FACULTY RESEARCH

Faculty List

Yi Eve Sun, Ph.D.

Work Email Address: ysun@mednet.ucla.edu

Lab Number: (310) 267-2197
310-267-2197

Office Phone Number: 310-825-9506
310-825-9506

Work Phone Number: 310-825-9506

Laboratory Address:
635 Charles E. Young Drive South
Los Angeles, CA 90095

Office Address:
NRB 351, 635 Charles E. Young Drive South
Los Angeles, CA 90095

Department / Division Affiliations
Associate Professor, Psychiatry and Biobehavioral Sciences
Associate Professor In-Residence, Semel Institute for Neuroscience and Human Behavior, Molecular & Medical Pharmacology
Member, Brain Research Institute, Eli & Edythe Broad Center of Regenerative Medicine & Stem Cell Research, Gene Regulation GPB Home Area, JCCC Gene Regulation Program Area, Molecular Pharmacology GPB Home Area, Neuroscience GPB Home Area

Research Interests
Neural stem cells (NSC) are immature cells capable of generating all three major cell types in the central nervous system (CNS), neurons, astrocytes, and oligodendrocytes. That they are multipotent and have the ability to self-renew makes NSC good candidates for repairing damage in the CNS and treating neurodegenerative diseases. The research in our laboratory is aimed at understanding the molecular mechanisms by which cell-fate decisions, cell proliferation and differentiation are controlled in NSC. Both extracellular /environmental factors and cell intrinsic programs influence stem cell proliferation and differentiation. For example, our previous studies have shown that the cytokines leukemia inhibitory factor (LIF) and cilliary neurotrophic factor (CNTF), through activation of the JAK (Janus Kinase)/STAT (signal transducers and activators of transcription) signaling pathway, effectively turn on astrocyte specific genes leading NSC to differentiate into astrocytes (Science 1997, 278: 477-483). Recently, we found that a cell intrinsic factor, the basic helix-loop-helix transcription factor neurogenin1, When expressed in these cells, triggers a cascade of neuronal gene activation and at the same time suppresses glial genes, resulting in neurogenesis (Cell 2001, 104: 365-376). Changes in gene expression patterns are key events during cell cycle exit and cell differentiation. Therefore our future research will focus on elucidating, 1. the role of transcription factors such as STATs and neurogenic transcription factors in turning on and off specific gene expression programs related to proliferation and differentiation, and 2. how extracellular factors including LIF, FGF-2, PDGF and BMPs and intracellular signaling pathways (e.g. Ras-MAPkinase, PI3Kinase-AKT and JAK-STAT pathways) regulate the activities of these transcription factors. Currently we are developing a method which will allow us to efficiently derive pure NSC cultures from mouse embryonic stem cells (ES cells). Since these cells are easily genetically modifiable, we will be able to manipulate gene expression through state of the art transgenic or knockout technology in ES cells, then convert the transgenic ES cells into NSC and study the impact of these genes in the proliferation and differentiation of NSC. Understanding the molecular control of cell fate choice will allow us to direct the differentiation of NSC and to genetically engineer NSC (via ES cells) so that they may be suitable in cell replacement therapies for neurological disorders such as Alzheimer's and Parkinson's diseases.


