Wai Leong Tam
Postgraduate:
Main Appointment:
Joint Appointments:
Research Fields:
Research Areas:
Research Fields:
- STEMM – Science, Technology, Engineering, Mathematics, Medical Sciences
Research Keywords:
- Cancer Therapeutics
- Cancer Metabolism
- Cancer Stem Cells
- Cancer Metastasis
- Cancer Genomics
Current Appointments:
Brief Description of Research:
The Tam Laboratory seeks to harness functional genomic approaches to gain insights into cancer biology for the development of selective therapeutics against cancer resistance and metastasis. We focus on dissecting two major cell-biological aspects relating to cancer stem cells, resistance, and metastasis: (i) Alterations in cellular energetics; and (ii) Precise control of cell state transitions. We apply advanced methodologies that include genomics, transcriptomics, computational analyses, metabolomics, high-throughput chemical-genetic screens, CRISPR screens, genome engineering, and patient-derived organoids, for building hypotheses that can lead to biological discoveries with clear translational value or intervention potential. The outcome is to achieve novel therapeutic interventions in cancer which are effective and durable.
Total Number of Publications:
Five Representative Publications:
For complete publication list: http://www.ncbi.nlm.nih.gov/pubmed/?term=tam+wl
1. Wang, Z., Yip, L.Y., Lee, J.H.J., Wu, Z., Chew, H.Y., Chong, P.K.W., Teo, C.C., Ang, H.Y.K, Peh, K.L.E., Yuan, J., Choo, L.S.K., Basri, N., Jiang, X., Yu, Q., Hillmer, A., Lim, T.K.H, Takano, A., Tan, E.H., Tan, D.S.W., Ho, Y.S., Lim, B., and Tam, W.L. (2019) Methionine is a metabolic dependency of tumor-initiating cells. Nature Medicine. 25(5):825-837.
2. Tan, J.L., Li, F., Yeo, J.Z., Yong, K.J., Bassal, M.A., Ng, G.H., Lee, M.Y., Leong, C.Y., Tan, H.K., Wu, C.S., Liu, B.H., Chan, T.H., Tan, Z.H., Chan, Y.S., Wang, S., Lim, Z.H., Toh, T.B., Hooi, L., Low, K.N., Ma, S., Kong, N.R., Stein, A.J., Wu, Y., Thangavelu, M.T,, Suzuki, A., Periyasamy, G., Asara, J.M., Dan, Y.Y., Bonney, G.K., Chow, E.K., Lu, G.D., Ng, H.H., Kanagasundaram, Y., Ng, S.B., Tam, W.L.#, Tenen, D.G.#, and Chai, L.# (2019) New High-throughput Screen Identifies Compounds That Reduce Viability Specifically In Liver Cancer Cells That Express High Levels of SALL4 by Inhibiting Oxidative Phosphorylation. Gastroenterology. Aug 22. pii: S0016-5085(19)41242-0. doi: 10.1053/j.gastro.2019.08.022. #Corresponding authors
3. Chen, J., Zhang, T., Yang, H., Teo, A.S.M., Tan, C.Q., Lu, B., Alvarez, J.J.S., Lim, J.Q., Chan, C.X., Faranak, G.S., Takano, A., Nahar, R., Lee, Y.Y., Chua, K.P., Lim, C.H., Koh, T.P.T, Aung, Z.W., Lim, T.K.H, Wilm, A., Liew, A.A., Lau, D.P.X., Kwang, X.L., Toh, C.K., Lim, W.T., Lim, B., Liu, J., Tam, W.L., Tan, E.H., Creasy, C., Tan, D.S.W., Hillmer, A.M., and Zhai, W. (2020) The genomic landscape and ethnic specificity of lung Adenocarcinoma in Asia. Nature Genetics, 52(2):177-186.
4. Goh, J.Y., Feng, M., Wang, W., Oguz, G., Yatim, S.M.J.M., Lee, P.L., Bao, Y., Lim, T.H., Wang, P., Tam, W.L., Kodahl, A.R., Lyng, M.B., Sarma, S., Lin, S.Y., Lezhava, A., Yap, Y.S., Lim, A.S.T., Hoon, D.S.B., Ditzel, H.J., Lee, S.C., Tan, E.Y., Yu, Q. (2017) Chromosome 1q21.3 amplification is a trackable biomarker and actionable target for breast cancer recurrence. Nature Medicine. 23(11):1319-1330.
