Wai Leong TAM

Adjunct Assistant Professor

Affiliations

Adjunct Assistant Professor, Department of Biochemistry, Yong Loo Lin School of Medicine, NUS.
Principal Investigator, Genome Institute of Singapore, A*STAR.
Principal Associate, Cancer Science Institute of Singapore, National University of Singapore.

Biodata

Wai Leong TAM received his Bachelor’s degree from the NUS in 2003. He began his research career as a graduate student in the laboratory of Prof. Bing Lim at the Genome Institute of Singapore, where he worked on uncovering the bases for the pluripotency of embryonic stem cells and induced pluripotent stem cells. He was awarded his PhD in 2008 and continued in the same lab for a short postdoctoral stint. In 2009, Wai Leong began his postdoctoral training under the mentorship of Prof. Robert Weinberg at the Whitehead Institute in MIT, where he concentrated on understanding breast cancer stem cell biology and cancer metastasis. He joined GIS as a Principal Investigator in 2014, and his lab currently focuses on uncovering and interrogating the emerging paradigms of cancer stem cells, and designing rational strategies to specifically target cancer stem cells as a part of cancer therapy. In 2015, he was awarded the Singapore NRF Fellowship.

Education

Degree and Institution Year(s)
Ph.D., Stem Cell Biology, Genome Institute of Singapore 2008
B.Sc. (First Class Honors), Biology, National University of Singapore 2003

Professional Experience

Position and Institute Year(s)
Adjunct Assistant Professor, Department of Biochemistry, Yong Loo Lin School of Medicine, NUS 2015–present
Singapore National Research Foundation Fellow, NRF 2015–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, Genome Institute of Singapore, A*STAR 2008-2009

Research Interest

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?

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.

  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. Chen, X., Iliopoulos, D., Zhang, Q., Tang, Q., Greenblatt, M.B., Hatziapostolou, M., Lim, E., Tam, W.L., Ni, M., Chen, Y., Mai, J., Shen, H., Hu, D.Z., Adoro, S., Hu, B., Song, M., Landis, M.D., Ferrar, m., Brown, M., Chang, J.C., Liu, X.S., and Glimcher, L.H. (2014). XBP1 promotes human triple negative breast cancer by controlling the hypoxia response. Nature. 508:103-107.

  6. Katz, Y., Li, F., Lambert, N., Sokol, E., Tam, W.L., Cheng, A., Airoldi, E.M., Lengner, C.J., Gupta, P.B., Yu, Z., Jaenisch, R. and Burge, C.B. (2014). Musashi Proteins are Post-transcriptional Regulators of the Epithelial-luminal Cell State. eLife. Nov 7.

  7. Tam, W.L. and Weinberg, R.A. (2013). The epigenetics of epithelial-mesenchymal plasticity in cancer. Nature Medicine. 19:1438-1449

  8. 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

  9. Guo, W., Keckesova, Z., Donaher, J.L., Shibue, T., Reinhardt, F., Itzkovitz, S., Bell, G., Tam, W.L., Tischler, V., Mani, S.A., van Oudenaarden, A., and Weinberg, R.A. (2011). Slug and Sox9 cooperatively determine the mammary stem cell state. Cell. 148:1015-1028

  10. 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

  11. Zhang, J., Liu, X., Datta, A., Govindarajan, K.R., Tam, W.L., George J., Liu, E.T., Murthy, K.R., Lim, B., Miller, L.D. (2009). Integrative clinico-genomic analysis identifies RAB11FIP1 as a novel breast cancer oncogene. Journal of Clinical Investigation. 119(8):2171-2183

  12. 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

  13. 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

  14. Tay, Y.M.S.*, Tam, W.L.*, Ang, Y.S.*, Gaughwin, P.M., Wang, W.J., Liu, R., George, J., Ng, H.H., Miranda, K.C., Perera, R.J., Lufkin, T., Rigoutsos, I., Thomson, A. and Lim, B. (2008). MicroRNA-134 modulates the differentiation of mouse embryonic stem cells. Stem Cells. 26: 17-29.
    *Equal contributions

  15. Tam W.L., Ang Y.S. and Lim B. (2007). The molecular basis of ageing in stem cells. Mechanisms of Ageing and Development. 128: 137-148

  16. 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

  17. Miranda K.C., Huynh T., Ang, Y.S., Tay Y., Tam, W.L., Thomson A.M., Lim B. and Rigoutsos I. (2006). A pattern-based method for the identification of microRNA-target sites and their corresponding RNA/RNA complexes. Cell. 126: 1203-1217

  18. Kocabas, A., Crosby, J., Ross, P.J., Otu, H.H., Beyhan, Z., Kaplan, H., Tam, W.L., Rosa, G.J.M., Halgren, R.G., Lim, B., Fernandez, E. and Cibelli, J.B. (2006). Transcriptome Analysis of the Human Oocyte. Proceedings of the National Academy of Sciences U S A. 103: 14027-14032

  19. Chew, J.L., Loh, Y.H., Zhang, W., Chen, X., Tam, W.L., Yeap, L.S., Li, P., Ang, Y.S., Lim, B., Robson, P. and Ng, H.H. (2005). Reciprocal regulation of OCT4 and SOX2 genes via Oct4/Sox2 complex in embryonic stem cells. Molecular and Cellular Biology. 25: 6031-6046