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Molecular Medicine

Faculty

J. Sutcliffe, Ph.D.

Professor Emeritus
Department of Molecular Medicine
California Campus
gregor@scripps.edu
(858) 784-8064

Research Focus

Molecular Neurobiology

Our laboratory uses genomics-based tools to identify brain-specific proteins and to elucidate their functions. We recently described the hypocretins, two neuroexcitatory peptides expressed in a few thousand neurons of the dorsolateral hypothalamus. The hypocretins modulate the waking state and suppress rapid eye movement (REM) sleep. Disruption of the hypocretin signaling circuitry results in the sleep disorder narcolepsy. In collaboration with Digital Gene Technologies, Inc., we developed an automated, high throughput cDNA display technology called TOGA. We used this technology to study the mechanism of action of antipsychotic medications. Chronic administration of clozapine to rodents causes a significant increase in the accumulation of apolipoprotein D (apoD) in subsets of neurons and glia within the brain. In post-mortem samples of schizophrenic and bipolar subjects, apoD concentrations were significantly elevated over control levels in regions of pathophysiology. There is anatomical overlap in schizophrenia and bipolar disorder, as well as areas that distinguish the disorders. These data suggest a focal compensation that antipsychotic drug regimens augment. The hypothesis that schizophrenia and related illnesses are disorders of lipid metabolism provides an explanation for the diversity of symptoms associated with psychiatric disorders, and a means by which a number of different genetically, or otherwise, determined biochemical deficits could result in behavioral abnormalities. We are using mice carrying knockout mutations in neural genes to elucidate aspects of their functions, including the role of the postsynaptic, calmodulin-binding protein kinase C substrate RC3/neurogranin in postsynaptic neuroplasticity, and the role of the serotonin 5-HT7 receptor in circadian rhythms and thermoregulation.

Education

Ph.D., Biology, Harvard University, 1978

Awards & Professional Activities

Jacobaeus Award, 2001; Burroughs Wellcome Visiting Professor, 2000; Society for Neuroscience Grass Traveling Lecturer, 1998; Tarbox Distinguished Neuroscientist Award, 1985; Director and Chairman of Scientific Advisory Board, Digital Gene Technologies; Council, American Society for Neurochemistry; Editorial Boards: DNA and Cell Biology; Molecular Neurobiology Reviews, Journal of Neuroscience Research, Journal of Molecular Neuroscience, Advances in Neuroscience, Journal of Neurochemistry

Selected References

Thomas, E.A., Dean, B., Pavey, G., Sutcliffe JG. Increased CNS levels of apolipoprotein D in schizophrenic and bipolar subjects: implications for the pathophysiology of psychiatric disorders. Proc. Natl. Acad. Sci. U S A 98:4066-4071, 2001.

Sutcliffe, J.G. Open-system approaches to gene expression in the CNS. J. Neurosci. 21:8306-8309, 2001.

Sutcliffe, J.G., Foye, P.E., Erlander, M.G., Hilbush, B.S., Bodzin, L.J., Durham, J.T., Hasel, K.W. TOGA: an automated parsing technology for analyzing expression of nearly all genes. Proc. Natl. Acad. Sci. U S A 97:1976-1981, 2000.

Sutcliffe, J.G., de Lecea, L. The hypocretins: integrators of the arousal set point. Nature Reviews Neurosci. 3:339-349

Molecular Medicine Seminar Series

CA Faculty

Asahara, Hiroshi
Balch, William E.
Boddy, Michael
Buxbaum, Joel
Catz, Sergio
Conti, Bruno
Cravatt, Benjamin
D'Lima, Darryl
DerMardirossian, Celine
Deryugina, Elena
Elias, Darlene
Encalada, Sandra
Felding, Brunhilde
Fowler, Velia
Friedlander, Martin
Gerace, Larry
Gottesfeld, Joel
Griffin, John
Hanneken, Anne
Heeb, Mary Jo
Henderson, Scott
Hoch, James
Joazeiro, Claudio
Johnson, Eric
Kanaji, Taisuke
Kay, Steve
Kelly, Jeffery
Koziol, James
Lamia, Katja
Lazzerini Denchi, Eros
Lipton, Stuart
Loring, Jeanne F.
Loskutoff, David
Lotz, Martin
Makarenkova, Helen P.
Mc Millan, Robert
Miles, Lindsey
Milner, Richard
Modena, Brian
Mosnier, Laurent
Paulson, James C.
Perego, Marta
Petrascheck, Michael
Pollard, Kenneth Michael
Quigley, James P.
Reed, Steven
Roberts, Edward
Rosen, Hugh
Ruggeri, Zaverio
Russell, Paul
Saez, Enrique
Smider, Vaughn
Srinivasan, Supriya
Steinhubl, Steven
Sutcliffe, J.
Tan, Eng
Topol, Eric
Vanderklish, Peter
Vogt, Peter K.
Waalen, Jill
Wiseman, Luke
Wittenberg, Curt
Wolan, Dennis W.
Wu, Peng
Wu, Xiaohua
Yang, Xiang-Lei
Yates III, John


FL Faculty

Bohn, Laura M.
Cameron, Michael
Duckett, Derek
Gill, Matt
Griffin, Patrick
Hansen, Scott
Kamenecka, Theodore
Kissil, Joseph
Luo, Junli
McDonald, Patricia
Miller, Courtney
Niedernhofer, Laura
Phinney, Donald G.
Robbins, Paul
Scampavia, Louis
Schimmel, Paul
Smith, Roy
Spicer, Timothy


Affiliated Faculty

Cline, Hollis
Kojetin, Douglas
Lairson, Luke
Paegel, Brian
Rumbaugh, Gavin
Shen, Ben
Solt, Laura A
Su, Andrew
Wu, Chunlei


Adjunct Faculty