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: 27 October 2020

My laboratory uses genetically-modified mice to study the roles that certain genes and gene products play in the presentation of abnormal neuroendocrine, neurological, and psychiatric responses. Traditionally, the 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 use of genetic technologies has allowed specific genes in selected cells and in neural pathways to be related to certain molecular, biochemical, cellular, physiological, and behavioral dysfunctions. As the Director of the Mouse Behavioral and Neuroendocrine Analysis Core Facility at Duke University (http://sites.duke.edu/mousebehavioralcore/), we have phenotyped many different lines of inbred and mutant mice for my own work as well as 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. We are working also with academic medicinal chemists and/or certain pharmacological/biotechnological companies to identify novel compounds that will ameliorate abnormal responses in various mutant mouse models. Some of these preclinical studies have formed a basis for clinical trials in humans.

Education & Training

  • Ph.D., Massachusetts Institute of Technology 1983

Selected Grants

IPA - William Wetsel awarded by National Institutes of Health (Associate Research Professor). 2017 to 2018

Fragile X Phenotypes Modulated by Altered Signaling to the Synaptic Cytoskeleton awarded by National Institutes of Health (Associate Research Professor). 2014 to 2018

Linking ciliary biology to the functional annotation of psychiatric disorders awarded by National Institutes of Health (Co Investigator). 2016 to 2017

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

Effect of two Rugen compounds on Novel Object Phobia in wild type (WT) and SAPAP3 KO mice awarded by Rugen Holdings (Cayman) (Principal Investigator). 2014 to 2017

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

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

Pages

Badea, Alexandra, et al. “The fornix provides multiple biomarkers to characterize circuit disruption in a mouse model of Alzheimer's disease.Neuroimage, vol. 142, Nov. 2016, pp. 498–511. Pubmed, doi:10.1016/j.neuroimage.2016.08.014. Full Text

Ade, Kristen K., et al. “Increased Metabotropic Glutamate Receptor 5 Signaling Underlies Obsessive-Compulsive Disorder-like Behavioral and Striatal Circuit Abnormalities in Mice.Biol Psychiatry, vol. 80, no. 7, Oct. 2016, pp. 522–33. Pubmed, doi:10.1016/j.biopsych.2016.04.023. Full Text

Bhagat, Srishti L., et al. “Mouse model of rare TOR1A variant found in sporadic focal dystonia impairs domains affected in DYT1 dystonia patients and animal models.Neurobiol Dis, vol. 93, Sept. 2016, pp. 137–45. Pubmed, doi:10.1016/j.nbd.2016.05.003. Full Text

Barak, Larry S., et al. “ML314: A Biased Neurotensin Receptor Ligand for Methamphetamine Abuse.Acs Chem Biol, vol. 11, no. 7, July 2016, pp. 1880–90. Pubmed, doi:10.1021/acschembio.6b00291. Full Text

Klein, Rebecca C., et al. “Opposing effects of traumatic brain injury on excitatory synaptic function in the lateral amygdala in the absence and presence of preinjury stress.J Neurosci Res, vol. 94, no. 6, June 2016, pp. 579–89. Pubmed, doi:10.1002/jnr.23702. Full Text

Weitzel, Douglas H., et al. “Neurobehavioral radiation mitigation to standard brain cancer therapy regimens by Mn(III) n-butoxyethylpyridylporphyrin-based redox modifier.Environ Mol Mutagen, vol. 57, no. 5, June 2016, pp. 372–81. Pubmed, doi:10.1002/em.22021. Full Text

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, p. 11459. 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

Pages