Faculty

JEROLD J.M. CHUN

• Professor, Department of Molecular Biology, The Scripps Research Institute
• Adjunct Professor of Pharmacology & Neurosciences - UCSD School of Medicine

TEL: 858-784-7039

FAX: 858-784-7084

email: jchun@ucsd.edu

website: http://www.scripps.edu/mb/chun/

M.D., Ph.D., Stanford University

We have two major projects related primarily to the development and function of the mammalian nervous system, yet with relevance to many other organ systems.

Lysophospholipid Receptor Signaling: Lysophospholipids (LPs) are simple phospholipids that produce a range of cellular responses that can now be attributed to receptor-mediated mechanisms^1,2. Two major examples of LPs are lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P), and multiple, cognate G-protein coupled receptors have been identified, the first through studies of the embryonic brain³. Targeted deletion of these receptors continues to lead to new insights on the physiological significance of this lipid-based signaling system^4-8, revealing previously unknown roles, particularly in the nervous system^9,10.

Aneuploidy, mosaicism and apoptosis: Programmed cell death (PCD) amongst neural progenitor cells (NPCs) has been identified as a prominent feature of embryonic nervous system development^11,12. It occurs within non-synaptic, proliferative zones rather than postmitotic regions, representing a distinct form of PCD compared to classical, synapse-mediated death, and is partially explained by caspase mechanisms¹³. A surprising discovery from studying NPC PCD was the identification of many aneuploid NPCs, some with extreme forms of aneuploidy^14-16. These data demonstrate that many neural cells are genomically non-identical, producing brains that are, in fact, genetic mosaics. Current studies will determine the biological functions of aneuploidy in the brain, including apoptotic roles..

Selected Publications:

1. Fukushima, N., Ishii, I., Contos, J.J., Weiner, J.A. & Chun, J. Lysophospholipid receptors. Annu Rev Pharmacol Toxicol 41, 507-34 (2001).
2. Ishii, I., Fukukshima, N., Ye, X. & Chun, J. Lysophospholipid receptors: signaling and biology. Ann. Rev. Biochem. (2004).
3. Hecht, J.H., Weiner, J.A., Post, S.R. & Chun, J. Ventricular zone gene-1 (vzg-1) encodes a lysophosphatidic acid receptor expressed in neurogenic regions of the developing cerebral cortex. J Cell Biol 135, 1071-83 (1996).
4. Contos, J.J., Fukushima, N., Weiner, J.A., Kaushal, D. & Chun, J. Requirement for the lpA1 lysophosphatidic acid receptor gene in normal suckling behavior. Proc Natl Acad Sci U S A 97, 13384-9 (2000).
5. Contos, J.J. et al. Characterization of lpa(2) (Edg4) and lpa(1)/lpa(2) (Edg2/Edg4) Lysophosphatidic Acid Receptor Knockout Mice: Signaling Deficits without Obvious Phenotypic Abnormality Attributable to lpa(2). Mol Cell Biol 22, 6921-6929 (2002).
6. Kimura, Y. et al. Two novel Xenopus homologs of mammalian LP(A1)/EDG-2 function as lysophosphatidic acid receptors in Xenopus oocytes and mammalian cells. J Biol Chem 276, 15208-15. (2001).
7. Ishii, I. et al. Marked perinatal lethality and cellular signaling deficits in mice null for the two sphingosine 1-phosphate (S1P) receptors, S1P(2)/LP(B2)/EDG-5 and S1P(3)/LP(B3)/EDG-3. J Biol Chem 277, 25152-9 (2002).
8. Yang, A.H., Ishii, I. & Chun, J. In vivo roles of lysophospholipid receptors revealed by gene targeting studies in mice. Biochim Biophys Acta 1582, 197-203 (2002).
9. Fukushima, N., Ye, X. & Chun, J. Neurobiology of lysophosphatidic acid signaling. Neuroscientist 8, 540-50 (2002).
10. Kingsbury, M.A., Rehen, S.K., Contos, J.J., Higgins, C.M. & Chun, J. Non-proliferative effects of lysophosphatidic acid enhance cortical growth and folding. Nat Neurosci 6, 1292-1299 (2003).
11. Blaschke, A.J., Staley, K. & Chun, J. Widespread programmed cell death in proliferative and postmitotic regions of the fetal cerebral cortex. Development 122, 1165-74 (1996).
12. Blaschke, A.J., Weiner, J.A. & Chun, J. Programmed cell death is a universal feature of embryonic and postnatal neuroproliferative regions throughout the central nervous system. J Comp Neurol 396, 39-50 (1998).
13. Pompeiano, M., Blaschke, A.J., Flavell, R.A., Srinivasan, A. & Chun, J. Decreased apoptosis in proliferative and postmitotic regions of the Caspase 3-deficient embryonic central nervous system. J Comp Neurol 423, 1-12 (2000).
14. Rehen, S.K. et al. Chromosomal variation in neurons of the developing and adult mammalian nervous system. Proc Natl Acad Sci U S A 98, 13361-6 (2001).
15. Kaushal, D. et al. Alteration of gene expression by chromosome loss in the postnatal mouse brain. J Neurosci 23, 5599-606 (2003).
16. Yang, A.H. et al. Chromosome segregation defects contribute to aneuploidy in normal neural progenitor cells. J Neurosci 23, 10454-62 (2003).