TAM Wai Leong

One of the grand challenges for cancer treatment is that current therapeutic strategies to treat tumor are ineffective due to therapy resistance and tumor recurrence that are caused by cancer stem cells (CSCs). The lab addresses this important challenge by integrating the fields of cancer, CSC, targeted therapy, and disease modeling, to translate biological findings about CSCs into innovative, targeted cancer therapies. Advanced multidisciplinary approaches are employed to uncover and interrogate emerging paradigms in CSC biology. This will reveal facets of CSCs that are amendable to rationally designed targeted therapies. High-throughput chemical screening is further utilized to discover potentially useful agents that can eradicate CSCs. In the long-term, the development of these agents will provide novel therapeutic modalities which can be employed as neoadjuvants for cancer treatment.

TAM Wai Leong's Research themes

Research Themes:

1. Energetics: What are the metabolites produced and utilized by CSCs? Why are they uniquely important? How do we exploit the metabolic liabilities of CSCs as therapeutic targets?

2. Synthetic lethality: How do we engineer vulnerabilities into CSCs that will cause them to gain susceptibility to therapy? Can we rewire stemness and differentiation programs in cancer cells?

3. Human tumor modeling: How do we build clinically relevant models for understanding tumor heterogeneity and better model their response to therapy?

4. Non-coding RNAs: Why are non-coding RNAs important for CSCs? What do they do? How do we gain novel mechanistic insights into the function of novel non-coding RNAs?

Selected Publications:

  1. Ye, X., Tam, W.L., Shibue, T., Kaygusuz, Y., Reinhardt, F., Eaton, E. Weinberg, R.A. (2015). Distinct EMT programs control normal mammary stem cells and tumour-initiating cells. Nature. In press. doi: 10.1038/nature14897
  2. Lu, H., Clauser, K.R., Tam, W.L., Frose, J., Reinhardt, F., Baty, C.J., Donnenberg, V.S., Carr, S.A., Weinberg, R.A. (2014). A cancer-stem-cell niche formed by juxtacrine signaling between tumor-associated macrophages and breast cancer stem cells. Nature Cell Biology. 16:1105-17
  3. Shaul, Y.D., Freinkman, E., Comb, W.C., Cantor, J.R., Tam, W.L., Thiru, P., Kim, D., Pacold, M.E., Chen, W.W., Bierie, B., Possemato, R., Weinberg, R.A., Yaffe, M.B. and Sabatini, D.M. (2014). DPYD is a key component of a metabolic gene expression program required for the epithelial-mesenchymal transition. Cell. 158:1-16
  4. Tam, W.L. and Ng, H.H. (2014). Sox2: Masterminding the root of cancer. Cancer Cell. 26:3-5
  5. Tam, W.L. and Weinberg, R.A. (2013). The epigenetics of epithelial-mesenchymal plasticity in cancer. Nature Medicine. 19:1438-1449
  6. Tam, W.L., Lu, H., Buikhuisen, J., Soh, B.S., Lim, E., Reinhardt, F., Wu, Z.J., Krall, J.A., Bierie, B., Guo, W., Chen, X., Liu, X.S., Brown, M., Lim, B. and Weinberg, R.A. (2013). Protein kinase C α is a central signaling node and therapeutic target for breast cancer stem cells. Cancer Cell. 24:347-364
  7. Han, J., Yuan, P., Yang, H., Zhang, J., Soh, B.S., Li, P., Lim, S.L., Cao, S.Y., Tay, J.L., Orlov, Y.L., Lufkin, T., Ng, H.H., Tam, W.L.# and Lim, B.# (2010). Tbx3 improves the germ-line competency of induced pluripotent stem cells. Nature. 463:1096-1100 #Corresponding authors
  8. Lim, C.Y.*, Tam, W.L.*,#, Zhang, J.*, Ang, H.S, Jia, H., Lipovich, L., Ng, H.H., Wei, C.L., Sung, W.K., Robson, P., Yang, H. and Lim, B.# (2008). Sall4 regulates distinct transcription circuitries in different embryo-derived stem cell lineages. Cell Stem Cell. 3:543-554 *Equal contributions; #Corresponding authors
  9. Tam, W.L., Lim, C.Y., Han, J., Zhang, J., Ang, Y.S., Ng, H.H., Yang, H.H. and Lim, B. (2008). Tcf3 regulates embryonic stem cell pluripotency and self-renewal by the repression of Oct4 and multiple lineage pathways. Stem Cells. 26:2019-2031
  10. Zhang, J.*, Tam, W.L.*, Tong, G.*, Wu, Q., Chan, H.Y., Lufkin, T., Soh, B.S., Lou, Y., Ng, H.H., Robson, P and Lim, B. (2006). Sall4 modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Oct4. Nature Cell Biology. 8: 1114-1123 *Equal contributions
Name TAM Wai Leong
Affiliations Principal Investigator, Cancer Science Institute of Singapore, National University of Singapore
Principal Investigator, Genome Institute of Singapore, A*STAR
Adjunct Assistant Professor, Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore
Email tamwl[at]gis.a-star.edu.sg

Education

Institute Degree (if applicable) Year(s)
Genome Institute of Singapore Ph.D 2008
National University of Singapore BSc 2003
Adjunct Assistant Professor, Department of Biochemistry, Yong Loo Lin School of Medicine, NUS 2014 – present
Principal Investigator, Genome Institute of Singapore, A*STAR 2014 – present
Principal Associate, Cancer Science Institute of Singapore, National University of Singapore 2014 – present
Postdoctoral Fellow, Laboratory of Bob Weinberg, Whitehead Institute / MIT 2009 – 2014
Research Fellow, Laboratory of Bing Lim, Genome Institute of Singapore, A*STAR 2008 – 2009

ZHANG Wencai

Research Scientist

Lung cancer stem cell

 

 

 

 

LOO Ser Yue

Postdoctoral Fellow

Breast cancer stem cell and metabolism

 

 

 

 

GAO Bin

Postdoctoral Fellow

Breast cancer stem cell and metastasis

 

 

 

 

YUAN Ju

Postdoctoral Fellow

Lung tumor heterogeneity

 

 

 

 

WANG Zhenxun

Postdoctoral Fellow

Lung cancer stem cell and metabolism

 

 

 

 

Elina PATHAK

Postdoctoral Fellow

Breast tumor heterogeneity

 

 

 

 

Justin TAN

Postdoctoral Fellow

Liver cancer and non-coding RNAs

 

 

 

 

YEE Mei Qi

Research Officer

Breast and lung cancer heterogeneity

 

 

 

 

YEO Zhen Zhen Joanna

Research Officer

Breast and lung cancer stem cell

Singapore NRF Fellow, National Research Foundation, Singapore 2015 – present
MIT Ludwig Center for Molecular Oncology Fellowship 2011 – 2014
A*STAR Postdoctoral Fellowship, A*STAR 2009 – 2011
A*STAR Graduate Scholarship, A*STAR 2003 – 2008
President’s Graduate Fellowship, NUS 2003 – 2006
Vice-Chancellor’s List, NUS 2003
Joanna Wong Gold Medal Award, University Scholars Programme, NUS 2003
Frazer & Neave Book Prize, Faculty of Science, NUS 2002 – 2003
Raffles Prize, Faculty of Science, NUS 2001 – 2003
Dean’s List (every year), NUS 2000 – 2003