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RESEARCH FOCUS
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Our long term goal is to gain a full molecular understanding of the developmental and evolutionary origins of the mammalian blastocyst. In the mouse, the implanting blastocyst consists of three cell types that develop over the 4.5 days following fertilization. This involves the reprogramming of the highly differentiated oocyte and sperm genomes into the pluripotent cells of the epiblast/inner cell mass (ICM; the source of all cell types of the embryo proper and of the embryonic stem (ES) cell), the trophectoderm (TE; the stem cells of the embryonic components of the placenta), and the primitive endoderm (PrE; the extraembryonic endoderm precursors). We are determining the precise temporal and spatial patterns of all genes expressed in the mouse preimplantation conceptus. In addition, we are studying the transcriptional regulation of genes specific to each of the three cell types to begin to understand the genetic regulatory network that underlies blastocyst biology. In addition to this genetic control of early development we are also interested in the role of epigenetics (ie. histone modifications) in these first cell lineage decisions. A second aspect of our research is to use comparative genomics strategies to identify the molecular changes that have lead to this uniquely mammalian stage of development. This historical perspective will not only improve our understanding of mammalian early development in itself but also allow us to apply to it, in the proper context, the wealth of information available in studies from non-mammalian species. Our model organism, the mouse, provides us with the ability to study these first cellular differentiation events in a whole embryo culture system. This system is well suited for molecular manipulations via traditional mouse genome modifications or through RNAi, and for live cell imaging. Knowledge gained from a clear understanding of the molecular development and evolutionary history of the mammalian blastocyst will be directly applicable to potential and real clinical applications in the fields of stem cell therapy and assisted reproduction.
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EDUCATION
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| 1999-2002 | Postdoctoral Fellow, Division of Cardiology, Children's Hospital of Philadelphia, Philadelphia, PA, USA | | 1992-1998 | Ph.D., Department of Biochemistry, University of Toronto/Hospital for Sick Children, Toronto, ON, Canada | | 1985-1989 | B.Sc.(Hons), University of Guelph, Guelph, ON, Canada. Major: Genetics & Molecular Biology, Minor: Biochemistry |
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PROFESSIONAL APPOINTMENTS
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| 2007- | Group Leader, Genome Institute of Singapore |
| 2002-2007 | Senior Researach Scientist, Genome Institute of Singapore |
| 2003- | Adjunct Assistant Professor, Department of Biological Sciences, National University of Singapore |
| 2004- | Faculty, NUS Graduate School for Integrative Sciences & Engineering, National University of Singapore |
| 1989-1992 | Research Technician, Division of Cardiovascular Research, Hospital for Sick Children, Toronto, ON, Canada |
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HONORS AND AWARDS
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| 2006-2009 | Principal Investigator, Singapore Stem Cell Consortium grant |
| 2006 | Collaboration Development Award (Neuroscience), British High Commission, Singapore |
| 2000 | American Heart Association Postdoctoral Fellowship |
| 2000 | Heart & Stroke Foundation of Canada Postdoctoral Fellowship (declined) |
| 1997 | T-Holder Academic Excellence Award, University of Toronto |
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COMMITTEE AND ADVISORY BOARD
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| 2006- | Institutional Animal Care and Use Committee, Biological Resource Centre, A*Star, Biopolis, Singapore |
| 2003- | Biosafety Management Committee, Genome Institute of Singapore |
| 2005- | Local Review Panel, Singapore National Grid |
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EXTERNAL GRANT
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July 2006 to June 2009 |
Improved Derivations of Human Embryonic Stem Cells Via Modelling of the Preimplantation Genetic Regulatory Network by
Singapore Stem Cell Consortium (S$851,100)
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CURRENT PERSONNEL
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Woon Chow Thai (Research Assistant)
