Richard Neubig, MD PhD

he/his/him
Professor Emeritus and Director, Drug Discovery Program
Pharmacology & Toxicology

Bio

Dr. Neubig received his B.S. in chemistry from the University of Michigan, M.D. from Harvard Medical School in the Harvard-MIT Program in Health Sciences and Technology, and Ph.D. in pharmacology from Harvard University. He trained in internal medicine at University of Michigan Hospitals then joined the faculty in the departments of Pharmacology and Internal Medicine (Hypertension Division) from 1984-2013. He was Chair of Pharmacology & Toxicology at Michigan State University from 2013-2021 and is now Professor of Pharmacology & Toxicology and Director of MSU Drug Discovery. He has studied GPCR signaling for most of his career and is currently testing gene therapies for G protein disorders that result in movement disorders and epilepsy. Since 2000, he has had a major focus on academic drug discovery. He founded the Center for Chemical Genomics at the University of Michigan and MSU Drug Discovery at Michigan State University. His own efforts in drug discovery have focused on cancer, scleroderma, and other fibrotic diseases. He was the co-founder of a start-up company FibrosIX Inc. He was the founding chair of the ASPET Division of Molecular Pharmacology, President of ASPET in 2013-2014 and is a Fellow of ASPET (FASPET). He received both the Astellas and ASPET-Pharmacia awards for translational pharmacology. He has been active in international pharmacology having served on the IUPHAR Receptor Nomenclature Committee from 2000-2015 for which he was GPCR co-chair. He is a Fellow of the American Association for the Advancement of Science (AAAS) and is past chair of Section S, Pharmaceutical Sciences of AAAS. He is an active birder and loves being out in nature and is always thrilled to be with his grandchildren (ages 0, 2 and 6).

Colleges

• College of Human Medicine
• College of Veterinary Medicine
• College of Osteopathic Medicine

Associations

• Interim Chief, Nicholas V. Perricone, MD Division of Dermatology

Programs

• Neuroscience Program
• Integrated Pharmacological Sciences Training Program Co-Director

Facilities

• Assay Development and Drug Repurposing Core (Director)

Education

• MD, Medicine, Harvard Medical School (1975—1981)
• PhD, Pharmacology, Harvard University (1977—1980)
• BS Chem, Chemistry, University of Michigan (1971—1975)

