Currently the SSCC uses its intramural allocation to directly fund five groups comprising 30 scientists. All the groups except one are based at the A*STAR Institute of Medical Biology and focus on embryonic, neural and induced pluripotential stem (IPS) cells. Over the next year (2008) it plans to recruit principal investigators in the areas of epithelial, haemopoietic and/or mesenchymal stem cells. Current senior investigators are listed below :

Biography
Alan Colman is currently a Principal Investigator in the A*STAR Institute of Medical Biology and also Executive Director of the Singapore Stem Cell Consortium. His research will involve the differentiation of human and mouse embryonic or embryonic-like (induced pluripotential stem cells) stem cells that harbor deleterious mutations known in humans to cause distinctive pathological conditions. Neurodegenerative disease will comprise a major focus.

Alan Colman obtained a BA degree in Biochemistry in Oxford (1971) and a PhD under John Gurdon, a pioneer of the field of nuclear transfer, at the MRC Laboratory of Molecular Biology in Cambridge, UK (1974). After a series of academic appointments in Oxford and Warwick Universities, he became Professor of Biochemistry in the University of Birmingham, UK. The focus of his academic career was the area of eukaryotic protein secretion, with a particular emphasis on the use of frog oocytes and eggs as in vivo test tubes.

From 1987 until March 2002, he was research director of the company PPL Therapeutics in Edinburgh, UK. This company specialized in the production of transgenic livestock that produced human therapeutic proteins in their milk. PPL attracted considerable media attention because of its participation, together with the Roslin Institute, in the technique of somatic nuclear transfer. This work led to Dolly, the world's first sheep cloned from an adult somatic cell (1996), Polly and Molly, the first cloned transgenic livestock (1997), Diana and Cupid, the first livestock with targeted genetic changes (2000), Millie et al., the first cloned pigs (2000) and, finally, Austin and crew, the first homozygous alpha-gal-transferase knock-out pigs (2003).

From April 2002 - June 2007, he worked for the Singapore - based company, ES Cell International (ESI), first as its Chief Scientific Officer (April 2002 - February 2005) and then its Chief Executive Officer (February 2005 - June 2007). ESI specialized in the development of human embryonic stem cell-based therapies for the treatment of diabetes and congestive heart failure.

Representative Publications
1. Crook JM, Peura T, Kravets L, Bosman A, Buzzard JJ, Horne R, Hentze H, Dunn NR, Zweigerdt R, Chua F, Upshall A, Colman A (2007) The generation of six clinical-grade human embryonic stem cell lines. Cell Stem Cell, 1:490-494.

2. Colman A and Burley JC (2007) Recycling the abnormal Nature (News and Views) 447 649- 650

3. Graichen R, Hentze H and Colman A (2007) Cell therapy and the safety of embryonic stem cell - derived grafts. Trends in Biotechnology 25 :24-32.

4. Crook JM, Horne R & Colman A (2006) Standard Culture of Human Embryonic Stem Cells, In: Human Embryonic Stem Cells: The Practical Handbook; ed. Sullivan S, Cowan C & Eggan K, John Wiley & Sons, Ltd. pp53-79.

5. Andreia S Bernardo; John Barrow; Colin W Hay; Kenneth McCreath; Alexander J Kind; Angelika E Schnieke; Alan Colman; Alan W Hart; Kevin Docherty (2006) Presence of endocrine and exocrine markers in EGFP positive cells from the developing pancreas of a nestin/EGFP mouse. Molecular and Cellular Endocrinology. 253:14-21.

6. Crook JM, Dunn NR & Colman A (2006) Repressed by a NuRD. Nature Cell Biol. 8(3):212-214.

7. Maitra A, Arking DE, Shivapurkar N, Ikeda M, Stastny V, Kassauei K, Sui G, Cutler DJ, Liu Y, Brimble SN, Noaksson K, Hyllner J, Schulz TC, Zeng X, Freed WJ, Crook J, Abraham S, Colman A, Sartipy P, Matsui S, Carpenter M, Gazdar AF, Rao M, Chakravarti A (2005) Genomic alterations in cultured human embryonic stem cells. Nature Genetics. 37(10):1099-103.

8. Buzzard JJ, Gough NM, Crook JM, & Colman A (2004) Karyotype of human ES cells during extended culture. Nature Biotech. 22(4):381-382.

