misconceptions  arise when irreversible binding, receptor reserve, or allosteric effects mimic He challenges the idea that curve shape alone is diagnostic, pointing out how features like receptor