Works

• Pirin does not bind to p65 or regulate NFκB-dependent gene expression but does modulate cellular quercetin levels. (2024-12-04)
• Inhibition of the Rho/MRTF pathway improves the response of BRAF‐resistant melanoma to PD1/PDL1 blockade. International Journal of Cancer (2024)
• Mechanistic insights into Rho/MRTF inhibition-induced apoptotic events and prevention of drug resistance in melanoma: Implications for the involvement of pirin. (2024-09-24)
• Inhibition of the Rho/MRTF pathway improves the response of BRAF-resistant melanoma to PD1/PDL1 blockade. (2023-12-21)
• Role of Rho/MRTF in Aggressive Vemurafenib-Resistant Murine Melanomas and Immune Checkpoint Upregulation. International Journal of Molecular Sciences (2023-09-07)
• Targeting ATP12A, a Nongastric Proton Pump α Subunit, for Idiopathic Pulmonary Fibrosis Treatment. American journal of respiratory cell and molecular biology (2023-06-01)
• Development of a Cell-Based AlphaLISA Assay for High-Throughput Screening for Small Molecule Proteasome Modulators. ACS Omega (2023-05-02)
• Mice with monoallelic GNAO1 loss exhibit reduced inhibitory synaptic input to cerebellar Purkinje cells. Journal of Neurophysiology (2022-03-01)
• Prevention of Drug-Induced Lung Fibrosis via Inhibition of the MRTF/SRF Transcription Pathway. (2021-09-10)
• G protein-coupled estrogen receptor in GtoPdb v.2021.3. IUPHAR/BPS Guide to Pharmacology CITE (2021-09-02)
• Inhibition of the Myocardin-Related Transcription Factor Pathway Increases Efficacy of Trametinib in NRAS-Mutant Melanoma Cell Lines. Cancers (2021-04-22)
• Inhibition of the Myocardin-Related Transcription Factor Pathway Increases Efficacy of Trametinib in NRAS-Mutant Melanoma Cell Lines. Cancers (2021)
• BRAF inhibitor resistance confers increased sensitivity to mitotic inhibitors. (2021-04-15)
• Ibrutinib blocks YAP1 activation and reverses BRAFi resistance in melanoma cells. (2020-03-26)
• Rho-mediated signaling promotes BRAF inhibitor resistance in de-differentiated melanoma cells. Oncogene (2020-02-13)
• An Interhelical Salt Bridge Controls Flexibility and Inhibitor Potency for Regulators of G-protein Signaling Proteins 4, 8, and 19. Molecular Pharmacology (2019-12-22)
• Loss-of-Function Mutations in Human Regulator of G Protein Signaling RGS2 Differentially Regulate Pharmacological Reactivity of Resistance Vasculature. Molecular pharmacology (2019-10-23)
• Inhibition of the Myocardin-Related Transcription Factor pathway increases efficacy of Trametinib in NRAS-mutant melanoma cell lines. (2019-09-19)
• G protein-coupled estrogen receptor (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database. IUPHAR/BPS Guide to Pharmacology CITE (2019-09-16)
• Identifying chemopreventive agents for obesity-associated cancers using an efficient, 3D high-throughput transformation assay. Scientific Reports (2019-07-16)
• Spermine in semen of male sea lamprey acts as a sex pheromone. PLoS biology (2019)
• Mice with GNAO1 R209H Movement Disorder Variant Display Hyperlocomotion Alleviated by Risperidone. BioRxiv (2019-06-06)
• RAC1P29S Induces a Mesenchymal Phenotypic Switch via Serum Response Factor to Promote Melanoma Development and Therapy Resistance. Cancer cell (2019)
• The Rho/MRTF pathway inhibitor CCG-222740 reduces stellate cell activation and modulates immune cell populations in KrasG12D; Pdx1-Cre (KC) mice. Scientific Reports (2019-05-08)
• 5-Aryl-1,3,4-oxadiazol-2-ylthioalkanoic Acids: A Highly Potent New Class of Inhibitors of Rho/Myocardin-Related Transcription Factor (MRTF)/Serum Response Factor (SRF)-Mediated Gene Transcription as Potential Antifibrotic Agents for Scleroderma. Journal of medicinal chemistry (2019)
• Mouse models of GNAO1-associated movement disorder: Allele- and sex-specific differences in phenotypes. PLOS ONE (2019-01-25)
• A Two-Pulse Cellular Stimulation Test Elucidates Variability and Mechanisms in Signaling Pathways. Biophysical journal (2019)
• Interplay of cysteine exposure and global protein dynamics in small-molecule recognition by a regulator of G-protein signaling protein. Proteins (2018)
• In vitro and in vivo delivery of a sustained release nanocarrier-based formulation of an MRTF/SRF inhibitor in conjunctival fibrosis. Journal of nanobiotechnology (2018)
• Interpreting Hydrogen–Deuterium Exchange Events in Proteins Using Atomistic Simulations: Case Studies on Regulators of G-Protein Signaling Proteins. The Journal of Physical Chemistry B (2018-10-11)
• Identification of Pirin as a Molecular Target of the CCG-1423/CCG- 203971 Series of Anti-Fibrotic and Anti-Metastatic Compounds. (2018)
• Role of hippocampal 5-HT1A receptors in the antidepressant-like phenotype of mice expressing RGS-insensitive Gαi2 protein. Neuropharmacology (2018)
• Rho-mediated gene transcription promotes BRAF inhibitor resistance in de-differentiated melanoma cells. BirRxiv (2018-08-01)
• A mechanistic review on GNAO1-associated movement disorder. Neurobiology of Disease (2018)
• Mouse Models of GNAO1-Associated Movement Disorder: Allele- and sex-specific differences in phenotypes. (2018-06-29)
• Differential Protein Dynamics of Regulators of G-Protein Signaling: Role in Specificity of Small-Molecule Inhibitors. Journal of the American Chemical Society (2018-03-07)
