Visit our Lab Website @ https://www.tamlab.org/
***We are recruiting BIOINFORMATICIAN, POSTDOCS, and GRADUATE STUDENTS!***
CANCER STEM CELL PROGRAM
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.
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?
- 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., Ma, S., 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. In press Abstract
- Pattabiraman DR, Bierie B, Kober KI, Thiru P, Krall JA, Zill C, Reinhardt F, Tam WL, Weinberg RA "Activation of PKA leads to mesenchymal-to-epithelial transition and loss of tumor-initiating ability." Science 2016 Mar 4 ; 351(6277) : aad3680 Abstract
- Ye X, Tam WL, Shibue T, Kaygusu z Y, Reinhardt F, Ng Eaton E, Weinberg RA "Distinct EMT programs control normal mammary stem cells and tumour-initiating cells." Nature 2015 Sep 2 Abstract
- Lu H, Clauser KR, Tam WL, Fröse J, Ye X, Eaton EN, Reinhardt F, Donnenberg VS, Bhargava R, Carr SA, Weinberg RA "A breast cancer stem cell niche supported by juxtacrine signalling from monocytes and macrophages." Nat Cell Biol 2014 Sep 28 Abstract
- Tam WL, Ng HH "Sox2: masterminding the root of cancer." Cancer Cell 2014 Jul 14 ; 26(1) : 3-5 Abstract
- Tam WL, Weinberg RA "The epigenetics of epithelial-mesenchymal plasticity in cancer." Nat Med 2013 Nov ; 19(11) : 1438-49 Epub 2013 Nov 7 Abstract
- Tam WL, Lu H, Buikhuisen J, Soh BS, Lim E, Reinhardt F, Wu ZJ, Krall JA, Bierie B, Guo W, Chen X, Liu XS, Brown M, Lim B, Weinberg RA "Protein kinase C α is a central signaling node and therapeutic target for breast cancer stem cells." Cancer Cell 2013 Sep 9 ; 24(3) : 347-64 Abstract
- Han J, Yuan P, Yang H, Zhang J, Soh BS, Li P, Lim SL, Cao S, Tay J, Orlov YL, Lufkin T, Ng HH, Tam WL#, Lim B# "Tbx3 improves the germ-line competency of induced pluripotent stem cells." Nature 2010 Feb 25 ; 463(7284) : 1096-100 Epub 2010 Feb 7. #Corresponding authors Abstract
- Lim CY*, Tam WL*,#, Zhang J*, Ang HS, Jia H, Lipovich L, Ng HH, Wei CL, Sung WK, Robson P, Yang H, Lim B# "Sall4 regulates distinct transcription circuitries in different blastocyst-derived stem cell lineages." Cell Stem Cell 2008 Nov 6 ; 3(5) : 543-54 Epub 2008 Sep 18. *Equal contributions; #Corresponding authors Abstract
- Zhang J*, Tam WL*, Tong GQ*, Wu Q, Chan HY, Soh BS, Lou Y, Yang J, Ma Y, