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Jerold Chun, M.D., Ph.D

Professor
Department of Molecular and Cellular Neuroscience
California Campus
Laboratory Website
jchun@scripps.edu
(858) 784-8410

Scripps Research Joint Appointments

Professor, Dorris Neuroscience Center
Faculty, Graduate Program

Other Joint Appointments

Adjunct Professor, UCSD
Departments of Pharmacology & Neuroscience

Research Focus

We are exploring new ways to understand the brain and diseases that affect it.  Both basic science and clinically relevant studies with therapeutic potential are being pursued using cutting-edge approaches, in two areas of investigation. 

Lysophospholipid (LP) receptor signaling focuses on receptor mechanisms, physiological actions and pathophysiological consequences of a growing family of cell surface LP receptors.  A rich range of biology has been identified, and current studies are pursuing basic neurobiology with particular relevance to Hydrocephalus that involves lysophosphatidic acid (LPA) receptors, and Multiple Sclerosis (MS) that involves sphingosine 1-phosphate (S1P) receptors.  

Genomic Mosaicism (GM) in the brain explores single brain cells from the same person that can have distinct genomes, resulting in GM.  The first-identified form, mosaic aneuploidies, continue to be studied and represent a harbinger for other GM forms of DNA content variation (DCV) that include somatic copy number variants (CNVs) and various structural variants (SVs).  Efforts to understand the forms, organization, and functional consequences of GM – including its impact on brain development, alterations by the environment, and its involvement in pathology such as Alzheimer’s disease and other brain disorders – are currently being investigated by single-cell genomic and transcriptomic approaches.

Education

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

Awards & Professional Activities

Awards
• Killam Lecturer, Montreal Neurological Institute • Journal of Lipid Research Lecturer, Keystone Symposium on Bioactive Lipids: Biochemistry and Diseases, Kyoto, Japan • Chancellor’s Award for Excellence in Neuroscience, LSU Medical School • Independent Scientist Award • First Award • Basil O'Connor Scholar (March of Dimes Birth Defects Foundation), UCSD • Klingenstein Fellow in the Neurosciences, UCSD • Alfred P. Sloan Research Fellow, UCSD • Helen Hay Whitney Fellow, Whitehead Institute for Biomedical Research • Trainee, Medical Scientist Training Program (MSTP), Stanford University School of Medicine • Grass Fellowship, Cold Spring Harbor Laboratory course in Molecular and Cellular Neurobiology • Dean prize, outstanding senior thesis in the natural sciences, Univ. Hawaii • B.A. with high honors in English and Biology, University of Hawaii, Manoa

Professional Activities
• Editorial Board, Journal of Lipid Research • Member, Next Generation and Science Educator Awards Selection Committee, Society for Neuroscience • Reviewer, Scientific and Medical Review Committee, Hydrocephalus Association • Reviewer, Scripps Translational Science Institute Pilot Awards Program • Reviewer, Swiss MS Society • Reviewer, MS Research Australia (MSRA) • Reviewer, French Multiple Sclerosis Society (ARSEP) • Reviewer, BSF (United States-Isreal Binational Science Foundation) • Reviewer, The Wellcome Trust/DBT India Alliance • Chair, Hydrocephalus Association Review Panel • Reviewer, Italian Multiple Sclerosis Society (FISM) • Member, Board of Prostaglandins and Other Lipid Mediators • Reviewer, NCI Discovery and Development Special Emphasis Panel P01 • Member, College of CSR Reviewers, NIH • Reviewer, NIMH Sensitive Period RFA • Reviewer, NCI, Discovery, Development, and Diagnosis P01 • Editorial Board, Eye and Brain • Reviewer, NIH ARRA Challenge Grants in Health and Science Research • Reviewer, NIMH ARRA Autism RFA • Co-Chair, Novartis FTY Mechanism of Action Advisory Board • Reviewer, Special Emphasis Panel, Support of Competitive Research (SCORE) Awards, NIGMS • Reviewer, Cancer Research, UK • Editorial Advisory Board, Current Pharmaceutical Design • Editorial Board Member, Open Neuroscience (ON) Journal • Associate Editor, “Prostaglandin and Lipid Mediators,” Bentham Science Pub • Reviewer, Deutsche Forschungsgemeinschaft (DFG), Germany • Reviewer, The Wellcome Trust, UK • Byrd Alzheimer’s Reviewer • Chairman, External Advisory Committee, RCMI/NINDS University of Hawaii • Regular Member, NIH MBPP study section • March of Dimes, Basil O’Connor Scholars Committee • External Reviewer, Biotechnology and Biological Sciences Research Council (BBRC), UK • External reviewer, The Netherlands Organisation for Health Research and Development • External reviewer, Genome British Columbia • Scientific Advisory Committee, Special Neuroscience Research Program (NINDS, University of Hawaii) • External Reviewer, Sass Foundation • Editorial Board Member, Journal of Biological Chemistry • Permanent Member, MDCN-6, NIH • Editorial Board, Journal of Molecular Medicine • External reviewer, Human Frontier Sciences Program • External Advisory Committee, Research Centers in Minority Institutions (RCMI, NCRR/NIH supported), University of Hawaii • External consultant, University of Hawaii School of Medicine • Reviewer, Alzheimer’s Disease Association • Ad hoc Member, MDCN-6, NIH • NIMH Special Emphasis Panel • Permanent Member, NIMH Molecular, Cellular and Developmental Neuroscience • Ad Hoc Reviewer, NSF