• Role of signalling molecules in behaviours mediated by the δ opioid receptor agonist SNC80. British journal of pharmacology (2018)
• Human Missense Mutations in Regulator of G Protein Signaling 2 Affect the Protein Function Through Multiple Mechanisms. Molecular pharmacology (2017)
• Movement disorder in GNAO1 encephalopathy associated with gain-of-function mutations. Neurology (2017)
• Optimisation of Intestinal Fibrosis and Survival in the Mouse S. Typhimurium Model for Anti-fibrotic Drug Discovery and Preclinical Applications. Journal of Crohn's & colitis (2017)
• A central role for R7bp in the regulation of itch sensation. Pain (2017)
• Local delivery of novel MRTF/SRF inhibitors prevents scar tissue formation in a preclinical model of fibrosis. Scientific reports (2017)
• Pharmacokinetic optimitzation of CCG-203971: Novel inhibitors of the Rho/MRTF/SRF transcriptional pathway as potential antifibrotic therapeutics for systemic scleroderma. Bioorganic & medicinal chemistry letters (2017)
• The DRY motif and the four corners of the cubic ternary complex model. Cellular signalling (2017)
• Regulator of G Protein Signaling 6 Protects the Heart from Ischemic Injury. The Journal of pharmacology and experimental therapeutics (2016)
• Chemerin-induced arterial contraction is Gi- and calcium-dependent. Vascular pharmacology (2016)
• Pharmacological Inhibition of Myocardin-related Transcription Factor Pathway Blocks Lung Metastases of RhoC-Overexpressing Melanoma. Molecular cancer therapeutics (2016)
• The role of regulator of G protein signaling 4 in delta-opioid receptor-mediated behaviors. Psychopharmacology (2016)
• M4 Muscarinic Receptor Signaling Ameliorates Striatal Plasticity Deficits in Models of L-DOPA-Induced Dyskinesia. Neuron (2016)
• Small-Molecule Inhibition of Rho/MKL/SRF Transcription in Prostate Cancer Cells: Modulation of Cell Cycle, ER Stress, and Metastasis Gene Networks. Microarrays (Basel, Switzerland) (2016)
• Digoxin-Mediated Upregulation of RGS2 Protein Protects against Cardiac Injury. The Journal of pharmacology and experimental therapeutics (2016)
• RGS Proteins and Gαi2 Modulate Sleep, Wakefulness, and Disruption of Sleep/ Wake States after Isoflurane and Sevoflurane Anesthesia. Sleep (2016)
• Band-pass processing in a GPCR signaling pathway selects for NFAT transcription factor activation. Integrative biology : quantitative biosciences from nano to macro (2015)
• RGS-Insensitive G Proteins as In Vivo Probes of RGS Function. Progress in molecular biology and translational science (2015)
• FBXO44-Mediated Degradation of RGS2 Protein Uniquely Depends on a Cullin 4B/DDB1 Complex. PloS one (2015)
• Selectivity and anti-Parkinson's potential of thiadiazolidinone RGS4 inhibitors. ACS chemical neuroscience (2015)
• Inhibition of myocardin-related transcription factor/serum response factor signaling decreases lung fibrosis and promotes mesenchymal cell apoptosis. The American journal of pathology (2015)
• International Union of Basic and Clinical Pharmacology. XC. multisite pharmacology: recommendations for the nomenclature of receptor allosterism and allosteric ligands. Pharmacological reviews (2014)
• Identification of protein kinase C activation as a novel mechanism for RGS2 protein upregulation through phenotypic screening of natural product extracts. Molecular pharmacology (2014)
• Induction of the matricellular protein CCN1 through RhoA and MRTF-A contributes to ischemic cardioprotection. Journal of molecular and cellular cardiology (2014)
• Conditional disruption of interactions between Gαi2 and regulator of G protein signaling (RGS) proteins protects the heart from ischemic injury. BMC pharmacology & toxicology (2014)
• Cellular mechanisms of tissue fibrosis. 8. Current and future drug targets in fibrosis: focus on Rho GTPase-regulated gene transcription. American journal of physiology. Cell physiology (2014)
• Gain-of-function mutation in Gnao1: a murine model of epileptiform encephalopathy (EIEE17)?. Mammalian genome : official journal of the International Mammalian Genome Society (2014)
• Targeting the myofibroblast genetic switch: inhibitors of myocardin-related transcription factor/serum response factor-regulated gene transcription prevent fibrosis in a murine model of skin injury. The Journal of pharmacology and experimental therapeutics (2014)
• Novel Rho/MRTF/SRF inhibitors block matrix-stiffness and TGF-β-induced fibrogenesis in human colonic myofibroblasts. Inflammatory bowel diseases (2014)
• Redox modification of nuclear actin by MICAL-2 regulates SRF signaling. Cell (2014)
• Regulation of protease-activated receptor 1 signaling by the adaptor protein complex 2 and R4 subfamily of regulator of G protein signaling proteins. The Journal of biological chemistry (2013)
• The Concise Guide to PHARMACOLOGY 2013/14: overview. British journal of pharmacology (2013)
• Conformational dynamics of a regulator of G-protein signaling protein reveals a mechanism of allosteric inhibition by a small molecule. ACS chemical biology (2013)
• Reversible inhibitors of regulators of G-protein signaling identified in a high-throughput cell-based calcium signaling assay. Cellular signalling (2013)
