Roger Cone

Ph.D., Massachusetts Institute of Technology, 1985
Scientist, Vollum Institute
Joint Assistant Professor, Cell and Developmental Biology

Roger Cone and his associates work on the neuroendocrine control of homeostasis. His laboratory is concentrating on the receptors for the proopiomelanocortin (POMC) peptides and the mechanisms by which these receptors regulate a variety of physiological processes, including energy homeostasis, cardiovascular homeostasis, adrenal steroidogenesis, and pigmentation.

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, but also have numerous roles in the central and peripheral nervous systems.

After cloning and characterizing a family of five receptors for ACTH and MSH peptides, the Cone laboratory has more recently focused efforts on defining the role of one of these, the melanocortin-4 receptor (MC4-R), 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 to be an antagonist of the MSH receptor and the hypothalamic MC4-R. Synthetic MC4-R antagonists as well as deletion of the MC4-R in the mouse were then used to demonstrate that the agouti obesity syndrome results from aberrant antagonism or disruption of central MC4-R signalling. These data showed that central POMC neurons exert a tonic inhibitory effect on feeding behavior and energy storage, and current work in the Cone laboratory is focused on 1) identifying the normal hormonal, nutritional, or afferent signals involved in energy homeostasis that are dependent on the POMC circuitry, 2) identifying the effector neurons and molecules downstream of POMC, and 3) understanding the interactions between the POMC circuitry and other known regulators of energy homeostasis, such as leptin.

Boston, B.A., Blaydon, K.M., Varnerin, J., and Cone, R.D. (1997) Independent and additive effects of central proopiomelanocortin and leptin pathways on murine obesity. Science 278:1641-1644.

Chen, W., Kelly, M.A., Optiz-Arraya, X., Thomas, R.E., Low, M.J., and Cone, R.D. (1997) Exocrine gland dysfunction in MC5-R deficient mice: Evidence for coordinated regulation of exocrine gland function by melanocortin peptides. Cell 91:789-798.

Huszar, D., Lynch, C.A., Fairchild-Huntress, V., Dunmore, J.H., Fang, Q., Berkemeier, L.R., Gu, W., Kesterson, R.A., Boston, B.A., Cone, R.D., Smith, F.J., Campfield, L.A., Burn, P., and Lee, F. (1997) Recapitulation of the agouti obesity syndrome in mice lacking the melanocortin-4 receptor. Cell 88:131-141.

Fan, W., Boston, B.A., Kesterson, R.A., Hruby, V.J., and Cone, R.D. (1997) Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature 385:165-168.

Lu, D., Willard, D., Patel, I.R., Kadwell, S., Overton, L., Kost, T., Luther, M., Chen, W., Woychik, P., Wilkison, W.O., and Cone, R.D. (1994) Agouti protein is an antagonist of the melanocyte-stimulating-hormone receptor. Nature 371:799-802.

To contact Dr. Cone directly: cone@ohsu.edu