William Christopher Wetsel

William Christopher Wetsel

Associate Professor in Psychiatry and Behavioral Sciences

External Address: 
354 Sands Bldg, Durham, NC 27710
Internal Office Address: 
Box 103203 Med Ctr, Durham, NC 27710
Phone: 
919.684.4574

Overview

RESEARCH INTERESTS
Last Updated: 31 December 1997

My laboratory uses genetically-modified mice to study the roles that certain genes and gene products play in the expression of abnormal neuroendocrine, neurological, and psychiatric responses. Traditionally, an identification of neuroendocrine dysfunction has involved biochemical analyses of hormonal responses, those for neurological disorders have relied upon behavioral and postmortem analyses, and those for psychiatric conditions have depended upon phenomenology. The advent of gene manipulation in mice has permitted specific genes to be targeted for disruption, mutation, and/or overexpression in the whole organism or in selected regions or cells in the nervous and other systems. In this way, primary and secondary effects of a given gene manipulation can be related to various neuroendoctine, neurological, or psychiatric conditions in humans. As the Director of the Mouse Behavioral and Neuroendocrine Analysis Core Facility at Duke University (http://sites.duke.edu/mousebehavioralcore/), we have neurobehaviorally phenotyped many different lines of inbred and mutant mice for investigators at Duke and at other research institutions. As a consequence, we have helped to develop many different mouse genetic models of neuroendocrine and neuropsychiatric illness. Following the development of mouse models, we have worked with various investigators to identify the molecular and cellular basis of the neuroendocrine and/or behavioral abnormalities. We are working also with medicinal chemists and certain pharmacological/biotechnological companies to identify novel compounds that will ameliorate abnormal responses in the mutant mice. Some of these preclinical studies are now forming a basis for clinical trials in humans.

Education & Training

  • Ph.D., Massachusetts Institute of Technology 1983

Selected Grants

Regulation of Cocaine Reward and Reinforcement by MeCP2 awarded by National Institutes of Health (Co Investigator). 2013 to 2017

Functional Selectivity: A Novel Approach for CNS Drug Discovery awarded by University of North Carolina - Chapel Hill (Principal Investigator). 2012 to 2017

STIM1-dependent calcium signaling in neuronal responses to hypoxia and ischemia awarded by National Institutes of Health (Collaborator). 2015 to 2017

The 5-HT theory of depression tested in a naturalistic model of 5-HT deficiency awarded by National Institutes of Health (Co Investigator). 2006 to 2017

Optimizing Lead 5-HT2C Ligands for Use in the Treatment of Schizoprenia awarded by (Principal Investigator). 2013 to 2015

Novel high-throughput screening for modifiers of TorsinA pathology awarded by National Institutes of Health (Collaborator). 2013 to 2015

Amphetamine-Induced Transcriptional Plasticity in Striatal GABAergic Interneurons awarded by National Institutes of Health (Co Investigator). 2012 to 2015

Prevention of Temporal Lobe Epilepsy awarded by National Institutes of Health (Collaborator). 2012 to 2014

Regulation of response to chronic antidepressant treatment by MeCP2 awarded by National Institutes of Health (Co Investigator). 2012 to 2014

Pages

Wang, Xiaoming, et al. “Altered mGluR5-Homer scaffolds and corticostriatal connectivity in a Shank3 complete knockout model of autism..” Nat Commun, vol. 7, May 2016. Pubmed, doi:10.1038/ncomms11459. Full Text Open Access Copy

Urban, Daniel J., et al. “Elucidation of The Behavioral Program and Neuronal Network Encoded by Dorsal Raphe Serotonergic Neurons..” Neuropsychopharmacology, vol. 41, no. 5, Apr. 2016, pp. 1404–15. Pubmed, doi:10.1038/npp.2015.293. Full Text

Bao, Xuhui, et al. “Preclinical toxicity evaluation of a novel immunotoxin, D2C7-(scdsFv)-PE38KDEL, administered via intracerebral convection-enhanced delivery in rats..” Invest New Drugs, vol. 34, no. 2, Apr. 2016, pp. 149–58. Pubmed, doi:10.1007/s10637-015-0318-3. Full Text

Matak, Pavle, et al. “Disrupted iron homeostasis causes dopaminergic neurodegeneration in mice..” Proc Natl Acad Sci U S A, vol. 113, no. 13, Mar. 2016, pp. 3428–35. Pubmed, doi:10.1073/pnas.1519473113. Full Text

Park, Su M., et al. “Effects of β-Arrestin-Biased Dopamine D2 Receptor Ligands on Schizophrenia-Like Behavior in Hypoglutamatergic Mice..” Neuropsychopharmacology, vol. 41, no. 3, Feb. 2016, pp. 704–15. Pubmed, doi:10.1038/npp.2015.196. Full Text

Cheng, Jianjun, et al. “Further Advances in Optimizing (2-Phenylcyclopropyl)methylamines as Novel Serotonin 2C Agonists: Effects on Hyperlocomotion, Prepulse Inhibition, and Cognition Models..” J Med Chem, vol. 59, no. 2, Jan. 2016, pp. 578–91. Pubmed, doi:10.1021/acs.jmedchem.5b01153. Full Text

Farrell, Martilias S., et al. “In Vitro and In Vivo Characterization of the Alkaloid Nuciferine..” Plos One, vol. 11, no. 3, 2016. Pubmed, doi:10.1371/journal.pone.0150602. Full Text

Nagy, Eniko, et al. “Reproduction and Growth in a Murine Model of Early Life-Onset Inflammatory Bowel Disease..” Plos One, vol. 11, no. 4, 2016. Pubmed, doi:10.1371/journal.pone.0152764. Full Text Open Access Copy

Wu, Chia-Lung, et al. “Dietary fatty acid content regulates wound repair and the pathogenesis of osteoarthritis following joint injury..” Ann Rheum Dis, vol. 74, no. 11, Nov. 2015, pp. 2076–83. Pubmed, doi:10.1136/annrheumdis-2014-205601. Full Text

Pages