Richard Neubig, M.D., Ph.D.
Pharmacology & Toxicology
B423 Life Sciences
1355 Bogue Street
East Lansing, MI 48823
Fields of Interest: G protein-coupled receptor (GPCR) signaling and intracellular modulators of that signaling. GPCRs are the targets of over 30% of current drugs and we are discovering novel ways to control their function.
- 1975 - B.S. (Chem), University of Michigan with highest honors
- 1981 - M.D., Harvard-MIT Program in Health Sciences and Technology
- 1981 - Harvard Medical School Ph.D., Pharmacology
- 1981 - Resident Internal Medicine, University of Michigan Hospitals
- 1981-1984 - Assistant Professor – Professor, Pharmacology, University of Michigan
- 2004-2013 - Co-director, Center for Chemical Genomics, University of Michigan
- 2013-Current - Professor & Chair, Pharmacology & Toxicology, Michigan State University
Biography & Current Research
The central focus of work in the Neubig lab is on G protein-coupled receptor (GPCR) signaling and intracellular modulators of that signaling. We also undertake academic drug discovery projects in this area. GPCRs are the targets of over 25% of current drugs and we are discovering novel ways to control their function. There are three major programs in the lab:
- Regulator of G protein Signaling (RGS) proteins control the actions of G protein coupled receptors. Blocking their action should enhance signaling while enhancing their action should suppress it. Using high throughput screening, whole genome RNA interference, structure-based drug design, and animal models, we have identified chemical modulators of RGS proteins with potential in neuropsychiatric disorders such as depression, pain, epilepsy, and Parkinson’s disease. We are current examining compound mechanisms and optimizing them for in vivo use.
- Gene transcriptional signaling downstream of the GTPases RhoA/C plays key roles in cancer metastasis and in diseases of fibrosis (scleroderma, pulmonary fibrosis, Crohn’s). We have identified two series of chemical inhibitors of Rho/MRTF/SRF-regulated gene transcription. These compounds show efficacy in models of skin fibrosis and melanoma metastasis.
- Physiological control of G proteins by RGS proteins in brain is explored with mutant mouse models. GNAO1 is mutated in human epilepsy syndromes such as epileptogenic encephalopathy and a mouse model that we have developed shows the same effect of seizures and sudden death. The mechanism of this is being explored relevant to epilepsy and potential therapies. RGS proteins also modulate functions in Fragile X syndrome which may also be a target of RGS therapeutics.
Awards & Achievements
- Phi Beta Kappa, University of Michigan, 1974
- American Institute of Chemists Award, 1975
- Medical Scientist Trainee Program Fellowship, NIH, 1976-1981
- Hartford Foundation Fellowship, 1983-1986
- American Heart Association Established Investigator, 1987-1993
- ASPET-Astellas Award in Translational Pharmacology, 2009
- Pharmacia-ASPET Award for Experimental Therapeutics, 2013
- Invited speaker, Nobel Forum on GPCRs, Stockholm, June 2003
- NIH Pharmacology (PHRA) Study Section, 1996-2000 (Chair, 1999-2000)
- NIH Molecular and Integrative Signal Transduction (MIST) Study Section, 2007-2010 (Chair)
Committees & Activities
- Journal of Biological Chemistry, 1992-1997
- Molecular Pharmacology, 1992- (Associate Editor 1996-1999)
- Molecular InTERventions, 2000-2012
- Chemical Biology & Drug Discovery, 2006-2010
- NC-IUPHAR Receptor Nomenclature (2001-2015)
National & International Society Committees
- President, ASPET, 2012-2015
- Chair, Molecular Pharmacology Division, ASPET, 1997-2002 (Founding chair, 1997 - 1999)
- IUPHAR Receptor Nomenclature Committee, Vice-Chair for GPCRs
- NIH Director’s New Innovator Awards Panel, 2010
- NCATS X02 Therapeutics Discovery Review, 2012.
Full list of articles at MSU Scholars
- FBXO44-Mediated Degradation of RGS2 Protein Uniquely Depends on a Cullin 4B/DDB1 Complex. Sjögren B, Swaney S, Neubig RR. PLoS One. 2015 10:e0123581. PMID: 25970626
- Selectivity and Anti-Parkinson's Potential of Thiadiazolidinone RGS4 Inhibitors. Blazer LL, Storaska AJ, Jutkiewicz EM, Turner EM, Calcagno M, Wade SM, Wang Q, Huang XP, Traynor JR, Husbands SM, Morari M, Neubig RR. ACS Chem Neurosci. 2015 6:911-9. PMID: 25844489
- 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. Haak AJ, Tsou PS, Amin MA, Ruth JH, Campbell P, Fox DA, Khanna D, Larsen SD, Neubig RR. J Pharmacol Exp Ther. 2014 349:480-6. PMID: 24706986
- Gain-of-function mutation in Gnao1: a murine model of epileptiform encephalopathy (EIEE17)? Kehrl JM, Sahaya K, Dalton HM, Charbeneau RA, Kohut KT, Gilbert K, Pelz MC, Parent J, Neubig RR. Mamm Genome. 2014 25:202-10. PMID: 24700286
- Conformational dynamics of a regulator of G-protein signaling protein reveals a mechanism of allosteric inhibition by a small molecule. Vashisth H, Storaska AJ, Neubig RR, Brooks CL 3rd. ACS Chem Biol. 2013 8:2778-84. PMID: 24093330
- Cardiotonic steroids stabilize regulator of G protein signaling 2 protein levels. Sjögren B, Parra S, Heath LJ, Atkins KB, Xie ZJ, Neubig RR. Mol Pharmacol. 2012 82:500-9 PMID: 22695717
- RGS inhibition at G(alpha)i2 selectively potentiates 5-HT1A-mediated antidepressant effects. Talbot JN, Jutkiewicz EM, Graves SM, Clemans CF, Nicol MR, Mortensen RM, Huang X, Neubig RR, Traynor JR. Proc Natl Acad Sci U S A. 2010 107:11086-91. PMID:20534514