9. Colman A (2004) Making new beta cells from stem cells. Seminars in Cell and Developmental Biology 15(3):337-45.

10. Yifan Dai, Todd D. Vaught, Jeremy Boone, Shu-Hung Chen, Carol J. Phelps, Suyapa Ball, Jeff A. Monahan, Peter M. Jobst, Ashley E. Lamborn, Jamie L. Cowell-Lucero, Kevin D.Wells, Kenneth J. McCreath, Alan Colman, Irina A. Polejaeva and David L. Ayares (2002) Targeted Disruption of the 1,3-galactosyltransferase Gene in Cloned Pigs. Nature Biotechnology 20 251-255.

Ray Dunn
Principal Investigator, Endodermal Development and Differentiation
mouse embryo, embryonic stem cells, gastrulation, endoderm, pancreas

Email: ray.dunn@imb.a-star.edu.sg

Biography
Dr. Ray Dunn obtained his Ph.D. in Cell Biology in 1999 from Vanderbilt University under the supervision of Brigid Hogan, PhD FRS. His thesis described how the TGFb-related growth factor BMP4 controls primordial germ cell formation in the early mammalian embryo. He then completed a post-doctoral fellowship in the laboratory of Elizabeth Robertson, PhD FRS at Harvard University, where he studied the growth factor Nodal and its intracellular effector proteins Smad2 and Smad3 during early axis formation and early germ layer patterning in the mouse. In 2004, he joined ES Cell International Pte Ltd as a Research Scientist in the Diabetes Group, eventually being named Program Manager in 2005. In July of this year, he was appointed as a Principal Investigator in the Institute for Medical Biology and Singapore Stem Cell consortium.

Representative Publications
1. Crook, J.M., T.T. Peura, L. Kravets, A.G. Bosman, J.J. Buzzard, R. Horne, H. Hentze, N.R. Dunn, R. Zweigerdt, F. Chua, A. Upshall, and A. Colman. 2007. The generation of six clinical-grade human embryonic stem cell lines. Cell Stem Cell 1: 490-494.

2. Phillips, B.P., H. Hentze, W.L. Rust, Q.-P. Chen, H. Chipperfield, E.-K. Tan, S. Abraham, A. Sadasivam, P.L. Soong, S.T. Wang, R. Lim, W. Sun, A. Colman, and N.R. Dunn. 2007. Directed differentiation of human embryonic stem cells into the pancreatic endocrine lineage. Stem Cells Dev 16(4):561-78.

3. Crook, J.M., N.R. Dunn, and A. Colman. 2006. Repressed by a NuRD. Nature Cell Bio 8: 212-214.

4. Rust, W.L., A. Sadasivam, and N.R. Dunn. 2006. Three-dimensional extracellular matrix stimulates gastrulation-like events in human embryoid bodies. Stem Cells Dev 15: 889-904.

5. Vincent, S.D., N.R. Dunn, R. Sciammas, M. Shapiro-Shalef, M.M. Davis, K. Calame, E.K. Bikoff, and E.J. Robertson. 2005. The zinc finger transcriptional repressor Blimp-1/Prdm1 is required for specification of primordial germ cells in the mouse. Development 132: 1315-1325.

6. Dunn, N.R., C.H. Koonce, D.C. Anderson, A. Islam, E.K. Bikoff, and E.J. Robertson. 2005. Mice exclusively expressing the short isoform of Smad2 develop normally and are viable and fertile. Genes Dev 19: 152-163.

7. Chu, G.C., N.R. Dunn, D.C. Anderson, L. Oxburgh, and E.J. Robertson. 2004. Differential requirements for Smad4 in TGFb-dependent patterning of the early mouse embryo. Development 131, 3501-12.

8. Dunn, N.R., S.D. Vincent, L. Oxburgh, E.J. Robertson, and E.K. Bikoff. 2004. Combinatorial activities of Smad2 and Smad3 regulate mesoderm formation and patterning in the mouse embryo. Development 131, 1717-1728.

9. Vincent, S.D., N.R. Dunn, S. Hayashi, D.P. Norris, and E.J. Robertson. 2003. Cell fate decisions within the mouse organizer are governed by graded Nodal signals. Genes Dev 17, 1646-1662.

