Professor of Biochemistry
Publications | Research | Faculty
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.
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.
Click here to view Dr. Hess' PubMed listings.
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. Biochemistry43, 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. Biochemistry43, 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 Preprints45, 8893-894.
Krivoshein, A. V. and Hess, G. P. (2003) Mechanism-based approach to the successful prevention of cocaine inhibition of the neuronal ( a 3 b 4) nicotinic acetylcholine receptor. Biochemistry 43, 481-489.
Banerjee, A., Grewer, C., Ramakrishnan, L., Jäger, J., Gameiro, A., Breitinger, H.-G. A., Gee, K. R., Carpenter , B. K., and Hess, G. P. (2003) Toward the development of new photolabile protecting groups that can rapidly release bioactive compounds upon photolysis with visible light. J. Org. Chem., 68 , 8361-8357.
Hess, G. P., Gameiro, A. M., Schoenfeld, R. C., Chen, Y., Ulrich, H., Nye, J. A., Sit, B., Carroll, F. I., and Ganem, B. (2003) Reversing the action of noncompetitive inhibitors (MK-801 and cocaine) on a protein (nicotinic acetylcholine receptor)-mediated reaction. Biochemistry 42, 6106-6114.
Hess, G. P. (2003) Rapid chemical reaction techniques developed for use in investigations of membrane-bound proteins (neurotransmitter receptors). Biophysical Chemistry100, 493-506.
Wieboldt, R., Ramesh, D., Jabri, E., Karplus, P. A., Carpenter, B. K., and Hess, G. P. (2002) Synthesis and characterization of photolabile o-nitrobenzyl derivatives of urea. J. Org. Chem. 67, 8827-8831.
Li, H. Nowak, L. M., Gee, K. R. and Hess, G. P. (2002) Mechanism of glutamate receptor-channel function in rat hippocampal neurons investigated using the laser-pulse photolysis (LaPP) technique. Biochemistry41, 4753-4759.
Breitinger, H-G. A., Geetha, N., and Hess, G. P. (2001) Inhibition of the serotonin 5-HT 3 receptor by nicotine, cocaine, and fluoxetine investigated by rapid chemical kinetic techniques. Biochemistry40, 8419-8429.
Hess, G. P., Ulrich, A. H., Breitinger, H.-G., Niu, L., Gameiro, A. M., Grewer, C., Srivastava, S., Ippolito, J. E., Lee, S., Jayaraman, V., and Coombs, S. E. (2000) Mechanism-based discovery of ligands that prevent inhibition of the nicotinic acetylcholine receptor by cocaine and MK-801. Proc. Natl. Acad. Sci. USA97, 13895-13900.
Banerjee, A., Carpenter, B. K., and Hess, G. P. (2000) Development of new photolabile protecting groups that can rapidly release bioactive compounds on photolysis with visible light. Polymer Preprints41 (1).
Breitinger, H.-G. A., Wieboldt, R. Ramesh, D., Carpenter, B. K., and Hess, G. P. (2000) Synthesis and characterization of photolabile derivatives of serotonin for chemical kinetic investigations of the serotonin 5-HT 3 receptor. Biochemistry39, 5500-5508.
Grewer, C., Jäger , J., Carpenter, B. K., and Hess, G. P. (2000) A new photolabile precursor of glycine with improved properties: A tool for chemical kinetic investigations of the glycine receptor. Biochemistry39, 2063-2070.
Gee, K. R., Niu, L, Schaper, K., Jayaraman, V., and Hess, G. P. (1999) Synthesis and photochemistry of a photolabile precursor of N-methyl–D-aspartate (NMDA) that is photolyzed in the microsecond time region and is suitable for chemical kinetic investigations of the NMDA receptor. Biochemistry38, 3140-3147.
.Jayaraman, V., Usherwood, P. N. R., and Hess, G. P. (1999) Inhibition of nicotinic acetylcholine receptor by philanthotoxin-343: Kinetic investigations in the microsecond time region using a laser-pulse photolysis technique. Biochemistry38, 11406-11414.
Jayaraman, V., Thiran, S., and Hess, G. P. (1999) How fast does the gamma-aminobutyric acid receptor channel open? Kinetic investigations in the microsecond time region using a laser-pulse photolysis technique. Biochemistry 38, 11372-11378.
Ulrich, H., Ippolito, J. E., Pagan, O. R., Eterovic, V. A., Hann, R. M., Shi, H., Lis, J. T., Eldefrawi, M. E., and Hess, G. P. (1998) In vitro selection of RNA molecules that displace cocaine from the membrane-bound nicotinic receptor. Proc. Natl. Acad. Sci. USA95, 14051-14056
Grewer, C. and Hess, G. P. (1999) On the mechanism of inhibition of a nicotinic acetylcholine receptor by the anticonvulsant MK-801 investigated by laser-pulse photolysis in the microsecond-to-millisecond time region. Biochemistry38, 7837-7846.
Gee, K. R., Niu, L., Schaper, K., Jayaraman, V. and Hess, G. P (1999) Synthesis and photochemistry of a photolabile precursor of N-methyl-D-aspartate (NMDA) suitable for chemical kinetic investigations of the NMDA receptor in the microsecond time region. Biochemistry38, 3140-3147 .
Book chapters
Hess, G. P. (2005) Photochemical release of neurotransmitters – Transient kinetic investigations of membrane-bound receptors on the surface of cells in the microsecond-to-millisecond time region. In Dynamic Studies in Biology Phototriggers, Photoswitches and Caged Biomolecules (Eds. M. Goldner, and R. Givens) Chapter 4.3 (Wiley).
Hess, G. P. Design and application of caged neurotransmitters. In Imaging Living Cells ( Cold Spring Harbor Press, Cold Spring Harbor , NY ) (Eds. R. Yuste, F. Lanni, and A. Konnerth) (1999) pp. 25.1-25.18.
Hess, G. P. (1999) Ligand-activated (caged) biological ligands. The Encyclopedia of Molecular Biology pp. 1385-1391 (Ed. T. E. Creighton) (John Wiley, New York )
Hess, G. P. (1999) Ion transport across biological membranes. Encyclopedia of Physical Science and Technology, Third Edition, Volume 8, 99-108 (Academic Press).
Hess, G. P. and Grewer, C. (1998) Development and application of caged ligands for neurotransmitter receptors in transient kinetic and neuronal circuit mapping studies. Methods in Enzymology291, 443-473.
Gee, K. R., Carpenter, B. K., and Hess, G. P. (1998) Synthesis, photochemistry and biological characterization of photolabile protecting groups for carboxylic acids and neurotransmitters. Methods in Enzymology291, 30-50.