5. Tan, W.L., Jain, A., Takano, A., Newell, E.W., Iyer, N.G., Lim, W.T., Tan, E.H., Zhai, W., Hillmer, A.M., Tam, W.L., and Tan, D.S.W. (2016) Novel therapeutic targets on the horizon for lung cancer. Lancet Oncology. 17:e347
6. Zhang, W.C., Chin, T.M., Yang, H., Nga, M.N., Lunny, D.P., Lim, E.K.H., Sun, L.L., Pang, Y.H., Leow, Y.N., Malusay, S.R.Y., Lim, P.X.H., Lee, J.Z., Tan, B.J.W., Shyh-Chang, N, Lim, E.H., Lim, W.T., Tan, D.S.W., Tan, E.H., Tai, B.C., Soo, R.A., Tam, W.L.# and Lim, B.# (2016) Tumor-initiating cell-specific miR-1246 and miR-1290 expression converge to promote non-small cell lung cancer progression. Nature Communications. 7:11702. #Corresponding authors
7. Pattabiraman, D.R., Bierie, B., Kober, K., Krall, J., Zill, C., Reinhardt, F., Tam, W.L. and Weinberg, R.A. (2016). cAMP-induced activation of PKA leads to epigenetic reprogramming-mediated mesenchymal-to-epithelial transition and exit from the cancer stem cell state. Science. 351:6277
8. 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. 525:256-60.
9. 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.
10. 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.
11. Tam, W.L. and Ng, H.H. (2014). Sox2: Masterminding the root of cancer. Cancer Cell. 26:3-5.
12. 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.
13. Tam, W.L. and Weinberg, R.A. (2013). The epigenetics of epithelial-mesenchymal plasticity in cancer. Nature Medicine. 19:1438-1449
14. 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
15. 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. (2012). Slug and Sox9 cooperatively determine the mammary stem cell state. Cell. 148:1015-1028
16. 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
17. 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
18. 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
19. 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
20. 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
My Research Videos:
Top 5 Publications:
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Journals Published:
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Wai Leong Tam
Appointments
Education
Research Areas
- Cancer Therapeutics
- Cancer Metabolism
- Cancer Stem Cells
- Cancer Metastasis
- Cancer Genomics
Research Description
The Tam Laboratory seeks to harness functional genomic approaches to gain insights into cancer biology for the development of selective therapeutics against cancer resistance and metastasis. We focus on dissecting two major cell-biological aspects relating to cancer stem cells, resistance, and metastasis: (i) Alterations in cellular energetics; and (ii) Precise control of cell state transitions. We apply advanced methodologies that include genomics, transcriptomics, computational analyses, metabolomics, high-throughput chemical-genetic screens, CRISPR screens, genome engineering, and patient-derived organoids, for building hypotheses that can lead to biological discoveries with clear translational value or intervention potential. The outcome is to achieve novel therapeutic interventions in cancer which are effective and durable.
Research Videos
Selected Publications
For complete publication list: http://www.ncbi.nlm.nih.gov/pubmed/?term=tam+wl
1. Wang, Z., Yip, L.Y., Lee, J.H.J., Wu, Z., Chew, H.Y., Chong, P.K.W., Teo, C.C., Ang, H.Y.K, Peh, K.L.E., Yuan, J., Choo, L.S.K., Basri, N., Jiang, X., Yu, Q., Hillmer, A., Lim, T.K.H, Takano, A., Tan, E.H., Tan, D.S.W., Ho, Y.S., Lim, B., and Tam, W.L. (2019) Methionine is a metabolic dependency of tumor-initiating cells. Nature Medicine. 25(5):825-837.