Robert Zweigerdt
Principal Investigator, Stem Cell Cardiogenesis
cancer cell signalling, tyrosine kinase mutations, polymorphisms in cancer, cancer therapeutics

Email: robert.zweigerdt@imb.a-star.edu.sg

Biography
Robert Zweigerdt received his PhD from the University of Braunschweig in 1998 where he studied skeletal muscle development and transcriptional gene regulation in mouse embryos and in ES cells in Hans Arnold's lab. Following postdoctoral work on transgenic and KO mice (Nkx 2.3, 3.1) he moved from academia to the biotech company Cardion AG, Düsseldorf, Germany. He was managing a gene therapy project on MCP1-induced tissue revascularization and finally headed a cell therapy approach for heart muscle repair. In collaboration with Jürgen Lehman, a pioneer in bioreactor development, and Loren Field, a leading scientist in heart muscle regeneration, Robert was instrumental in developing a process for large scale production of ESC-derived cardiomyocytes. Moving to Peter Wernet, University Hospital Düsseldorf, in 2004 he worked on the cardiomyogenic differentiation of cord blood-derived cells. In October 2005 he became project manager at the Singaporean company ESI and continued his work on the therapeutic application of human ESC-derived cariomyocytes. Since July 2007 he has been a Principal Investigator in the IMB.

Representative Publications
1. Graichen R, Xu XQ, Braam SR, Balakrishnan T, Norfiza S, Sieh S, Soo SY, Tham SC, Mummery C, Colman A, Zweigerdt R, Davidson BP. Enhanced cardiomyogenesis of human embryonic stem cells by a small molecular inhibitor of p38 MAPK. Differentiation. 2007, submitted.

2. Dai W, Field LJ, Rubart M, Reuter S, Hale SL, Zweigerdt R, Graichen RE, Kay GL, Jyrala A, Colman A, Davidson BP, Pera M, Kloner RA. Survival and maturation of human embryonic stem cell-derived cardiomyocytes in rat hearts. JMCC. 2007, in press.

3. Schroeder M, Niebruegge S, Werner A, Willbold E, Burg M, Ruediger M, Field LJ, Lehmann J, Zweigerdt R. Scalable Differentiation and Lineage Selection of mouse Embryonic Stem Cells in a Stirred Bench Scale Bioreactor with Automated Process Control, Biotechnol Bioeng. 2005 Dec 30;92(7):920-33.

4. Zweigerdt R, Burg M, Willbold E, Abts HF, Ruediger M. Generation of confluent cardiomyocyte monolayers derived from embryonic stem cells in suspension. Cytotherapy. 2003;5(5):399-413.

5. Zandstra PW, Bauwens C, Yin T, Liu Q, Schiller H, Zweigerdt R, Pasumarthi KBS, Field LJ. Scalable production of embryonic stem cell derived cardiomyocytes. Tissue Eng. 2003 Aug;9(4):767-78.

6. Zweigerdt R, Braun T, Arnold H.H. Faithful expression of the Myf-5 gene during mouse myogenesis requires distant control regions: a transgene approach using yeast artificial chromosomes. Dev Biol. 1997 Dec 1;192(1):172-80.

Takahiro Nakano
Principal Investigator, Gene Expression in Differentiation
enhancer analysis, embryonic stem cells, neural and glial differntiation, cell-type specification

Email: takahiro.nakano@imb.a-star.edu.sg

Biography
Takahiro Nakano was born in the US and raised in Japan. He obtained his DVM from School of Veterinary Medicine, Osaka Prefecture University, Japan in 1995, and then received a PhD (in Developmental biology) from Kumamoto University Graduate School of Medicine, Japan in 2000. Before joining IMB, he was a Senior Scientist at Q Therapeutics, Inc. (Salt Lake City, USA) where he developed human oligodendrocyte progenitor cell (hOPC)-based therapies for demyelinating diseases. His work included isolation and characterization of hOPCs. He then used these cells to conduct transplantation studies using mouse disease models. Prior to that, Dr. Nakano was a post doctoral research fellow at Cornell University Medical Center (New York, USA). He identified novel Hb9 enhancers that drive gene expression in spinal motor neurons, and used it for the induction and Hb9 enhancer-directed FACS isolation of spinal motor neurons from hES cells. Similarly, he was involved in the induction and Ngn2 enhancer-directed FACS isolation of mesencephalic dopaminergic neurons from hES cells. As a result, he filed three patent applications.

Representative Publications
1. Roy, N. S., Nakano, T., Keyoung, H. M., Carpenter, M., Jiang, L., Kang, J., Rashbaum, W. K., Nedergaard, M., Goldman, S. A.: Induction and Hb9-directed FACS isolation of spinal motor neurons from human embryonic stem cells. (2005) Exp. Neurol. 196(2): 224-234.

