TAM Wai Leong

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


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.


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?

Lab Members

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  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

Honors & Awards

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