William Christopher Wetsel, Ph.D.

Associate Professor in Psychiatry and Behavioral Sciences

Department:
Psychiatry and Behavioral Sciences

Division:
Medical Psychology

Email:
wetse001mcdukeedu

Mailing Address:
BOX 3497, DUMC
DURHAM, NC 27710

Telephone:
919-684-4574

Training:
Ph.D., Massachusetts Institute of Technology

Last Updated:
November 13, 2000

Research Interests:
RESEARCH INTERESTS
Last Updated:  31 December 1997

My laboratory is interested in three different aspects of neuronal and behavioral function.  In the first, we are interested in developing animal models of neuropsychiatric disease.  Some of these diseases in humans are associated with alterations in catecholamine homeostasis, particularly dopamine.  Recently, Dr. Marc Caron at Duke University has developed mice that have either the dopamine or the norepinephrine transporters genetically disrupted.  We are presently conducting behavioral, hormonal, and neurochemical studies with these mice.  Preliminary evidence indicates that the dopamine transporter knockout mice exhibit many of the characteristics of human patients suffering from schizophrenia and/or attention-deficit, hypersentivity disorder .
Another interest of my lab involves the role of peptides in neural and endocrine function.  Peptides are involved in controlling a wide variety of responses that include appetite regulation, stress and depression, thermogenesis, and reproduction. All peptides are first biosynthesized as precursor proteins that have to be processed to become bioactive.  Upon secretion, bioactivity of a given peptide is regulated by certain peptide degrading enzymes.  My lab has identified several processing and degrading enzymes that can regulate the bioactivity of corticotropin-releasing hormone, thyrotropin-releasing hormone, neuropeptide Y, luteinizing hormone-releasing hormone, and opiate peptides.  We are presently developing cell culture and transgenic mouse models to more clearly dissect the roles of these various enzymes in neuronal, endocrine, and behavioral function.  Preliminary evidence from my lab suggests that obesity, diabetes, and fertility are dependent upon the activities of these enzymes.
A final area of interest involves the roles that lipids and their target proteins (e.g., receptors, enzymes) play in signal transduction pathways in neural and endocrine cells.  My lab has found that certain lipids are important in conveying information to and from neurons and glia.  For instance, metabolites of arachidonic acid can activate cannabinoid and eicosanoid receptors, and protein kinase C.  Preliminary evidence from my lab indicates that some of these lipids can modulate and amplify a number of neural, endocrine, and behavioral responses.  Endogenous production of anandamide may affect cannabinoid receptor signaling and tolerance to marihuana.  Alterations in the levels of hippocampal protein kinase C can affect learning and memory and it may underlie the changes in memory that occur with aging.

Publications:
1999 -- 5. Gainetdinov, R. R., Wetsel, W.C., Jones, S.R., Levin, E.D., Jaber, M., and Caron, M.G.: Role of serotonin in the paradoxical calming effect of psychostimulants on hyperactivity. Science 283: 397-401, 1999.

1997 -- 3. Colombo, P.J., Wetsel, W.C., and Gallagher, M.: Spatial memory is related to hippocampal subcellular concentrations of calcium-dependent protein kinase C isoforms in young and aged rats. Proceedings of the National Academy of Sciences (USA), 94: 14195-14199, 1997.

1997 -- 4. Boss, R., Fumagalli, F., Jaber, M., Giros, B., Gainetdinov, R.R., Wetsel, W. C., Missale, C. and Caron, M.G.: Anterior pituitary hypoplasia and dwarfism in mice lacking the dopamine transporter. Neuron 19: 127-138, 1997.

1995 -- 1. Wetsel, W.C., Liposits, Z., Seidah, N. G. and Collins, S.: Expression of candidate pro-LHRH processing enzymes in rat hypothalamus and an immortalized hypothalamic neuronal cell line. Neuroendocrinology 62: 166-177, 1995.

1995 -- 2. Wetsel, W.C.: Immortalized hypothalamic LHRH neurons: a new tool for dissecting the molecular and cellular basis of LHRH physiology. Cellular and Molecular Neurobiology 15: 43-78, 1995