• Microfluidic interrogation and mathematical modeling of multi-regime calcium signaling dynamics. Integrative biology : quantitative biosciences from nano to macro (2013)
• Design and synthesis of tag-free photoprobes for the identification of the molecular target for CCG-1423, a novel inhibitor of the Rho/MKL1/SRF signaling pathway. Beilstein journal of organic chemistry (2013)
• International Union of Basic and Clinical Pharmacology. LXXXVIII. G protein-coupled receptor list: recommendations for new pairings with cognate ligands. Pharmacological reviews (2013)
• Optimization of novel nipecotic bis(amide) inhibitors of the Rho/MKL1/SRF transcriptional pathway as potential anti-metastasis agents. Bioorganic & medicinal chemistry letters (2013)
• Detection of G protein-selective G protein-coupled receptor (GPCR) conformations in live cells. The Journal of biological chemistry (2013)
• Differential control of opioid antinociception to thermal stimuli in a knock-in mouse expressing regulator of G-protein signaling-insensitive Gαo protein. The Journal of Neuroscience (2013)
• NMR methods for detection of small molecule binding to RGS4. Methods in enzymology (2013)
• Regulation of G protein signaling by the 70kDa heat shock protein. Cellular signalling (2012)
• IUPHAR-DB: updated database content and new features. Nucleic acids research (2012)
• Toll-like receptor-induced inflammatory cytokines are suppressed by gain of function or overexpression of Gα(i2) protein. Inflammation (2012)
• The loss of RGS protein-Gα(i2) interactions results in markedly impaired mouse neutrophil trafficking to inflammatory sites. Molecular and cellular biology (2012)
• Increased CD39 nucleotidase activity on microparticles from patients with idiopathic pulmonary arterial hypertension. PloS one (2012)
• Cardiotonic steroids stabilize regulator of G protein signaling 2 protein levels. Molecular pharmacology (2012)
• MScreen: an integrated compound management and high-throughput screening data storage and analysis system. Journal of biomolecular screening (2012)
• Gαi2 signaling: friend or foe in cardiac injury and heart failure?. Naunyn-Schmiedeberg's archives of pharmacology (2012)
• Small Molecule Inhibitors of Regulator of G Protein Signalling (RGS) Proteins. ACS medicinal chemistry letters (2012)
• How to use the IUPHAR receptor database to navigate pharmacological data. Methods in molecular biology (Clifton, N.J.) (2012)
• A newly identified complex of spinophilin and the tyrosine phosphatase, SHP-1, modulates platelet activation by regulating G protein-dependent signaling. Blood (2011)
• Complementary cell-based high-throughput screens identify novel modulators of the unfolded protein response. Journal of biomolecular screening (2011)
• Hi-Fi transmission of periodic signals amid cell-to-cell variability. Molecular bioSystems (2011)
• A nanomolar-potency small molecule inhibitor of regulator of G-protein signaling proteins. Biochemistry (2011)
• Gα(i2)-mediated protection from ischaemic injury is modulated by endogenous RGS proteins in the mouse heart. Cardiovascular research (2011)
• Major developments in our understanding of G protein-coupled receptors. Advances in pharmacology (San Diego, Calif.) (2011)
• RGS-insensitive Gα subunits: probes of Gα subtype-selective signaling and physiological functions of RGS proteins. Methods in molecular biology (Clifton, N.J.) (2011)
• Phase-locked signals elucidate circuit architecture of an oscillatory pathway. PLoS computational biology (2010)
• Gα subunit coordinates with ephrin-B to balance self-renewal and differentiation in neural progenitor cells. Stem cells (Dayton, Ohio) (2010)
• RGS/Gi2alpha interactions modulate platelet accumulation and thrombus formation at sites of vascular injury. Blood (2010)
• Analyzing binding data. Current protocols in neuroscience (2010)
• Mind your salts: when the inactive constituent isn't. Molecular pharmacology (2010)
• Thinking outside of the "RGS box": new approaches to therapeutic targeting of regulators of G protein signaling. Molecular pharmacology (2010)
• Allosteric inhibition of the regulator of G protein signaling-Galpha protein-protein interaction by CCG-4986. Molecular pharmacology (2010)
• RGS inhibition at G(alpha)i2 selectively potentiates 5-HT1A-mediated antidepressant effects. Proceedings of the National Academy of Sciences of the United States of America (2010)
• Reversible, allosteric small-molecule inhibitors of regulator of G protein signaling proteins. Molecular pharmacology (2010)
• GPCR-OKB: the G Protein Coupled Receptor Oligomer Knowledge Base. Bioinformatics (Oxford, England) (2010)
• Regulators of G protein signaling proteins as targets for drug discovery. Progress in molecular biology and translational science (2010)
• Use of flow cytometric methods to quantify protein-protein interactions. Current protocols in cytometry (2010)
• Design, synthesis and prostate cancer cell-based studies of analogs of the Rho/MKL1 transcriptional pathway inhibitor, CCG-1423. Bioorganic & medicinal chemistry letters (2009)
