RESEARCH FOCUS
Transcriptional control of embryonic stem cells
Human embryonic stem (ES) cells provide a unique avenue to study genes that are involved in the earliest stages of differentiation during embryo development. My lab is primarily focused on identification of genes and regulatory pathways that control embryonic stem cell growth and differentiation. We have generated a comprehensive map of the transcriptome from ES cells using genome-wide expression technologies. We have focused particular attention on a set of transcription factors that are uniquely expressed in ES cells and likely play an important role in determining the differentiation status of the ES cells. Functional genomic approaches are being applied to dissect the transcriptional networks that are governed by these known and novel transcription factors, for example REST, Zic3, and Zfp206. The influence these and other transcription factors have on ES cells is then monitored by transcriptional profiling and functional assessment of differentiation capability. Direct targets for key transcription factors are being identified by chromatin precipitation (ChIP) experiments. We are also looking at the epigenetic changes that are mediated by the binding of these transcription factors. The activity of many of these genes is being exploited to drive lineage-specific differentiation of human ES cells and lead to better understanding of the molecular events that underlie early embryonic development and cellular differentiation. Our long-term goal is to derive cell types in vitro that will provide therapeutic utility for certain degenerative diseases in man.
EDUCATION
1985-1989
Postdoctoral Research Fellow University of California San Francisco Laboratory of Dr. J. Michael Bishop
1984
PhD, Biochemistry Activation of the c-myc Oncogene by Chromosomal Translocation in Murine PlasmacytomasState University of New York, Stony Brook Graduate Advisor; Dr. Kenneth Marcu
1979
B.S. Biology (magna cum laude Syracuse University
PROFESSIONAL APPOINTMENTS
2003-date
Deputy Director, Genome Institute of Singapore
2003-date
Assistant Professor(Adjunct), Dept of Biological Sciences, National University of Singapore
2002-date
Senior Group Leader, Stem Cell Genomics, Genome Institute of Singapore
2001-2002
Director, Functional Genomics, Geron Corp., Menlo Park CA, USA
2000-2001
Project Leader, DNA Microarrays, Agilent technologies, Palo Alto CA, USA
1990-2000
Group Leader, Genomics Technology, Scios Inc, Sunnyvale CA, USA
HONORS AND AWARDS
1995
NIH Small Business Innovative Research (SBIR) Grant
1989
1989 Research Award, American Assoc. Cancer Research
1987-1989
NIH Senior Postdoctoral Fellowship
1985-1987
Leukemia Society Postdoctoral Fellowship
1985-1987
Phi Beta Kappa Scholar
SELECTED PUBLICATIONS
1. Buckley Noel J, Johnson Rory, Sun Yuh-Man, Stanton Lawrence W "Is REST a regulator of pluripotency?" Nature 2009 Feb 26 ; 457(7233) : E5-6; discussion E7 Abstract
2. Yu Hong Bing, Kunarso Galih, Hong Felicia Huimei, Stanton Lawrence W "Zfp206, Oct4 and Sox2 are integrated components of a transcriptional regulatory network in embryonic stem cells." J. Biol. Chem. 2009 Sep 9 ; : Abstract
3. Wang Zheng-Xu, Teh Christina Hui-Leng, Chan Caroline Man-Yee, Chu Ci, Rossbach Michael, Kunarso Galih, Allapitchay Tahira Bee, Wong Kee Yew, Stanton Lawrence W "The transcription factor Zfp281 controls embryonic stem cell pluripotency by direct activation and repression of target genes." Stem Cells 2008 Nov ; 26(11) : 2791-9 Abstract
4. Johnson Rory, Teh Christina Hui-leng, Kunarso Galih, Wong Kee Yew, Srinivasan Gopalan, Cooper Megan L, Volta Manuela, Chan Sarah Su-ling, Lipovich Leonard, Pollard Steven M, Karuturi R Krishna Murthy, Wei Chia-lin, Buckley Noel J, Stanton Lawrence W "REST regulates distinct transcriptional networks in embryonic and neural stem cells." PLoS Biol. 2008 Oct 28 ; 6(10) : e256 Abstract
5. Generation of multipotential mesendodermal progenitors from mouse embryonic stem cells via sustained Wnt pathway activation. Bakre MM, Hoi A, Mong JC, Koh YY, Wong KY, and Lawrence W. Stanton. J Biol Chem 282(43), p31703-12 (2007).
6. Genomic and proteomic characterization of embryonic stem cells. Lawrence W. Stanton and Bakre M. Current Opinion in Chemical Biology 11(4), p399-404 (2007).
7. Zfp206 is a transcription factor that controls pluripotency of embryonic stem cells. Wang ZX, Kueh LL, The HL, Rossbach M, Lim L Li P, Wong KY, Lufkin T, Robson P and Lawrence W. Stanton. Stem Cells 25(9), p2173-82 (2007).
8. Zic3 is required for maintenance of pluripotency in embryonic stem cells. Lim LS, Loh YH, Zhang WW, George J, Li Y, Wang Y, Bakre M, Ng HH, and Lawrence W. Stanton. Mol Biol Cell 18(4), p1348-58 (2007).
9. The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells. Loh YH, Wu Q, Chew JL, Vega VB, Zhang WW, Chen X, Bourque G, George J, Leong B, Liu J, Wong KY, Sung KW, Lipovich L, Kuznetsov VA, Robson P, Lawrence W. Stanton, Wei CL, Ruan Y, Lim B, Ng HH. Nature Genetics 38(4), p 431-440 (2006).
10. Brandenberger R, Lebkowski J., Mandalam R., Rao M.S., Guegler K., Fang R., Xu C., Li Y., Fisk G.J., Murage J., Lei S., Zhang S., Wei H, Lawrence STANTON (2004) "Transcriptome characterization elucidates signaling networks that control human embryonic stem cell growth and differentiation." Nature Biotechnology 22 707-716