2. Tan, J.L., Li, F., Yeo, J.Z., Yong, K.J., Bassal, M.A., Ng, G.H., Lee, M.Y., Leong, C.Y., Tan, H.K., Wu, C.S., Liu, B.H., Chan, T.H., Tan, Z.H., Chan, Y.S., Wang, S., Lim, Z.H., Toh, T.B., Hooi, L., Low, K.N., Ma, S., Kong, N.R., Stein, A.J., Wu, Y., Thangavelu, M.T,, Suzuki, A., Periyasamy, G., Asara, J.M., Dan, Y.Y., Bonney, G.K., Chow, E.K., Lu, G.D., Ng, H.H., Kanagasundaram, Y., Ng, S.B., Tam, W.L.#, Tenen, D.G.#, and Chai, L.# (2019) New High-throughput Screen Identifies Compounds That Reduce Viability Specifically In Liver Cancer Cells That Express High Levels of SALL4 by Inhibiting Oxidative Phosphorylation. Gastroenterology. Aug 22. pii: S0016-5085(19)41242-0. doi: 10.1053/j.gastro.2019.08.022. #Corresponding authors
3. Chen, J., Zhang, T., Yang, H., Teo, A.S.M., Tan, C.Q., Lu, B., Alvarez, J.J.S., Lim, J.Q., Chan, C.X., Faranak, G.S., Takano, A., Nahar, R., Lee, Y.Y., Chua, K.P., Lim, C.H., Koh, T.P.T, Aung, Z.W., Lim, T.K.H, Wilm, A., Liew, A.A., Lau, D.P.X., Kwang, X.L., Toh, C.K., Lim, W.T., Lim, B., Liu, J., Tam, W.L., Tan, E.H., Creasy, C., Tan, D.S.W., Hillmer, A.M., and Zhai, W. (2020) The genomic landscape and ethnic specificity of lung Adenocarcinoma in Asia. Nature Genetics, 52(2):177-186.
4. Goh, J.Y., Feng, M., Wang, W., Oguz, G., Yatim, S.M.J.M., Lee, P.L., Bao, Y., Lim, T.H., Wang, P., Tam, W.L., Kodahl, A.R., Lyng, M.B., Sarma, S., Lin, S.Y., Lezhava, A., Yap, Y.S., Lim, A.S.T., Hoon, D.S.B., Ditzel, H.J., Lee, S.C., Tan, E.Y., Yu, Q. (2017) Chromosome 1q21.3 amplification is a trackable biomarker and actionable target for breast cancer recurrence. Nature Medicine. 23(11):1319-1330.
5. Tan, W.L., Jain, A., Takano, A., Newell, E.W., Iyer, N.G., Lim, W.T., Tan, E.H., Zhai, W., Hillmer, A.M., Tam, W.L., and Tan, D.S.W. (2016) Novel therapeutic targets on the horizon for lung cancer. Lancet Oncology. 17:e347
6. Zhang, W.C., Chin, T.M., Yang, H., Nga, M.N., Lunny, D.P., Lim, E.K.H., Sun, L.L., Pang, Y.H., Leow, Y.N., Malusay, S.R.Y., Lim, P.X.H., Lee, J.Z., Tan, B.J.W., Shyh-Chang, N, Lim, E.H., Lim, W.T., Tan, D.S.W., Tan, E.H., Tai, B.C., Soo, R.A., Tam, W.L.# and Lim, B.# (2016) Tumor-initiating cell-specific miR-1246 and miR-1290 expression converge to promote non-small cell lung cancer progression. Nature Communications. 7:11702. #Corresponding authors
7. Pattabiraman, D.R., Bierie, B., Kober, K., Krall, J., Zill, C., Reinhardt, F., Tam, W.L. and Weinberg, R.A. (2016). cAMP-induced activation of PKA leads to epigenetic reprogramming-mediated mesenchymal-to-epithelial transition and exit from the cancer stem cell state. Science. 351:6277
8. 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. 525:256-60.
9. 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.
10. 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.
11. Tam, W.L. and Ng, H.H. (2014). Sox2: Masterminding the root of cancer. Cancer Cell. 26:3-5.
12. 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.
13. Tam, W.L. and Weinberg, R.A. (2013). The epigenetics of epithelial-mesenchymal plasticity in cancer. Nature Medicine. 19:1438-1449
14. 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
15. 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. (2012). Slug and Sox9 cooperatively determine the mammary stem cell state. Cell. 148:1015-1028
16. 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
17. 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
18. 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
19. 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
20. 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