George Hess
Professor of Biochemistry

Phone

607-255-4809

Address

Department of Molecular Biology & Genetics
216 Biotechnology Building
Cornell University
Ithaca, NY 14853-2703

Email

Web Sites

Background

George Hess is a Professor of Biochemistry, Molecular and Cell Biology, a member of the National Academy of Sciences, and a Fellow of the American Association for the Advancement of Science. He has been a John S. Guggenheim Fellow, a Fulbright Senior Research Scholar, a NIH Special Fellow, and a recipient of the Alexander von Humboldt Award. He has been a Visiting Fellow at Churchill College, University of Cambridge, and at Yale University; a Visiting Professor at the Universities of Arizona, Hawaii and Pennsylvania, and at MIT; and has twice been a U.S. State Department Cultural Exchange Professor in Europe. He is currently a member of the Editorial Advisory Board of Biochemistry, and an Editor of the Journal of Protein Chemistry. He is a member of the Advisory Board of the Center for Molecular and Behavioral Neuroscience, Universidad del Central Caribe, Puerto Rico. After receiving his doctoral degree at the University of California at Berkeley, he completed his postdoctoral training in the Department of Chemistry at MIT.

Research Description

We are investigating the structure and function of membrane-bound proteins (neurotransmitter receptors) that control and integrate communication between the cells of the nervous system. Malfunction of the receptors is implicated in many diseases of the nervous system, and the receptor proteins are the targets of a large class of clinically important compounds and abused drugs. Until recently investigation of the mechanism of action of these receptor proteins has been hampered by the lack of techniques with adequate time resolution (microseconds to milliseconds). My group has developed new biophysical techniques, most recently a laser-pulse photolysis method, for investigating the receptors in cells isolated from specific areas of the nervous system to fill this gap. When a neurotransmitter binds to the active receptor forms, ion-conducting receptor-channels open, initiating electrical signals that transmit information in the nervous system. Whether or not a signal is transmitted depends on the concentration of open receptor-channels. This in turn depends on the neurotransmitter concentration and the length of time receptors are exposed to it. The immediate goal is to determine quantitative models, on a physiologically relevant time scale, for the chemical kinetic reactions of excitatory and inhibitory neurotransmiter (acetylcholine, gamma-aminobutyric acid, (GABA), glycine, glutamate, N-methyl-D-aspartate (NMDA) and serotonin receptors). This goal has already been achieved with the nicotinic acetylcholine receptor from the electric organ (modified muscle) of certain fish. The eventual aim is to integrate all the available information into a consistent mechanism of signal transmission in the mammalian central nervous system. The chemical mechanism of neurotransmitter receptor-mediated reactions is expected to set limits to the various hypotheses concerning the operation of neuronal circuits and brain function, and to lead to an understanding of the effects of pharmacological agents and abused drugs on receptor function.

An interdisciplinary approach, involving physical and organic chemistry, instrument development, molecular biology, electrophysiology, cellular neurobiology, and computer simulation, is being used to achieve these aims.

Publications

Ramakrishnan, L. and Hess, G. P. (2005) Picrotoxin inhibition mechanism of a gamma-aminobutyric acidA receptor investigated by a laser-pulse photolysis technique Biochemistry 44, 8523-8532.

Shembekar, V. R., Chen, Y., Carpenter, B. K. and Hess, G. P. (2005) A protecting group for carboxylic acids that can be photolysed by visible light. Biochemistry 44, 7107-7014.

Cui, Y., Ulrich, H., and Hess, G. P. (2004) Selection of 2'-fluoro-modified RNA aptamers for alleviation of cocaine and MK-801 inhibition of the nicotinic acetylcholine receptor. J. Membrane Biol. 202, 137-149.

Cui, Y., Rajasethupathy, P., and Hess, G. P. (2004) Selection of stable RNA molecules that can regulate the channel-opening equilibrium of the membrane-bound g –aminobutyric acid receptor. Biochemistry43, 16442-16449.

Chen, Y., Banerjee, A., and Hess, G. P. (2004) Mechanism-based discovery of small molecules that prevent noncompetitive inhibition by cocaine and MK-801 mediated by two different sites on the nicotinic acetylcholine receptor. Biochemistry 43, 10149-10156.

Ramakrishnan, L. and Hess, G. P. (2004) On the mechanism of a mutated and abnormally functioning gamma-aminobutyric acid (A) receptor linked to epilepsy. Biochemistry 43, 7534-7540.

Shembekar, V. R., Carpenter, B. K., Ramachandran, L, and Hess, G. P. (2004) Development of photolabile protecting groups that rapidly release bioactive compounds on photolysis with visible light. Polymer Preprints 45, 8893-894.

Click here to view Dr. Hess' PubMed listings.