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Roger Cone earned his Ph.D. in Biology from the Massachusetts Institute of Technology in 1985. He received his B.A. in Biochemistry from Princeton University. Starting in 1985, Cone was a fellow at the Cold Spring Harbor Laboratory. In 1988, he became an assistant professor in the Division of Molecular Medicine at the New England Medical Center, where he remained until he accepted his appointment to the Vollum in 1990. Cone, a senior scientist in the institute, holds an appointment in the Department of Cell and Developmental Biology in the School of Medicine. Recently, he was appointed director of the OHSU Center for the Study of Weight Regulation and Associated Disorders.
Research Interests
Roger Cone and his associates work on the central control of energy homeostasis. His laboratory concentrates on the central melanocortin system, a complex set of neural circuits they have demonstrated to regulate a variety of physiological processes important to energy homeostasis.
Expressed primarily in the pituitary and the arcuate nucleus of the hypothalamus, POMC is the precursor of at least three families of biologically active peptides: the adrenocorticotropins, the melanotropins, and the endorphins. The first two families, the melanocortins, have well-defined roles in adrenocortical function and pigmentation in addition to several identified actions in the central and peripheral nervous systems.
After cloning and characterizing a family of five receptors for ACTH and MSH peptides, the Cone laboratory focused its efforts on defining the roles of the melanocortin-3 and melanocortin-4 receptors (MC3-R and MC4-R). These receptors are involved in the etiology of the agouti obesity syndrome, one of the five original monogenic obesity syndromes in the mouse. The agouti peptide was demonstrated by Cone and colleagues to be an antagonist of the MSH and the MC4 receptors. Synthetic MC4-R antagonists, as well as deletion of the MC4-R gene in the mouse, were then used to demonstrate that the agouti obesity syndrome results from aberrant antagonism or disruption of central MC4-R signaling. These data showed that central POMC neurons exert a tonic inhibitory effect on feeding behavior and energy storage. Furthermore, neurons expressing MC4-R appear capable of integrating both orexigenic and anorexigenic signals downstream of leptin action, and thus may represent a component of the adipostat. Current work in the laboratory is focused on: 1) identifying the normal hormonal, nutritional, and afferent signals involved in energy homeostasis that depend on the POMC circuitry, 2) identifying the effector neurons and molecules downstream of POMC, 3) developing zebrafish as a model system for the identification of genes involved in the regulation of energy homeostasis.
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Selected Publications
Fan, W., Ellacott, K.L.J., Halatchev, I., Takahashi, K., Yu, P., and Cone, R.D. (2004) Role for the brainstem melanocortin system in CCK-mediated satiety. Nature Neurosci. 7:335-336.
Batterham, R.L., Cowley, M.A., Small, C.J., Herzog, H., Cohen, M.A., Dakin, C.L., Wren, A.M., Kennedy, A.R., Brynes, A.E., Low, M.J., Ghatei, M.A., Cone, R.D., and Bloom, S.R. (2002) Gut hormone PYY3-36 physiologically inhibits food intake. Nature 418:650-653.
Cowley, M.A., Smart, J.L., Cerdan, M.G., Rubinstein, M., Diano, S., Horvath, T.H., Cone, R.D., and Low, M.J. (2001) Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 411:480-484.
Butler, A.W., Marks, D.L., Fan, W., and Cone, R.D. (2001) Melanocortin-4 receptor required for acute homeostatic responses to dietary fat. Nature Neurosci. 4:605-611.
Marks, D.L., Ling, N., and Cone, R.D. (2001) Role of the central melanocortin system in cachexia. Cancer Res. 61:1432-1438.
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