• Differential modulation of mu-opioid receptor signaling to adenylyl cyclase by regulators of G protein signaling proteins 4 or 8 and 7 in permeabilised C6 cells is Galpha subtype dependent. Journal of neurochemistry (2009)
• Isoflurane-induced changes in righting response and breathing are modulated by RGS proteins. Anesthesia and analgesia (2009)
• A conserved hydrophobic surface of the LARG pleckstrin homology domain is critical for RhoA activation in cells. Cellular signalling (2009)
• Polyplexed flow cytometry protein interaction assay: a novel high-throughput screening paradigm for RGS protein inhibitors. Journal of biomolecular screening (2009)
• A covalent peptide inhibitor of RGS4 identified in a focused one-bead, one compound library screen. BMC pharmacology (2009)
• Identification of thieno[3,2-b]pyrrole derivatives as novel small molecule inhibitors of neurotropic alphaviruses. The Journal of infectious diseases (2009)
• GNAI2 and regulators of G protein signaling as a potential Noonan syndrome mechanism. Medical hypotheses (2009)
• International Union of Pharmacology. LXXII. Recommendations for trace amine receptor nomenclature. Pharmacological reviews (2009)
• High-throughput screening for small-molecule inhibitors of LARG-stimulated RhoA nucleotide binding via a novel fluorescence polarization assay. Journal of biomolecular screening (2009)
• Regulator of G protein signaling protein suppression of Galphao protein-mediated alpha2A adrenergic receptor inhibition of mouse hippocampal CA3 epileptiform activity. Molecular pharmacology (2009)
• A juxtamembrane mutation in the N terminus of the dopamine transporter induces preference for an inward-facing conformation. Molecular pharmacology (2008)
• Assembly of high order G alpha q-effector complexes with RGS proteins. The Journal of biological chemistry (2008)
• IUPHAR-DB: the IUPHAR database of G protein-coupled receptors and ion channels. Nucleic acids research (2008)
• In vitro protein kinase activity measurement by flow cytometry. Analytical biochemistry (2008)
• Small molecule protein-protein interaction inhibitors as CNS therapeutic agents: current progress and future hurdles. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology (2008)
• And the winner is ... RGS4!. Circulation research (2008)
• Novel peptide ligands of RGS4 from a focused one-bead, one-compound library. Chemical biology & drug design (2008)
• Microfabricated channel array electrophoresis for characterization and screening of enzymes using RGS-G protein interactions as a model system. Analytical chemistry (2008)
• Structure of Galphaq-p63RhoGEF-RhoA complex reveals a pathway for the activation of RhoA by GPCRs. Science (New York, N.Y.) (2007)
• Resistance to diet-induced obesity and improved insulin sensitivity in mice with a regulator of G protein signaling-insensitive G184S Gnai2 allele. Diabetes (2007)
• Phagocyte-derived catecholamines enhance acute inflammatory injury. Nature (2007)
• CCG-1423: a small-molecule inhibitor of RhoA transcriptional signaling. Molecular cancer therapeutics (2007)
• Fluorescence-based adenylyl cyclase assay adaptable to high throughput screening. Combinatorial chemistry & high throughput screening (2007)
• Requirements and ontology for a G protein-coupled receptor oligomerization knowledge base. BMC bioinformatics (2007)
• International Union of Basic and Clinical Pharmacology. LXVII. Recommendations for the recognition and nomenclature of G protein-coupled receptor heteromultimers. Pharmacological reviews (2007)
• Capillary electrophoresis assay for G protein-coupled receptor-mediated GTPase activity. Analytical chemistry (2007)
• Endogenous RGS proteins modulate SA and AV nodal functions in isolated heart: implications for sick sinus syndrome and AV block. American journal of physiology. Heart and circulatory physiology (2007)
• Missing links: mechanisms of protean agonism. Molecular pharmacology (2007)
• Under the microscope: single molecule symposium at the University of Michigan, 2006. Biopolymers (2007)
• N-terminal residues control proteasomal degradation of RGS2, RGS4, and RGS5 in human embryonic kidney 293 cells. Molecular pharmacology (2007)
• The highly conserved DRY motif of class A G protein-coupled receptors: beyond the ground state. Molecular pharmacology (2006)
• Identification of small-molecule inhibitors of RGS4 using a high-throughput flow cytometry protein interaction assay. Molecular pharmacology (2006)
• Pleiotropic phenotype of a genomic knock-in of an RGS-insensitive G184S Gnai2 allele. Molecular and cellular biology (2006)
• Mechanism of action and structural requirements of constrained peptide inhibitors of RGS proteins. Chemical biology & drug design (2006)
• Endogenous RGS proteins and Galpha subtypes differentially control muscarinic and adenosine-mediated chronotropic effects. Circulation research (2006)
• International Union of Pharmacology. LVI. Ghrelin receptor nomenclature, distribution, and function. Pharmacological reviews (2005)
• Regions in the G protein gamma subunit important for interaction with receptors and effectors. Molecular pharmacology (2005)
• International Union of Pharmacology. XLVI. G protein-coupled receptor list. Pharmacological reviews (2005)
