William Christopher Wetsel
Associate Professor in Psychiatry and Behavioral Sciences
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.
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