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
Exploiting Biased Agonism at the Ghrelin Receptor (GHSR 1a) for Opioid Addiction awarded by National Institutes of Health (Co-Sponsor). 2020 to 2023
Evaluating cell type-specific non-dopaminergics as a Parkinson's treatment paradigm awarded by National Institutes of Health (Co Investigator). 2018 to 2023
Interrogating the cholinergic basis of opioid reinforcement with subcellular precision awarded by National Institutes of Health (Co Investigator). 2020 to 2023
Heat Shock Factors and Protein Misfolding Disease awarded by National Institutes of Health (Co Investigator). 2018 to 2023
Phase 1 - Biased Agonists as Rapidly Acting Neuropsychiatric Drugs awarded by University of North Carolina - Chapel Hill (Principal Investigator). 2020 to 2022
Neurovascular dysfunction in delirium superimposed on dementia awarded by National Institutes of Health (Co Investigator). 2017 to 2022
Targeting microbially-derived juvenile protective factors to resolve neuroinflammation and delirium awarded by National Institutes of Health (Co Investigator). 2019 to 2022
In Vivo Epigenome Editing with CRISPR-Based Histone Acetyltransferase Transgenic Mice awarded by National Institutes of Health (Associate Research Professor). 2016 to 2022
MECHANISTIC INSIGHTS INTO LSD ACTIONS AT 5-HT2A-SEROTONIN RECEPTORS awarded by University of North Carolina - Chapel Hill (Principal Investigator). 2018 to 2022
Secreted Factors for Zebrafish Spinal Cord Regeneration awarded by National Institutes of Health (Co Investigator). 2017 to 2022
Pages
Rodriguiz, R. M., and W. C. Wetsel. “Assessments of cognitive deficits in mutant mice.” Animal Models of Cognitive Impairment, 2006, pp. 223–82.
White, Allison N., et al. “Genetic deletion of Rgs12 in mice affects serotonin transporter expression and function in vivo and ex vivo.” J Psychopharmacol, vol. 34, no. 12, Dec. 2020, pp. 1393–407. Pubmed, doi:10.1177/0269881120944160. Full Text
Monroe, Tanner O., et al. “PCM1 is necessary for focal ciliary integrity and is a candidate for severe schizophrenia.” Nat Commun, vol. 11, no. 1, Nov. 2020, p. 5903. Pubmed, doi:10.1038/s41467-020-19637-5. Full Text
Fricker, Lloyd D., et al. “Neuropeptidomic Analysis of a Genetically Defined Cell Type in Mouse Brain and Pituitary.” Cell Chem Biol, Nov. 2020. Pubmed, doi:10.1016/j.chembiol.2020.11.003. Full Text
Yu, Shu, et al. “Small ubiquitin-like modifier 2 (SUMO2) is critical for memory processes in mice.” Faseb J, vol. 34, no. 11, Nov. 2020, pp. 14750–67. Pubmed, doi:10.1096/fj.202000850RR. Full Text
Slosky, Lauren M., et al. “β-Arrestin-Biased Allosteric Modulator of NTSR1 Selectively Attenuates Addictive Behaviors.” Cell, vol. 181, no. 6, June 2020, pp. 1364-1379.e14. Pubmed, doi:10.1016/j.cell.2020.04.053. Full Text
Wang, Ping, et al. “Neurovascular and immune mechanisms that regulate postoperative delirium superimposed on dementia.” Alzheimer’S & Dementia : The Journal of the Alzheimer’S Association, vol. 16, no. 5, May 2020, pp. 734–49. Epmc, doi:10.1002/alz.12064. Full Text
Miller-Rhodes, Patrick, et al. “The broad spectrum mixed-lineage kinase 3 inhibitor URMC-099 prevents acute microgliosis and cognitive decline in a mouse model of perioperative neurocognitive disorders.” J Neuroinflammation, vol. 16, no. 1, Oct. 2019, p. 193. Pubmed, doi:10.1186/s12974-019-1582-5. Full Text
Martini, Michael L., et al. “Designing Functionally Selective Noncatechol Dopamine D1 Receptor Agonists with Potent In Vivo Antiparkinsonian Activity.” Acs Chem Neurosci, vol. 10, no. 9, Sept. 2019, pp. 4160–82. Pubmed, doi:10.1021/acschemneuro.9b00410. Full Text
Kritzer, M., et al. “Erratum to ‘Electroconvulsive stimulation increases astrocyte marker GFAP in mouse hippocampus regardless of chronic social defeat stress’ (Brain Stimulation (2019) 12(2) (543), (S1935861X18312105), (10.1016/j.brs.2018.12.791)).” Brain Stimulation, vol. 12, no. 5, Sept. 2019, p. e167. Scopus, doi:10.1016/j.brs.2019.06.008. Full Text
Yang, Rui, et al. “ANK2 autism mutation targeting giant ankyrin-B promotes axon branching and ectopic connectivity.” Proc Natl Acad Sci U S A, vol. 116, no. 30, July 2019, pp. 15262–71. Pubmed, doi:10.1073/pnas.1904348116. Full Text