Cheng-Yu Lee, Ph.D.
Lab website: http://www.lsi.umich.edu/facultyresearch/labs/lee
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.
Education and Training
|1996||B.S. with Honors, University of Maryland-College Park, Department of Zoology|
|1996-1999||Graduate Teaching Assistant, Department of Biology, University of Maryland|
|1996-2002||Graduate Research Assistant, Center for Agricultural Biotechnology, University of Maryland Biotechnology Institute, with Dr. Eric H. Baehrecke|
|2002||Ph.D., University of Maryland-College Park, Department of Biology|
|2002-2006||Post-doctoral Research Associate, Institute of Neuroscience, University of Oregon, with Dr. Chris Q. Doe|
Honors & Awards
|2001||Outstanding Graduate Student, University of Maryland Biotechnology Institute|
|2003-2006||Damon Runyon Wintchell Cancer Research Foundation Post-doctoral Research Fellowship|
|2006-2011||Burroughs Wellcome Fund Career Awards in the Biomedical Sciences|
Lee CY, Wendel DP, Reid P, Lam G, Thummel CS, Baehrecke EH. E93 directs steroid-triggered programmed cell death in Drosophila. Mol Cell, 2000 Aug; 6(2):433-443. (PMID 10983989).
Lee CY, Baehrecke EH. Genetic regulation of programmed cell death in Drosophila. Cell Res, 2000 Sep; 10(3):193-204. (PMID 11032171).
Lee CY, Cooksey BA, Baehrecke EH. Steroid regulation of midgut cell death during Drosophila development. Dev Biol, 2002 Oct 1; 250(1):101-111. (PMID 12297099).
Lee CY, Simon CR, Woodard CT, Baehrecke EH. Genetic mechanism for the stage-and tissue-specific regulation of steroid triggered programmed cell death in Drosophila. Dev Biol, 2002 Dec 1; 252(1):138-148. (PMID 12453466).
Lee CY, Clough EA, Yellon P, Teslovich TM, Stephan DA, Baehrecke EH. Genome-wide analyses of steroid- and radiation-triggered programmed cell death in Drosophila. Curr Biol, 2003 Feb 18; 13(4):350-357. (PMID 12593803).
Rolls MM, Albertson R, Shih HP, Lee CY, Doe CQ. Drosophila aPKC regulates cell polarity and cell proliferation in neuroblasts and epithelia. J Cell Biol, 2003 Dec 8; 163(5):1089-1098. (PMID 14657233) PMC 2173607.
Lee CY, Robinson KJ, Doe CQ. Lgl, Pins and aPKC regulate neuroblast self-renewal versus differentiation. Nature, 2006 Feb 2; 439(7076):594-598. (PMID 16357871).
Lee CY, Wilkinson BD, Siegrist SE, Wharton RP, Doe CQ. Brat is a Miranda cargo protein that promotes neuronal differentiation and inhibits neuroblast self-renewal. Dev Cell, 2006 Apr; 10(4):441-449. (PMID 16549393).
Lee CY, Andersen RO, Cabernard C, Manning L, Tran KD, Lanskey MJ, Bashirullah A, Doe CQ. Drosophila Aurora-A kinase inhibits neuroblast self-renewal by regulating aPKC/Numb cortical polarity and spindle orientation. Genes Dev, 2006 Dec 15; 20(24):3464-3474. (PMID 17182871) PMC 1698452.
Martin DN, Balgley B, Dutta S, Chen J, Rudnick P, Cranford J, Kantartzis S, DeVoe DL, Lee C, Baehrecke EH. Proteomic analysis of steroid-triggered autophagic programmed cell death during Drosophila development. Cell Death Differ, 2007 May; 14(5):916-923. (PMID 17256009).
Weng M, Golden KL, Lee CY. dFezf/Earmuff maintains the restricted developmental potential of intermediate neural progenitors in Drosophila. Dev Cell, 2010 Jan 19; 18(1):126-135. (PMID 20152183).
Weng M, Lee CY. Keeping neural progenitor cells on a short leash during Drosophila neurogenesis. Curr Opin Neurobiol, 2011 Feb; 21(1):36-42. (PMID 20952184) PMC 3037426.
Haenfler JM, Kuang C, Lee CY. Cortical aPKC kinase activity distinguishes neural stem cells from progenitor cells by ensuring asymmetric segregation of Numb. Dev Biol, 2012 May 1; 365(1):219-228. (PMID 22394487) PMC 3322243.
Weng M, Haenfler JM, Lee CY. Changes in Notch signaling coordinates maintenance and differentiation of the Drosophila larval optic lobe neuroepithelia. Dev Neurobiol, 2012 Nov; 72(11):1376-1390. (PMID 22038743) PMC 3407541.
Weng M, Komori H, Lee CY. Identification of neural stem cells in the Drosophila larval brain. Methods Mol Biol, 2012; 879:39-46. (PMID 22610552) PMC 3600560.