• Galanin receptor 1 has anti-proliferative effects in oral squamous cell carcinoma. The Journal of biological chemistry (2005)
• Receptor-antagonist interactions in the complexes of agouti and agouti-related protein with human melanocortin 1 and 4 receptors. Biochemistry (2005)
• Regulators of G protein signaling & drugs of abuse. Molecular interventions (2005)
• Affinity assays using fluorescence anisotropy with capillary electrophoresis separation. Analytical chemistry (2004)
• Real-time detection of basal and stimulated G protein GTPase activity using fluorescent GTP analogues. The Journal of biological chemistry (2004)
• Thrombin and lysophosphatidic acid receptors utilize distinct rhoGEFs in prostate cancer cells. The Journal of biological chemistry (2004)
• Endogenous regulator of G protein signaling proteins suppress Galphao-dependent, mu-opioid agonist-mediated adenylyl cyclase supersensitization. The Journal of pharmacology and experimental therapeutics (2004)
• Structure-based design, synthesis, and pharmacologic evaluation of peptide RGS4 inhibitors. The journal of peptide research : official journal of the American Peptide Society (2004)
• RGS-insensitive G-protein mutations to study the role of endogenous RGS proteins. Methods in enzymology (2004)
• Real-time analysis of ternary complex on particles: direct evidence for partial agonism at the agonist-receptor-G protein complex assembly step of signal transduction. The Journal of biological chemistry (2004)
• Ribozyme- and siRNA-mediated suppression of RGS-containing RhoGEF proteins. Methods in enzymology (2004)
• Structure-based design, synthesis, and activity of peptide inhibitors of RGS4 GAP activity. Methods in enzymology (2004)
• Dimerization in aminergic G-protein-coupled receptors: application of a hidden-site class model of evolution. Biochemistry (2003)
• International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification. XXXVIII. Update on terms and symbols in quantitative pharmacology. Pharmacological reviews (2003)
• Depicting a protein's two faces: GPCR classification by phylogenetic tree-based HMMs. FEBS letters (2003)
• Ligand-receptor-G-protein molecular assemblies on beads for mechanistic studies and screening by flow cytometry. Molecular pharmacology (2003)
• Detection of G proteins by affinity probe capillary electrophoresis using a fluorescently labeled GTP analogue. Analytical chemistry (2003)
• Diabetic neuropathy: inhibitory G protein dysfunction involves PKC-dependent phosphorylation of Goalpha. Journal of neurochemistry (2003)
• Inverse agonist activity of agouti and agouti-related protein. Peptides (2003)
• Stimulation of cellular signaling and G protein subunit dissociation by G protein betagamma subunit-binding peptides. The Journal of biological chemistry (2003)
• Endogenous RGS protein action modulates mu-opioid signaling through Galphao. Effects on adenylyl cyclase, extracellular signal-regulated kinases, and intracellular calcium pathways. The Journal of biological chemistry (2003)
• Regulators of G protein signaling (RGS proteins): novel central nervous system drug targets. The journal of peptide research : official journal of the American Peptide Society (2002)
• A spatial focusing model for G protein signals. Regulator of G protein signaling (RGS) protien-mediated kinetic scaffolding. The Journal of biological chemistry (2002)
• Fluorescence analysis of receptor-G protein interactions in cell membranes. Biochemistry (2002)
• Analyzing radioligand binding data. Current protocols in neuroscience (2002)
• Expression of novel splice variants of the G protein subunit, Go alpha, is tissue-specific and age-dependent in the rat. Gene (2002)
• Mutagenesis and peptide analysis of the DRY motif in the alpha2A adrenergic receptor: evidence for alternate mechanisms in G protein-coupled receptors. Biochemical and biophysical research communications (2002)
• Receptor-selective effects of endogenous RGS3 and RGS5 to regulate mitogen-activated protein kinase activation in rat vascular smooth muscle cells. The Journal of biological chemistry (2002)
• NMR structure of the second intracellular loop of the alpha 2A adrenergic receptor: evidence for a novel cytoplasmic helix. Biochemistry (2002)
• Regulators of G-protein signalling as new central nervous system drug targets. Nature reviews. Drug discovery (2002)
• AT1 receptor mutant lacking heterotrimeric G protein coupling activates the Src-Ras-ERK pathway without nuclear translocation of ERKs. The Journal of biological chemistry (2002)
• Fluorescence approaches to study G protein mechanisms. Methods in enzymology (2002)
• Using evolutionary methods to study G-protein coupled receptors. Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing (2002)
• ANG II type 1 receptor downregulation does not require receptor endocytosis or G protein coupling. American journal of physiology. Cell physiology (2001)
• Receptor-G protein gamma specificity: gamma11 shows unique potency for A(1) adenosine and 5-HT(1A) receptors. Biochemistry (2001)
• Regulator of G protein signaling proteins: novel multifunctional drug targets. The Journal of pharmacology and experimental therapeutics (2001)