Publications
Zeng Yan, Tan Miao, Kohyama Jun, Sneddon Marissa, Watson Joseph B, Sun Yi E, Xie Cui-Wei Epigenetic enhancement of BDNF signaling rescues synaptic plasticity in aging. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2011; 31(49): 17800-10.
Tao Jifang, Wu Hao, Lin Quan, Wei Weizheng, Lu Xiao-Hong, Cantle Jeffrey P, Ao Yan, Olsen Richard W, Yang X William, Mody Istvan, Sofroniew Michael V, Sun Yi E Deletion of astroglial Dicer causes non-cell-autonomous neuronal dysfunction and degeneration. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2011; 31(22): 8306-19.
Wilburn Brian, Rudnicki Dobrila D, Zhao Jing, Weitz Tara Murphy, Cheng Yin, Gu Xiaofeng, Greiner Erin, Park Chang Sin, Wang Nan, Sopher Bryce L, La Spada Albert R, Osmand Alex, Margolis Russell L, Sun Yi E, Yang X William An antisense CAG repeat transcript at JPH3 locus mediates expanded polyglutamine protein toxicity in Huntington's disease-like 2 mice. Neuron. 2011; 70(3): 427-40.
Wu Hao, D'Alessio Ana C, Ito Shinsuke, Xia Kai, Wang Zhibin, Cui Kairong, Zhao Keji, Sun Yi Eve, Zhang Yi Dual functions of Tet1 in transcriptional regulation in mouse embryonic stem cells. Nature. 2011; 473(7347): 389-93.
Wu Hao, D'Alessio Ana C, Ito Shinsuke, Wang Zhibin, Cui Kairong, Zhao Keji, Sun Yi Eve, Zhang Yi Genome-wide analysis of 5-hydroxymethylcytosine distribution reveals its dual function in transcriptional regulation in mouse embryonic stem cells. Genes & development. 2011; 25(7): 679-84.
Ge, W He, F Kim, KJ Blanchi, B Coskun, V Nguyen, L Wu, X Zhao, J Heng, JI Martinowich, K Tao, J Wu, H Castro, D Sobeih, MM Corfas, G Gleeson, JG Greenberg, ME Guillemot, F Sun, YE Coupling of cell migration with neurogenesis by proneural bHLH factors. PNAS. 2006; 103(5): 1319-1324.
Damelin, M Sun, YE Sodja, VB Bestor, TH Decatenation checkpoint deficiency in stem and progenitor cells. Cancer cell. 2005; 8(6): 479-84.
Ladi, E Nichols, JT Ge, W Miyamoto, A Yao, C Yang, LT Boulter, J Sun, YE Kintner, C Weinmaster, G The divergent DSL ligand Dll3 does not activate Notch signaling but cell autonomously attenuates signaling induced by other DSL ligands. The Journal of cell biology. . 2005; 170(6): 983-92.
Fan, G Martinowich, K Chin, MH He, F Fouse, SD Hutnick, L Hattori, D Ge, W Shen, Y Wu, H ten Hoeve, J Shuai, K Sun, YE DNA methylation controls the timing of astrogliogenesis through regulation of JAK-STAT signaling. Development (Cambridge, England) . 2005; 132(15): 3345-56.
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He, F Ge, W Martinowich, K Becker-Catania, S Coskun, V Zhu, W Wu, H Castro, D Guillemot, F Fan, G de Vellis, J Sun, YE A positive autoregulatory loop of Jak-STAT signaling controls the onset of astrogliogenesis. Nature neuroscience. . 2005; 8(5): 616-25.
Martin, KC Sun, YE To learn better, keep the HAT on. Neuron. . 2004; 42(6): 879-81.
Martinowich, K Hattori, D Wu, H Fouse, S He, F Hu, Y Fan, G Sun, YE DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation. Science. . 2003; 302(5646): 890-3.
Sun, Y Nadal-Vicens, M Misono, S Lin, MZ Zubiaga, A Hua, X Fan, G Greenberg, ME Neurogenin promotes neurogenesis and inhibits glial differentiation by independent mechanisms. Cell. . 2001; 104(3): 365-76.
Fan G, Egles C, Sun Y, Minichiello L, Renger J, Klein R, Liu G, Jaenisch R NT4 and BDNF have Overlapping as well as Distinct Function in vivo. Nature Neuroscience 2000; 3: 350-357.
Gao, Y Sun, Y Frank, KM Dikkes, P Fujiwara, Y Seidl, KJ Sekiguchi, JM Rathbun, GA Swat, W Wang, J Bronson, RT Malynn, BA Bryans, M Zhu, C Chaudhuri, J Davidson, L Ferrini, R Stamato, T Orkin, SH Greenberg, ME Alt, FW A critical role for DNA end-joining proteins in both lymphogenesis and neurogenesis. Cell. . 1998; 95(7): 891-902.
Bonni A*, Sun Y*(equal first authorship), Nadal-Vicens M, Bhatt A, Frank DA, Rozovsky I, Stahl N, Yancopoulos GD, Greenberg ME Regulation of CNS Gliogenesis by JAK-STAT Signaling Pathway. Science 1997; 278: 477-483.
Rao MS, Sun Y, Escary JL, Perreau J, Tresser S, Patterson PH, Zigmond RE, Brulet P, Landis SC Leukemia Inhibitory Factor Mediates an Injury Response but not a target-directed developmental transmitter switch in sympathetic neurons. Neuron 1993; 11: 1175-1185.