2. Nakano, T., Windrem M., Zappavigna V., Goldman, S. A.: Identification of a conserved 125 base-pair Hb9 enhancer that specifies gene expression to spinal motor neurons. (2005) Dev. Biol. 283(2): 474-485.

3. Roy, N. S., Nakano, T., Keyoung, H. M., Carpenter, M., Jiang, L., Kang, J., Rashbaum, W. K., Nedergaard, M., Goldman, S. A.: Telomerase-immortalization of neuronal progenitor cells derived from the human fetal spinal cord. (2004) Nat. Biotechnol. 22(3): 297-305.

4. Nakano, T., Murata, T., Matsuo, I., Aizawa, S.: OTX2 directly interacts with LIM1 and HNF-3beta. (2000) Biochem. Biophys. Res. Comm. 267(1): 64-70.

5. Ikeda, A., Matsumoto, Y., Chang, K. T., Nakano, T., Matsuyama, S., Yamanouchi, K., Ohta, A., Nishihara, M., Takahashi, M.: Different female reproductive phenotypes determined by human growth hormone(hGH) levels in hGH-transgenic rats. (1997) Biol. Reprod. 56(4): 847-851.

Jeremy Crook
Principal Investigator, Stem Cell Disease Models
embryonic and adult stem cells, differentiation, drug discovery, customized stem cells

Email: jeremy.crook@imb.a-star.edu.sg

Biography
Jeremy holds concurrent appointments as a Senior Research Scientist and Group Leader at A*STAR's Institute of Medical Biology (IMB), and Head of the Singapore Stem Cell Bank (SSCB). The SSCB is a centralized repository and global distributor of human stem cell lines for basic and translational research. The bank also provides technical support and educational opportunities through hands-on training in specialist techniques of human embryonic stem cell culture. At IMB, Jeremy's research interests focus on stem cell based disease modeling to investigate disorders of development relating to the human central nervous system (eg. schizophrenia).

Jeremy completed his PhD under a NH&MRC Scholarship in Neuro-chemistry/-pharmacology at the University of Melbourne (1998). He was awarded a Fogarty Medical Research Fellowship to undertake his post-doctoral studies in the Clinical Brain Disorders Branch (CBDB) of the National Institute of Mental Health at the National Institutes of Health (NIH). His time at NIH included a brief posting in the UK under a Welcome Trust Biomedical Research Collaboration Grant as a Visiting Research Fellow with the Department of Psychiatry, Oxford University. In 2001 Jeremy was appointed a Research Fellow in the Department of Otolaryngology, University of Melbourne. In 2002 he joined ES Cell International Pte Ltd (ESI) as a Senior Research Scientist and Project Manager. With the relocation of ESI's Melbourne based activities to Singapore in 2004, Jeremy was appointed Program Manager of Platform Technologies in the company's Biopolis facility. Since joining IMB, Jeremy has established with Dr Alan Colman the Stem Cell Disease Models Laboratory, which involves adult neural and embryonic stem cell based research.

Representative Publications:
1. Crook JM, Peura T, Kravets L, Bosman A, Buzzard JJ, Horne R, Hentze H, Dunn NR, Zweigerdt R, Chua F, Upshall A, Colman A (2007) The generation of six clinical-grade human embryonic stem cell lines. Cell Stem Cell, 1:490-494.

2. Phillips B, Lim R, Teck TT, Rust W, Crook JM (2007) Efficient expansion of clinical-grade human fibroblasts on microcarriers: cells suitable for ex-vivo expansion of clinical-grade hESCs. J of Biotechnol. In Press.

3. Crook JM, Horne R & Colman A (2006) Standard Culture of Human Embryonic Stem Cells, In: Human Embryonic Stem Cells: The Practical Handbook; ed. Sullivan S, Cowan C & Eggan K, John Wiley & Sons, Ltd. pp53-79.

4. Coleman B, Hardman J, Coco A, Epp S, de Silva M, Crook J & Shepherd R (2006) Fate of Embryonic Stem Cells Transplanted Into the Deafened Mammalian Cochlea. Cell Transplantation, 15:369-380.

5. Bibikova M, Chudin E, Wu B, Zhou L, Garcia EW, Liu Y, Shin S, Plaia TW, Auerbach JM, Arking DE, Gonzalez R, Crook J, Davidson B, Schulz TC, Robins A, Khanna A, Sartipy P, Hyllner J, Vanguri P, Savant-Bhonsale S, Smith AK, Chakravarti A, Maitra A, Rao M, Barker DL, Loring JF & Fan JB (2006) Human Embryonic Stem Cells Have a Unique Epigenetic Signature. Genome Research. 16(9):1075-1083.

