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

Behavior and Physiology in Aging awarded by National Institutes of Health (Mentor). 2015 to 2025

Bacteriophage virus-like particle vaccines for fentanyl and heroin overdose awarded by University of New Mexico (Co Investigator). 2021 to 2024

Exploiting Biased Agonism at the Ghrelin Receptor (GHSR 1a) for Opioid Addiction awarded by National Institutes of Health (Co-Sponsor). 2020 to 2023

Interrogating the cholinergic basis of opioid reinforcement with subcellular precision awarded by National Institutes of Health (Co Investigator). 2020 to 2023

Neurovascular dysfunction in delirium superimposed on dementia awarded by National Institutes of Health (Co Investigator). 2017 to 2023

Heat Shock Factors and Protein Misfolding Disease awarded by National Institutes of Health (Co Investigator). 2018 to 2023

Molecular and circuitry mechanism underlying autism behaviors in Shank3 mouse models awarded by Yale University (Principal Investigator). 2019 to 2022

DART2.0: comprehensive cell type-specific behavioral neuropharmacology awarded by National Institutes of Health (Collaborating Investigator). 2018 to 2022

Evaluating cell type-specific non-dopaminergics as a Parkinson's treatment paradigm awarded by National Institutes of Health (Co Investigator). 2021 to 2022

Defining the role of peripheral Adrb3 in chronic pain and inflammation awarded by National Institutes of Health (Co Investigator). 2019 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.

Gross, J. D., et al. “Discovery of a functionally selective ghrelin receptor (GHSR1a) ligand for modulating brain dopamine.Proc Natl Acad Sci U S A, vol. 119, no. 10, Mar. 2022, p. e2112397119. Pubmed, doi:10.1073/pnas.2112397119. Full Text

Jaaro-Peled, Hanna, et al. “Regulation of sensorimotor gating via Disc1/Huntingtin-mediated Bdnf transport in the cortico-striatal circuit.Mol Psychiatry, vol. 27, no. 3, Mar. 2022, pp. 1805–15. Pubmed, doi:10.1038/s41380-021-01389-3. Full Text

Rodriguiz, Ramona M., et al. “LSD-stimulated behaviors in mice require β-arrestin 2 but not β-arrestin 1.Sci Rep, vol. 11, no. 1, Sept. 2021, p. 17690. Pubmed, doi:10.1038/s41598-021-96736-3. Full Text

Dong, Chunyang, et al. “Psychedelic-inspired drug discovery using an engineered biosensor.Cell, vol. 184, no. 10, May 2021, pp. 2779-2792.e18. Pubmed, doi:10.1016/j.cell.2021.03.043. Full Text

Martini, Michael L., et al. “Addition to "Designing Functionally Selective Noncatechol Dopamine D1 Receptor Agonists with Potent In Vivo Antiparkinsonian Activity".Acs Chem Neurosci, vol. 12, no. 8, Apr. 2021, p. 1464. Pubmed, doi:10.1021/acschemneuro.1c00186. Full Text

Fricker, Lloyd D., et al. “Neuropeptidomic Analysis of a Genetically Defined Cell Type in Mouse Brain and Pituitary.Cell Chem Biol, vol. 28, no. 1, Jan. 2021, pp. 105-112.e4. Pubmed, doi:10.1016/j.chembiol.2020.11.003. Full Text

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

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 Open Access Copy

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

Pages