Scripps Research Joint Appointments

Professor, Dorris Neuroscience Center
Faculty, Kellogg School of Science and Technology

Other Joint Appointments

Adjunct Professor, UCSD
Departments of Pharmacology & Neuroscience

Research Focus

Basic and disease-related research on the neurobiology of lysophospholipid signaling and chromosomal aneuploidy in the nervous system
Our laboratory is focused on understanding the development and function of the mammalian nervous system, with a particular emphasis on understanding molecular mechanisms relevant to human diseases. In part, we are studying the receptor-mediated effects of naturally occurring lysophospholipids, namely lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P). Targeted deletion of cognate G protein-coupled receptors that transduce signals initiated by these lipids has revealed that these receptors are essential for diverse biological functions within the nervous system. Our recent focus has been to further characterize receptor-null mutants using receptor agonists and antagonists. Another area of study involves exploring the extent and consequences of changes in chromosome number or aneuploidy in neural cells. Surprisingly, a significant number of normal brain cells, including those in humans, are aneuploid. Aneuploidy exists in both proliferating cells and postmitotic neurons; it produces genetic mosaicism that is likely unique in detail for each brain. The biological functions of neural aneuploidy in the developing and mature brain may play important roles in apoptosis, cell fate, physiological properties and disease.

Education

B.A., English and Biology, University of Hawaii at Manoa
M.D., Medicine, Stanford University
Ph.D., Neuroscience, Stanford University

Awards & Professional Activities

Editorial Board Member, Journal of Biological Chemistry
Selection Committee, Basil O'Conner Scholars, The March of Dimes
Executive Committee, Neurosciences Program, UCSD

Selected References

Gon, Y., Wood, M.R., Kiosses, W.B., Jo, E., Sanna, M.G., Chun, J., Rosen, H. (2005) S1P3 receptor-induced reorganization of epithelial tight junctions compromises lung barrier integrity and is potentiated by TNF. Proc. Natl. Acad. Sci. USA 102, 9270-5.

Kingsbury, M. A., Friedman, B., McConnell, M. J., Rehen, S. K., Yang, A. H., Kaushal, D., Chun, J.(2005). Aneuploid neurons are functionally active and integrated into brain circuitry. Proc. Natl. Acad. Sci. USA, 102, 6143.

Ye, X., Hama, K., Contos, J.J.A., Anliker., B., Inoue, A., Skinner, M.K., Suzuki, H., Amano, T., Kennedy, G., Arai, H., Aoki, J., Chun, J. (2005). LPA3-mediated lysophosphatidic acid signalling in implantation and embryo spacing. Nature 435, 104.

Rehen, S.K., Yung, Y.C., McCreight, M.P., Yang, A.H., Almeida, B.S.V., Kingsbury, M.A., Cabral, K.M.S., Kaushal, D., McConnell, M.J., Anliker, B., Fontanoz, M., Chun, J. (2005). Constitutional aneuploidy in the normal human brain. J. Neurosci., 25, 2176-2180. (cover art)

Links

PSY: Nature: Brains may be genetic mosaics

Biology Reports Ltd, Faculty of 1000

Marathon of the Mind