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Ma Laboratory

MaLabSummer2011 

Graduate Student Rotation Projects and Research Assistant Job Available!

Congratulations to Ben for receiving First Prize for his poster presentation at    Northwestern University Center for Genetic Medicine Annual Genetics Group Meeting!




 


Regulation of Motor Neuron and Dopaminergic Neuron Differentiation in Development and Disease

Spinal Motor Neurons and Spinal Muscular Atrophy (SMA).  My laboratory is interested in studying the genetic and epigenetic mechanisms that regulate motor neuron differentiation and why only motor neurons degenerate in spinal muscular atrophy (SMA). To address these questions, we use a combination of genetic, biochemical and cell biological approaches, and utilize genetically modified mice, induced pluripotent stem (iPS) cells reprogrammed from fibroblasts, and embryonic chick neural tubes as model systems. Based on our findings, we hope to develop new therapeutic strategies for treating SMA.

Dopaminergic Neurons and Parkinson's Disease.  Dopaminergic neurons located in the ventral midbrain control movement, emotional behavior and reward mechanisms. Dysfunction of dopaminergic neurons is implicated in Parkinson’s disease, drug addiction, depression, and schizophrenia. Generating dopaminergic neurons from stem cells offers a remarkable opportunity to treat these disorders by replacing sick/dead cells in patients. Stem cell-derived dopaminergic neurons can also serve as model systems to study disease onset, progression and to perform drug screening. To fully utilize these cells, understanding the mechanisms regulating dopaminergic neuron differentiation is crucial. My laboratory is interested in using basic helix-loop-helix transcription factor Neurogenin 2 (Ngn2), which was recently shown to be essential for dopaminergic neuron differentiation, as a molecular handle and entry point to investigate the underlying mechanisms. Using the Ngn2-EGFP knockin mouse line, in which the coding region of Ngn2 was replaced by EGFP to mark all Ngn2-expressing neural progenitors with EGFP, we isolated GFP positive neural progenitors from embryonic mouse ventral midbrain by microdissection and fluorescence-activated cell sorting (FACS), and performed gene expression profiling study using DNA microarray. This leads us to the identification of some novel transcription factors regulating dopaminergic fate specification. We are further investigating the roles of these factors by using genetically modified mice and embryonic chick neural tubes as model systems.

Cancer Stem Cells.  We are also interested in characterizing cancer stem cells from various tumors including medulloblastoma, the most prevalent pediatric tumor, to facilitate the development of therapeutics capable of eliminating them. The traditional model of cancer development considers that tumors arise from a series of sequential mutations. More recently, a new model has been proposed that tissue stem cells undergo mutations that deregulate their self-renewal pathways, leading to tumor formation. We are interested in: 1. Isolating and characterizing cancer stem cells from solid tumors by using genetic cell-lineage tracing approach; 2. Identifying the defects that lead to the development of cancer stem cells; 3. Developing novel models that are capable of interrogating the effect of therapeutics on cancer stem cells.


Selected Publications

Ma, Y. C., Song, M. R., Park, J. P., Ho, H. H., Hu, L., Kurtev, M., Zieg, J., Ma, Q., Pfaff, S. L., and Greenberg, M. E. 2008. Regulation of motor neuron specification by GSK3-mediated phosphorylation of Neurogenin 2. Neuron, 58:65-77.
Neuron Previews on this paper: Lai, H.C. and Johnson, J.E. 2008. Neurogenesis or Neuronal Specification: Phosphorylation Strikes Again! Neuron, 58:3-5.

Datta, S. R., Ranger, A. M., Lin, M. Z., Sturgill, J. F., Ma, Y. C., Cowan, C. W., Dikkes. P., Korsmeyer, S. J., and Greenberg, M. E. 2002. Survival factor-mediated BAD phosphorylation raises the mitochondrial threshold for apoptosis. Developmental Cell, 3(5): 631-43.

Lowry, W. E., Huang, J., Ma, Y. C., Ali, S., Wang, D., Williams, D. M., Okada, M., Cole, P. A., and Huang, X. Y. 2002. Csk, a critical link of protein signals to actin cytoskeletal reorganization. Developmental Cell, 2(6): 733-44.

Zheng, B.*, Ma, Y. C.*, Ostrom, R. S., Insel, P. A., Huang, X. Y. and Farquhar, M. G. 2001. RGS-PX1, a GAP for Gas and sorting nexin in vesicular trafficking. Science, 294:1939-42. (*Equal contribution) 
Science
Perspectives on this paper: Zastrow, M.V. and Mostov, K. 2001. A new thread in an intricate web. Science, 294:1845-47

Ma, Y. C., Huang, J., Ali, S., Lowry, W., and Huang, X. Y. 2000. Src tyrosine kinase is a novel direct effector of G proteins. Cell, 102: 635-646.

Ma, Y. C. and Huang, X. Y. 1998. Identification of the binding site for Gqa on its effector Bruton's tyrosine kinase. Proc. Natl. Acad. Sci., USA 95:12197-12201.


Awards

2011 Whitehall Foundation Scholar Award     The Whitehall Foundation

2009 Schweppe Career Development Award     The Schweppe Foundation

2008 Searle Award
Chicago Community Trust/Searle Leadership Fund in the Life Sciences and Northwestern University

2006 William Randolf Hearst Award
William Randolf Hearst Foundation and Harvard Medical School

2001 Julian R. Rachele Prize for Outstanding Graduate Student Research
Weill Graduate School of Medical Sciences of Cornell University

2001 Robert F. Pitts Prize of Distinguished Research
Weill Medical College of Cornell University

2000 Vincent duVigneaud Award of Excellence
Weill Graduate School of Medical Sciences of Cornell University
 


People

Yong-Chao Ma, Ph.D.     Principal Investigator      

Han Shi      Graduate Student

Lauren Geary     Rotation Graduate Student

Nimrod Miller, Ph.D.     Postdoctoral Fellow

Hehai Wang, Ph.D.     Postdoctoral Fellow

Ben Yang     Research Associate

Monica Yang     Northwestern University Undergraduate Student