6. Crook JM, Dunn NR & Colman A (2006) Repressed by a NuRD. Nature Cell Biol. 8(3):212-214.

7. Maitra A, Arking DE, Shivapurkar N, Ikeda M, Stastny V, Kassauei K, Sui G, Cutler DJ, Liu Y, Brimble SN, Noaksson K, Hyllner J, Schulz TC, Zeng X, Freed WJ, Crook J, Abraham S, Colman A, Sartipy P, Matsui S, Carpenter M, Gazdar AF, Rao M, & Chakravarti A (2005) Genomic alterations in cultured human embryonic stem cells. Nature Genetics. 37(10):1099-103.

8. Shepherd RK, Coco A, Epp SB, & Crook JM (2005) Chronic deplorization enhances the trophic effects of brain-derived neurotrophic factor in rescuing auditory neurons following a sensorineural hearing loss. J Comp Neurol. 486(2): 145-158.

9. Buzzard JJ, Gough NM, Crook JM, & Colman A (2004) Karyotype of human ES cells during extended culture. Nature Biotech. 22(4):381-382.

10. Egan MF, Straub RE, Goldberg TE, Yakub I, Callicott JH, Hariri AR, Mattay VS, Bertolino A, Hyde TM, Shannon-Weickert C, Akil M, Crook J, Vakkalanka RK, Balkissoon R, Gibbs RA, Kleinman JE, & Weinberger DR (2004) Variation in GRM3 affects cognition, prefrontal glutamate, and risk for schizophrenia. Proc. Natl. Acad. Sci. USA, 10.1073.

11. Vawter MP, Crook JM, Hyde TM, Kleinman JE, Weinberger DR, Becker KG, & Freed WJ (2002) Microarray analysis of gene expression in the prefrontal cortex in schizophrenia: a preliminary study. Schiz Research. 58:11-20.

Leah Vardy
Principal Investigator, Translational regulation in stem cells
mouse and human embryonic stem cells, differentiation, mRNA translation, RNA binding proteins, miRNAs

Email: leah.vardy@imb.a-star.edu.sg

Biography
Leah Vardy received her Ph.D at the Imperial Cancer Research Fund in London in the laboratory of Takashi Toda in 2001. Her work investigated the role of three microtubule organizing center components in mitotic progression and checkpoint control. In 2002, she started her post doctoral work with Terry Orr-Weaver at the Whitehead Institute in Cambridge, in the US. There she worked with Drosophila to study the mechanisms by which translation of the mitotic cyclins is temporally controlled during oogenesis and in early embryos. In 2007 she was appointed to the IMB and is currently located at the Genome Institute of Singapore. Her research interests lie in understanding the role translational regulation plays in ES cell self renewal and differentiation.

Representative Publications
Vardy L, Orr-Weaver TL.(2007). Regulating translation of maternal messages: multiple repression mechanisms. Trends Cell Biol. Oct 26;

Vardy L, Orr-Weaver TL.(2007). The Drosophila PNG kinase complex regulates the translation of cyclin B.
Dev Cell. Jan;12(1):157-66

Tadros W, Goldman AL, Babak T, Menzies F, Vardy L, Orr-Weaver T, Hughes TR, Westwood JT, Smibert CA, Lipshitz HD. (2007) SMAUG is a major regulator of maternal mRNA destabilization in Drosophila and its translation is activated by the PAN GU kinase. Dev Cell. 2007 Jan;12(1):143-55.

Lee LA, Lee E, Anderson MA, Vardy L, Tahinci E, Ali SM, Kashevsky H, Benasutti M, Kirschner MW, Orr-Weaver TL. (2005) Drosophila genome-scale screen for PAN GU kinase substrates identifies Mat89Bb as a cell cycle regulator. Dev Cell. Mar;8(3):435-42.

Vardy L, Fujita A, Toda T.(2002) The gamma-tubulin complex protein Alp4 provides a link between the metaphase checkpoint and cytokinesis in fission yeast. Genes Cells. Apr;7(4):365-73.

Vardy L, Toda T. (2000) The fission yeast gamma-tubulin complex is required in G(1) phase and is a component of the spindle assembly checkpoint. EMBO J. Nov 15;19(22):6098-111.