My laboratory has a major interest in the biology of stem cells with a focus on understanding the genetic basis of
1)Hematopoietic stem cell development and functional regulation
2) Growth and Differentiation of Embryonic Stem Cells
3) Generation of stem cells by reporgramming
1)The use of subtractive cDNA library technique led us to the discovery of many novel genes. We have pursued further studies of a number of these genes as a way to reveal novel pathways of cell regulation and function. An important family of genes we are studying is the Ras-related RhoGTPase GTP-binding proteins. We are using biochemical approaches with transplantation and gene-disruption methodologies in murine animals to derive comprehensive information about the function of these genes. We also have a long interest in the use of embryonal stem cells to study stem cell properties of pluripotency, self renewal and differentiation. We are using the ES cells system to study hematopoiesis but we are also very interested in studying the development and differentiation of stem cells of other tissues. We are transferring our knowledge of murine ES cells to begin work with human embryonal stem cells.
Our long term objective is to learn how to control normal stem cell differentiation, using genetic information to facilitate this goal and to accelerate the technology of human cell based therapy. We also seek to identify mutations of genes pertinent to the aberrant development of hematopoietic and other stem cells that cause human diseases and to follow these genes as leads for development of new therapeutic agents.
2)and 3) Embryonic Stem Cell: I curently have a joint appointment at the Genome Institute of Singapore where I am Senior Group Leader for the Stem Cell and Developmental Biology group.
Main focus of research include a) Trancriptome analysis of embryonic and somatic stem cells b )Functional Genomic with semi-high throughput screen c) transcriptome network using ChIP on CHIP and sequencing d) role of microRNA in stem cell development e) molecular basis of reprogramming
Our main objectives are to gain molecular information that will facilitate the controlled differentiation of ES cells for Regenerative Medicine and the generation of new patient-specific ES cells. We are also attempting to establish technology for generating somatic stem cells from non-stem cells.
Layer K, Lin G, Nencioni A, Hu W, Schmucker A, Antov AN, Li X, Takamatsu S, Chevassut T, Dower NA, Stang SL, Beier D, Buhlmann J, Bronson RT, Elkon KB, Stone JC, Parijs LV, and Lim B. Autoimmunity as the Consequence of a Spontaneous mutation in Ras GRP1. Immunity 2003; 19: 243-255
Fortunel NO, Out H, Ng H-H, Chen J, Mu X, Chevassut T, Li X, Joseph M, Bailey C, Hatzfeld JA, Hatzfeld A, Usta F, Vega VB, Long PM, Libermann TA, Lim B. Comment on “Stemness: Transcriptional Profiling of Embryonic and Adult Stem Cells” and “A Stem Cell Molecular Signature” Science 2003; 302:393
Zhang J, Tam W-L, Tong GQ, Wu Q, Chan HY, Soh BS, Lou Y, Yang J, Ma Y, Chai L, Ng HH, Lufkin T, Robson P and Lim B. Sall4 modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5f1. Nature Cell Biology 2006, 10:1113-1123
Tay Y, Zhang J, Thomson AM, Lim B*, Isidore R*. MicroRNAs to Nanog, Oct4 & Sox2 coding regions modulate embryonal stem cell differentiation. Nature 2008 September 17th (Advance Online e-publication) * Co-senior authors
Chin Yan Lim, Wai-Leong Tam, Jinqiu Zhang, Haw Siang Ang, Hui Jia, Leonard Lipovich, Wing Kin Sung, Huck Hui Ng, Chia Lin Wei, Paul Robson, Henry Yang, Bing Lim. Sall4 regulates distinct transcription circuitries in different blastocyst-derived stem cell lineages. Cell Stem Cell 2008 September 18th (Advance Online e-publication)
External Recognition:
Multiple international conferences presentations
1995-present HEM-2 Study Section; Ad Hoc reviewer; 1997-2002 Leukemia and Blood Development Study
American Cancer Society.
1996-present Ad Hoc reviewer, International Human Frontier Science Program;
2005-present Steering Committee, International Regulome Consortium
2006 -present Member, American Association for Cancer Research Human Epigenome Task Force Collaborative Group
Translational Research Grant Award (Leukemia & Lymphoma Society of America) 2002-2005
Editorial Board BLOOD J
Major Collaborative Activities:
Collaboration with Christopher Walsh (BIDMC Neurology)to study neurological phenotype of RhoGTPase genes knockouts.
Collaboration with Dan Tenen (BIDMC, HMS)to study leukemic stem cells
Collaboration with Dr Hava Avraham (BIDMC, HMS) to study embryonic stm cell differentiation
Collaboration with Dr Frank Mckeon (Cell Biology, HMS) to study self renewal of stem cells
Collaboration wiht Li Chi (Brigham Women's, HMS) to study leukemic stem cells