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Sun Lili (Research Assistant)
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Wang Chaoyang (Post Doctoral Fellow)
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Audi Tri Harsono (Undergraduate Student)
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Teo Tang Yi Roy (Graduate Student)
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Guo Guoji (Post Doctoral Fellow)
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Luo Wenlong (Post Doctoral Fellow)
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Shan Quah (Research Officer)
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Wishva Herath (Graduate Student)
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George Devasia (Bioinformatics Specialist)
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Tapan Kumar Mistri (Graduate Student)
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Margarette Nani (Graduate Student)
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Mehran Rahmani (Graduate Student)
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Erlyani Bte Abd Hamid (Graduate Student)
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Jameelah Sheik Mohamed (Research Assistant)
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SELECTED PUBLICATIONS
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1. Guo G, Huss M, Tong GQ, Wang C, Li Sun L, Clarke ND, Robson P "Resolution of cell fate decisions revealed by single-cell gene expression analysis from zygote to blastocyst." Dev Cell 2010 Apr 20 ; 18(4) : 675-85
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2. Ralston Amy, Cox Brian J, Nishioka Noriyuki, Sasaki Hiroshi, Chea Evelyn, Rugg-Gunn Peter, Guo Guoji, Robson Paul, Draper Jonathan S, Rossant Janet "Gata3 regulates trophoblast development downstream of Tead4 and in parallel to Cdx2." Development 2010 Feb ; 137(3) : 395-403
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3. Sheik Mohamed Jameelah, Gaughwin Philip Michael, Lim Bing, Robson Paul, Lipovich Leonard "Conserved long noncoding RNAs transcriptionally regulated by Oct4 and Nanog modulate pluripotency in mouse embryonic stem cells." RNA 2010 16:324-37
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4. Yuan Ping, Han Jianyong, Guo Guoji, Orlov Yuriy L, Huss Mikael, Loh Yuin-Han, Yaw Lai-Ping, Robson Paul, Lim Bing, Ng Huck-Hui "Eset partners with Oct4 to restrict extraembryonic trophoblast lineage potential in embryonic stem cells." Genes Dev. 2009 Nov 1 ; 23(21) : 2507-20
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5. Hutchins Andrew P, Robson Paul "Unraveling the human embryonic stem cell phosphoproteome." Cell Stem Cell 2009 Aug 7 ; 5(2) : 126-8
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6. Jedrusik Agnieszka, Parfitt David-Emlyn, Guo Guoji, Skamagki Maria, Grabarek Joanna B, Johnson Martin H, Robson Paul, Zernicka-Goetz Magdalena "Role of Cdx2 and cell polarity in cell allocation and specification of trophectoderm and inner cell mass in the mouse embryo." Genes Dev. 2008 Oct 1 ; 22(19) : 2692-706
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7. Jiang Jianming, Chan Yun-Shen, Loh Yuin-Han, Cai Jun, Tong Guo-Qing, Lim Ching-Aeng, Robson Paul, Zhong Sheng, Ng Huck-Hui "A core Klf circuitry regulates self-renewal of embryonic stem cells." Nat. Cell Biol. 2008 Mar ; 10(3) : 353-60
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8. Zhang Jinqiu, Tam Wai-Leong, Tong Guo Qing, Wu Qiang, Chan Hsiao-Yun, Soh Boon-Seng, Lou Yuefei, Yang Jianchang, Ma Yupo, Chai Li, Ng Huck-Hui, Lufkin Thomas, Robson Paul, Lim Bing "Sall4 modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5f1." Nat. Cell Biol. 2006 Oct ; 8(10) : 1114-23
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9. Loh Yuin-Han, Wu Qiang, Chew Joon-Lin, Vega Vinsensius B, Zhang Weiwei, Chen Xi, Bourque Guillaume, George Joshy, Leong Bernard, Liu Jun, Wong Kee-Yew, Sung Ken W, Lee Charlie W H, Zhao Xiao-Dong, Chiu Kuo-Ping, Lipovich Leonard, Kuznetsov Vladimir A, Robson Paul, Stanton Lawrence W, Wei Chia-Lin, Ruan Yijun, Lim Bing, Ng Huck-Hui "The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells." Nat. Genet. 2006 Apr ; 38(4) : 431-40
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10. Rodda David J, Chew Joon-Lin, Lim Leng-Hiong, Loh Yuin-Han, Wang Bei, Ng Huck-Hui, Robson Paul "Transcriptional regulation of nanog by OCT4 and SOX2." J. Biol. Chem. 2005 Jul 1 ; 280(26) : 24731-7
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COMPLETE PUBLICATION LIST
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