• Fluorescent BODIPY-GTP analogs: real-time measurement of nucleotide binding to G proteins. Analytical biochemistry (2001)
• Real-time analysis of G protein-coupled receptor reconstitution in a solubilized system. The Journal of biological chemistry (2001)
• Inverse agonist activity at the alpha(2A)-adrenergic receptor. Molecular pharmacology (2001)
• Selective inactivation of guanine-nucleotide-binding regulatory protein (G-protein) alpha and betagamma subunits by urea. The Biochemical journal (2001)
• Molecular cloning and characterization of a novel regulator of G-protein signaling from mouse hematopoietic stem cells. The Journal of biological chemistry (2001)
• Timing is everything the role of kinetics in G protein activation. Life sciences (2000)
• Walker A lysine mutations of TAP1 and TAP2 interfere with peptide translocation but not peptide binding. The Journal of biological chemistry (2000)
• Rapid kinetics of regulator of G-protein signaling (RGS)-mediated Galphai and Galphao deactivation. Galpha specificity of RGS4 AND RGS7. The Journal of biological chemistry (2000)
• Coupling efficacy and selectivity of the human mu-opioid receptor expressed as receptor-Galpha fusion proteins in Escherichia coli. Journal of neurochemistry (2000)
• Agonist-directed trafficking of porcine alpha(2A)-adrenergic receptor signaling in Chinese hamster ovary cells: l-isoproterenol selectively activates G(s). The Journal of pharmacology and experimental therapeutics (2000)
• Analysis of guanine nucleotide binding and exchange kinetics of the Escherichia coli GTPase Era. Journal of bacteriology (2000)
• G(i) activator region of alpha(2A)-adrenergic receptors: distinct basic residues mediate G(i) versus G(s) activation. Molecular pharmacology (1999)
• Interdomain interactions regulate GDP release from heterotrimeric G proteins. Biochemistry (1999)
• A point mutation in Galphao and Galphai1 blocks interaction with regulator of G protein signaling proteins. The Journal of biological chemistry (1998)
• Cotransfection of second and third intracellular loop fragments inhibit angiotensin AT1a receptor activation of phospholipase C in HEK-293 cells. The Journal of pharmacology and experimental therapeutics (1998)
• Determinants of gi1alpha and beta gamma binding. Measuring high affinity interactions in a lipid environment using flow cytometry. The Journal of biological chemistry (1998)
• Roles of G(o)alpha tryptophans in GTP hydrolysis, GDP release, and fluorescence signals. Biochemistry (1998)
• Modulation of K+ and Ca2+ currents in cultured neurons by an angiotensin II type 1a receptor peptide. The American journal of physiology (1997)
• Colloquium on signaling and molecular structure in pharmacology (La Jolla, California, March 11-12, 1997). Molecular pharmacology (1997)
• Novel form of crosstalk between G protein and tyrosine kinase pathways. Proceedings of the National Academy of Sciences of the United States of America (1997)
• Structural requirements for G(o) activation by receptor-derived peptides: activation and modulation domains of the alpha 2-adrenergic receptor i3c region. Molecular pharmacology (1996)
• Partial G protein activation by fluorescent guanine nucleotide analogs. Evidence for a triphosphate-bound but inactive state. The Journal of biological chemistry (1996)
• alpha 2-Adrenoceptors take centre stage at Nashville meeting. Trends in pharmacological sciences (1996)
• Receptor and membrane interaction sites on Gbeta. A receptor-derived peptide binds to the carboxyl terminus. The Journal of biological chemistry (1996)
• Lack of association of G-protein beta 2- and gamma 2-subunit N-terminal fragments provides evidence against the coiled-coil model of subunit-beta gamma assembly. The Biochemical journal (1995)
• Effect of circulating epinephrine on platelet function and hematocrit. Hypertension (Dallas, Tex. : 1979) (1995)
• Rapid kinetics of G protein subunit association: a rate-limiting conformational change?. FEBS letters (1994)
• The novel alpha-2 adrenergic radioligand [3H]-MK912 is alpha-2C selective among human alpha-2A, alpha-2B and alpha-2C adrenoceptors. The Journal of pharmacology and experimental therapeutics (1994)
• Binding of an alpha 2 adrenergic receptor third intracellular loop peptide to G beta and the amino terminus of G alpha. The Journal of biological chemistry (1994)
• Peptides as probes for G protein signal transduction. Cellular signalling (1994)
• Membrane organization in G-protein mechanisms. FASEB journal : official publication of the Federation of American Societies for Experimental Biology (1994)
• Lateral mobility of tetramethylrhodamine (TMR) labelled G protein alpha and beta gamma subunits in NG 108-15 cells. Cellular signalling (1994)
• Multisite interactions of receptors and G proteins: enhanced potency of dimeric receptor peptides in modifying G protein function. Molecular pharmacology (1994)
• Fluorescent guanine nucleotide analogs and G protein activation. The Journal of biological chemistry (1994)
• Coupling an alpha 2-adrenergic receptor peptide to G-protein: a new photolabeling agent. Peptides (1994)
• Subsecond modulation of formyl peptide-linked guanine nucleotide-binding proteins by guanosine 5'-O-(3-thio)triphosphate in permeabilized neutrophils. Molecular pharmacology (1993)
