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


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

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

Neurovascular dysfunction in delirium superimposed on dementia awarded by National Institutes of Health (Co Investigator). 2017 to 2022

Exploiting Dopamine Receptor Functional Selectivity as an Approach to Treat Parkinson's Symptoms awarded by National Institutes of Health (Co Investigator). 2017 to 2022

Molecular and cellular control of injury-induced astrogenesis awarded by National Institutes of Health (Co Investigator). 2017 to 2022

DART2.0: comprehensive cell type-specific behavioral neuropharmacology awarded by National Institutes of Health (Collaborating Investigator). 2018 to 2021

Targeting microbially-derived juvenile protective factors to resolve neuroinflammation and delirium awarded by National Institutes of Health (Co Investigator). 2019 to 2021

Bioelectronic rescue of cognitive impairment after surgery awarded by National Institutes of Health (Co Investigator). 2018 to 2021


Rodriguiz, R. M., and W. C. Wetsel. “Assessments of cognitive deficits in mutant mice.” Animal Models of Cognitive Impairment, 2006, pp. 223–82.

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.Alzheimers Dement, vol. 16, no. 5, May 2020, pp. 734–49. Pubmed, 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

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

Pogorelov, Vladimir M., et al. “Postsynaptic Mechanisms Render Syn I/II/III Mice Highly Responsive to Psychostimulants.Int J Neuropsychopharmacol, vol. 22, no. 7, July 2019, pp. 453–65. Pubmed, doi:10.1093/ijnp/pyz019. Full Text

Badea, Alexandra, et al. “Multivariate MR biomarkers better predict cognitive dysfunction in mouse models of Alzheimer's disease.Magn Reson Imaging, vol. 60, July 2019, pp. 52–67. Pubmed, doi:10.1016/j.mri.2019.03.022. Full Text

Shen, Yudao, et al. “D2 Dopamine Receptor G Protein-Biased Partial Agonists Based on Cariprazine.J Med Chem, vol. 62, no. 9, May 2019, pp. 4755–71. Pubmed, doi:10.1021/acs.jmedchem.9b00508. Full Text

Arbogast, Thomas, et al. “Kctd13-deficient mice display short-term memory impairment and sex-dependent genetic interactions.Hum Mol Genet, vol. 28, no. 9, May 2019, pp. 1474–86. Pubmed, doi:10.1093/hmg/ddy436. Full Text