Selected References

Chun JJM, Nakamura MJ, Shatz CJ.  Transient cells of the developing mammalian telencephalon are peptide-immunoreactive neurons.  Nature 1987;325:617-620.

Chun JJM, Shatz CJ.  Redistribution of synaptic vesicle antigens is correlated with the disappearance of a transient synaptic zone in the developing cerebral cortex.  Neuron 1988;1:297-310.

Turka LA, Schatz DG, Oettinger MA, Chun JJM, Gorka C, Lee K, McCormack WT, Thompson CB.  Thymocyte expression of the recombination activating genes RAG-1 and RAG-2 can be terminated by T-cell receptor stimulation in vitro.  Science 1991;253:778-781. 

Blaschke AJ, Staley K, Chun J.  Widespread programmed cell death in proliferative and postmitotic regions of the fetal cerebral cortex.  Development 1996;122:1165-1174 (see comment in Neuron 1996;16:693).

Hecht JH, Weiner JA, Post SR, 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 1996;135:1071-1083.

Fukushima N, Kimura Y, Chun J.  A single receptor encoded by vzg-1/lpa1/edg-2 couples to G-proteins and mediates multiple cellular responses to lysophosphatidic acid (LPA).  Proc Natl Acad Sci USA 1998;95:6151-6156.

Weiner JA, Chun J.  Schwann cell survival mediated by the signaling phospholipid lysophosphatidic acid.  Proc Natl Acad Sci 1999;96:5233-5238.

Contos JJA, Fukushima N, Weiner JA, Kaushal D, Chun J.  Requirement for the lpA1 lysophosphatidic acid receptor gene in normal suckling behavior.  Proc Natl Acad Sci USA 2000;97:13384-13389.

Rehen SK, McConnell MJ, Kaushal D, Kingsbury MA, Yang AH, Chun J.  Chromosomal variation in neurons of the developing and adult mammalian nervous system. Proc Natl Acad Sci USA, 2001;98:13361-13366.

Kingsbury MA, Rehen SK, Contos JJA, Higgins C, Chun J.  Non-proliferative effects of lysophosphatidic acid enhance cortical growth and folding.  Nature Neurosci 2003;6:1292-1299.  (See also News & Views).

Inoue M, Rashid H, Ryousuke Fujita R, Contos JJA, Chun J, Ueda H.  Initiation of neuropathic pain requires lysophosphatidic acid receptor signaling.  Nature Med 2004;10:712-718.

Kingsbury MA, Friedman B, McConnell M J, Rehen S K, Yang AH, Kaushal D, Chun J. Aneuploid neurons are functionally active and integrated into brain circuitry. Proc Natl Acad Sci USA 2005;102:6143-6147.  

Barbeito L, Chun J, Binder LI, Neto VM, Perry G, Scazzochio C, Violini G.  The end of a Chilean institute. Science 2005;308:792-793.

Rehen SK, Yung YC, McCreight MP, Yang AH, Almeida BSV, Kingsbury MA, Cabral KMS, Kaushal D, McConnell MJ, Anliker B, Fontanoz M, Chun J. Constitutional aneuploidy in the normal human brain. J Neurosci 2005;25:2176-2180. (cover art)

Ye X, Hama K, Contos JJA, Anliker B, Inoue A, Skinner MK, Suzuki H, Amano T, Kennedy G, Arai H, Aoki J, Chun J. LPA3-mediated lysophosphatidic acid signalling in implantation and embryo spacing. Nature 2005;435:104-108.

Chun J.  The sources of a lipid conundrum.  Science 2007;316:208-210.

Tager AM, LaCamera P, Shea BS, Campanella GK, Selman M, Zhao Z, Polosukhin Z, Wain J, Karimi-Shah BA, Kim ND, Hart WK, Pardo A, Blackwell TS, Xu Y, Chun J, Luster AD. The lysophosphatidic acid receptor LPA1 links pulmonary fibrosis to lung injury by mediating fibroblast recruitment and vascular leak. Nat Med 2008;14(1):45-54.

Niessen F, Schaffner F, Furlan-Freguia C, Pawlinski R, Bhattacharjee G, Chun J, Derian CK, Andrade-Gordon P, Rosen H, Ruf W.  Dendritic cell PAR1-S1P3 signalling couples coagulation and inflammation.  Nature 2008;452(7187):654-658.

Westra JW, Peterson SE, Yung YC, Mutoh T, Barral S, Chun J.  Aneuploid mosaicism in the developing and adult cerebellar cortex.  J Comp Neurol 2008 507(6):1944-1951.

Trimbuch T, Beed P, Vogt J, Schuchmann S, Maier N, Kintscher M, Breustedt J, Schuelke M, Streu N, Kieselmann O, Brunk I, Laube G, Strauss U, Battefeld A, Wende H, Birchmeier C, Wiese S, Sendtner M, Kawabe H, Kishimoto-Suga M, Brose N, Baumgart J, Geist B, Aoki J, Savaskan NE, Brauer AU, Chun J, Ninnemann O, Schmitz D, Nitsch R.  Synaptic PRG-1 modulates excitatory transmission via lipid phosphate-mediated signaling.  Cell 2009;138(6):1222-1235.

Westra JW, Barral S, Chun J.  A reevaluation of tetraploidy in the Alzheimer’s disease brain.  Neurodegen Dis 2009;6(5-6):221-229.

Choi JW, Gardell SE, Herr DR, Rivera R, Lee CW, Noguchi K, Teo ST, Yung YC, Lu M, Kennedy G, Chun J.  FTY720 (fingolimod) efficacy in an animal model of multiple sclerosis requires astrocyte sphingosine 1-phosphate receptor (S1P1) modulation. Proc Natl Acad Sci USA 2011;108(2):751-756. 

Zhou Z, Subramanian P, Sevilmis G, Globke B, Soehnlein O, Karshovska E, Megens R, Heyll K, Chun J, Saulnier-Blache JS, Reinholz M, van Zandvoort M, Weber C, Schober A.  Lipoprotein-derived lysophosphatidic acid promotes atherosclerosis by releasing CXCL1 from the endothelium.  Cell Metab 2011;13(5):592-600.

Herr KJ, Herr DR, Lee CW, Noguchi K, Chun J.  Stereotyped fetal brain disorganization is induced by hypoxia and requires lysophosphatidic acid receptor 1 (LPA1) signaling.  Proc Natl Acad Sci USA 2011;108(37):15444-15449.

Yung YC, Mutoh T, Lin ME, Noguchi K, Rivera RR, Choi JW, Kingsbury MA, Chun J.  Lysophosphatidic acid signaling may initiate fetal hydrocephalus.  Sci Transl Med 2011;3:99ra87.  (See also McAllister JP. Getting to the root of hydrocephalus. Sci Transl Med 2011;3:99fs4)

Lin ME, Rivera RR, Chun J.  Targeted deletion of LPA5 identifies novel roles for lysophosphatidic acid signaling in development of neuropathic pain.  J Biol Chem 2012;287(21):17608-17617.

Peterson SE, Yang AH, Bushman DM, Westra JW, Yung YC, Barral S, Mutoh T, Rehen SK, Chun J.  Aneuploid cells are differentially susceptible to caspase-mediated death during embryonic cerebral cortical development.  J Neurosci 2012;32(46):16213-16222.

Anliker B, Choi JW, Lin ME, Gardell SE, Rivera R, Kennedy G, Chun J.  Lysophosphatidic acid (LPA) and its receptor, LPA1, influence embryonic Schwann cell migration, myelination, and cell-to-axon segregation. Glia 2013;61(12):2009-2022.

Herr DR, Lee CW, Wang W, Ware A, Rivera R, Chun J.  Sphingosine 1-phosphate receptors are essential mediators of eyelid closure during embryonic development.  J Biol Chem 2013;288(41):29882-29889.

Gole J, Gore A, Richards A, Chiu YJ, Fung HL, Bushman D, Chiang HI, Chun J, Lo YH, Zhang K. Massively parallel polymerase cloning and genome sequencing of single cells using nanoliter microwells.  Nature Biotechnol 2013;31(12):1126-1132.

Links

Brains May be Genetic Mosaics

Dorris Neuroscience Center

Marathon of the Mind