• Compartmentation of receptors and guanine nucleotide-binding proteins in NG108-15 cells: lack of cross-talk in agonist binding among the alpha 2-adrenergic, muscarinic, and opiate receptors. Molecular pharmacology (1993)
• Resonance energy transfer between guanine nucleotide binding protein subunits and membrane lipids. Biochemistry (1993)
• Synthesis and characterization of fluorescently labeled bovine brain G protein subunits. Biochemistry (1993)
• A threshold level of coupled G-proteins is required to transduce neutrophil responses. Journal of immunology (Baltimore, Md. : 1950) (1992)
• Calmodulin binding distinguishes between beta gamma subunits of activated G proteins and transducin. The Biochemical journal (1992)
• Multiple Gi protein subtypes regulate a single effector mechanism. Molecular pharmacology (1991)
• Two peptides from the alpha 2A-adrenergic receptor alter receptor G protein coupling by distinct mechanisms. The Journal of biological chemistry (1991)
• Sensitization of human alpha 1- and alpha 2-adrenergic venous responses by guanadrel sulfate. Clinical pharmacology and therapeutics (1990)
• p-[125I]iodoclonidine is a partial agonist at the alpha 2-adrenergic receptor. Molecular pharmacology (1990)
• Subcellular distribution of alpha 2-adrenergic receptors, pertussis-toxin substrate and adenylate cyclase in human platelets. The Biochemical journal (1990)
• Nonadrenergic [3H]idazoxan binding sites are physically distinct from alpha 2-adrenergic receptors. Molecular pharmacology (1990)
• How does a key fit a flexible lock? Structure and dynamics in receptor function. BioEssays : news and reviews in molecular, cellular and developmental biology (1989)
• The hypertension-coronary heart disease dilemma: the catecholamine-blood platelet connection. Journal of hypertension (1989)
• Rapid kinetics of alpha 2-adrenergic inhibition of adenylate cyclase. Evidence for a distal rate-limiting step. Biochemistry (1989)
• Effects of low-sodium diet on regulation of platelet alpha 2-adrenergic receptors in young and elderly humans. The American journal of physiology (1989)
• Inhibition of adenylate cyclase is mediated by the high affinity conformation of the alpha 2-adrenergic receptor. Molecular pharmacology (1988)
• Temperature effects on alpha 2-adrenergic receptor-Gi interactions. Biochemical pharmacology (1988)
• Mechanism of agonist and antagonist binding to alpha 2 adrenergic receptors: evidence for a precoupled receptor-guanine nucleotide protein complex. Biochemistry (1988)
• Radioiodinated p-iodoclonidine: a high-affinity probe for the alpha 2-adrenergic receptor. Journal of medicinal chemistry (1987)
• Membrane reconstitution of high-affinity alpha 2 adrenergic agonist binding with guanine nucleotide regulatory proteins. Biochemistry (1987)
• Guanine nucleotide effects on catecholamine secretion from digitonin-permeabilized adrenal chromaffin cells. The Journal of biological chemistry (1986)
• Large-scale purification of alpha 2-adrenergic receptor-enriched membranes from human platelets. Persistent association of guanine nucleotides with nonpurified membranes. Biochimica et biophysica acta (1986)
• Agonist and antagonist binding to alpha 2-adrenergic receptors in purified membranes from human platelets. Implications of receptor-inhibitory nucleotide-binding protein stoichiometry. Molecular pharmacology (1985)
• Parallel inactivation of alpha 2-adrenergic agonist binding and Ni by alkaline treatment. FEBS letters (1985)
• Pharmacologic reduction of sympathetic drive increases platelet alpha-2-receptor number. Clinical pharmacology and therapeutics (1985)
• Methods for measuring vascular and nonvascular alpha-receptor sensitivity in humans. Journal of cardiovascular pharmacology (1985)
• Conformations of Torpedo acetylcholine receptor associated with ion transport and desensitization. Biochemistry (1982)
• Immunofluorescence localization at the mammalian neuromuscular junction of the Mr 43,000 protein of Torpedo postsynaptic membranes. Proceedings of the National Academy of Sciences of the United States of America (1981)
• Permeability control by cholinergic receptors in Torpedo postsynaptic membranes: agonist dose-response relations measured at second and millisecond times. Biochemistry (1980)
• Equilibrium binding of [3H]tubocurarine and [3H]acetylcholine by Torpedo postsynaptic membranes: stoichiometry and ligand interactions. Biochemistry (1979)
• Acetylcholine and local anesthetic binding to Torpedo nicotinic postsynaptic membranes after removal of nonreceptor peptides. Proceedings of the National Academy of Sciences of the United States of America (1979)
• Reversal of chronic renal hypertension: role of salt and water excretion. Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.) (1975)

Employment

• Professor, Emeritus, Michigan State University (2024-07-01)
• Professor, Michigan State University (2022-01-01—2024-06-30)
• Professor & Chair, Michigan State University (2013-07-01—2021-12-31)
• Asst/Assoc/Professor, University of Michigan Medical School (1984—2013)
• Intern/Resident, University of Michigan Hospital (1981—1984)