Stem cells are precursor cells capable of generating virtually any mature cell types (differentiation) found within the tissue where these stem cells reside over a prolonged period of time or in response to injury. Therefore, stem cells need to maintain their stemness (self-renewal) extensively to prevent the stem cell population from becoming depleted; consequently, a balance between self-renewal and differentiation by stem cells is of paramount importance. We use fruit fly neural stem cells (neuroblasts) as a model to study how self-renewal vs. differentiation because fly neuroblasts always divide unequally to self-renew a neuroblast and to generate an immature daughter cell called ganglion mother cell (GMC), which divides once to generate two mature neurons or glia. Asymmetric cell division allowed fly larval brains to maintain a steady population of 100 neuroblasts per brain lobe while generating thousands of neurons. Mutants that are defective in self-renewal are predicted to exhibit premature loss of neuroblasts (<100) whereas mutants that self-renew excessively are predicted to show an expansion in neuroblasts (>100). Consistent with this hypothesis, I recently demonstrated that atypical Protein Kinase C (aPKC) is a potent inducer of neuroblast self-renewal. We currently combine genetic, biochemical, and genomic approaches to identify the downstream targets of aPKC that promote neuroblast self-renewal. In addition, I previously demonstrated that the transcription factor Prospero (Pros) was asymmetrically partitioned into GMCs, where Pros functions to trigger differentiation for generation of mature cells. We presently employ combination of genomic and bioinformatic approaches to identify the targets of Pros required for activation of GMC differentiation. In parallel, we continue functional analysis of the additional self-renewal defective or differentiation defective mutants that I identified during my post-doctoral study in order to identify genes responsible for the mutant phenotype. Finally, we will apply the insight gained from studying genes that regulate fly neuroblast self-renewal to a clinically relevant vertebrate system such as mouse to test the roles of these fly genes in regulation of vertebrate neural stem cell self-renewal. My long-term goal is identify many signaling pathways expressed in both insect and vertebrate neural stem cells, and contribute to our understanding of neural stem cells in birth defects, regenerative medicine and cancer biology.
Graduate: University of Maryland - College Park, Ph.D., Department of Biology, May 23, 2002
Undergraduate: University of Maryland - College Park, B.S. with Honors, Department of Zoology, May 23, 1996.
8/06 –present Assistant Professor, Center for Stem Cell Biology, Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109
5/02 -7/06: Post-doctoral Research Associate, Institute of Neuroscience, University of Oregon, with Dr. Chris Q. Doe
9/96 - 4/02: Graduate Research Assistant, Center for Agricultural Biotechnology, University of Maryland Biotechnology Institute, with Dr. Eric H. Baehrecke.
9/96 - 5/99: Graduate Teaching Assistant, Department of Biology, University of Maryland.
Honors and Awards
8/06 - 7/11 Burroughs Wellcome Fund Career Awards in the Biomedical Sciences.
8/03 - 7/06 Damon Runyon Wintchell Cancer Research Foundation Post-doctoral Research Fellowship.
12/01 Outstanding Graduate Student, University of Maryland Biotechnology Institute.
Lee, C.-Y., Wilkinson, B, Siegrist, S.E., Wharton, R.P., and Doe, C.Q. (2006) Brain tumor (Brat) is an asymmetrically localized Miranda cargo protein that promotes neuronal differentiation and inhibits neuroblast self-renewal, Dev. Cell, 10(4): 441-449.
Lee, C.-Y., Robinson K.J. and Doe C.Q. (2006) Lgl, Pins and aPKC regulate neuroblast self-renewal versus differentiation, Nature, 439(7076): 594-8.
Rolls M.M., Albertson R., Shih H-P., Lee, C-Y., and Doe C.Q. (2003) Drosophila aPKC regulates cell polarity and cell proliferation in neuroblasts and epithelia. J. Cell Biol, 163(5):1089-98.
Lee C.-Y., Clough E.A., Yellon P., Teslovich, T., Stephan, D.A. and Baehrecke E. H. (2003) Genome-wide analyses of gene expression during steroid- and radiation-triggered programmed cell death. Current Biology, 13(4):350-7.
Lee C.-Y., Cooksey B.A.K., and Baehrecke E.H. (2002a) Steroid regulation of midgut cell death during Drosophila metamorphosis. Developmental Biology, 250(1):101-11.
Lee C.-Y. and Baehrecke E.H. (2001) Steroid regulation of autophagic cell death during Drosophila development. Development 128(8):1443-55.Lee C.-Y. and Baehrecke E.H. (2000) Genetic regulation of programmed cell death in Drosophila. Cell Research 10, 193-204.
Lee C.-Y., Wendel D.P., Reid P., Lam, G., Thummel C.S., and Baehrecke E.H. (2000) E93 directs steroid-triggered programmed cell death in Drosophila. Molecular Cell 6, 433-43.
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