Yi Sun
Assistant Professor
UCLA Intellectual and Developmental Disabilities Research CenterUniversity of California, Los Angeles
Mail Code 733222
NRB, Rm 351
Los Angeles, CA 90024
310-825-9506 (tel)
[email protected]
Biography/Curriculum Vitae:
Research Interests:
Role of the neurogenin gene in cell-fate specification, cell differentiation and survival
Narrative of Current Research Efforts:
The research in the Sun laboratory is aimed at understanding the molecular mechanisms by which cell-fate decisions, cell proliferation and differentiation are controlled in neural stem cells (NSC). 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 neurological disorders.
Both extracellular /environmental factors and cell intrinsic programs influence stem cell proliferation and differentiation. For example, 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. Recently, they 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 the JAK-STAT pathway and the expression of glial genes, resulting in neurogenesis. They also found that DNA methylation is another cell intrinsic factor that also inhibits the JAK-STAT pathway and consequently suppresses astrogliogenesis during the neurogenic period.
Therefore, both neurogenin expression and DNA methylation are part of the molecular mechanism of the biological clock that controls the timing of neuronal and glial differentiation. Future research will focus on elucidating:
- 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
- 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
- how cell intrinsic factors such as neurogenic bHLH factors and DNA methylation modulate the cellular response of neural progenitors to extracellular factors including LIF and BMP. Sun's laboratory is currently developing a method to allow eficient derivation of pure NSC cultures from mouse embryonic stem cells (ES cells).
Major Honors and Awards:
Representative Publications:
Martinowich K, Hattori D, Wu H, Fouse S, He F, Hu Y, Fan G and Sun YE (2003) DNA methylation-related chromatin remodeling in activity-dependent BDNF gene regulation. Science, 302:890-3.
Sun YE, Martinowich K and Ge W (2003) Making and repairing the mammalian brain--signaling toward neurogenesis and gliogenesis. Semin Cell Dev Biol, 14:161-8.
Fan G, Beard C, Chen RZ, Csankovszki G, Sun Y, Siniaia M, Biniszkiewicz D, Bates B, Lee PP, Kuhn R, Trumpp A, Poon C, Wilson CB and Jaenisch R (2001) DNA hypomethylation perturbs the function and survival of CNS neurons in postnatal animals. J Neurosci, 21:788-97.
Fan G, Egles C, Sun Y, Minichiello L, Renger JJ, Klein R, Liu G and Jaenisch R (2000) Knocking the NT4 gene into the BDNF locus rescues BDNF deficient mice and reveals distinct NT4 and BDNF activities. Nat Neurosci, 3:350-7.
Created 7/27/2006 by Evette Mezger
Last modified 8/28/2006 by Dorwin Birt
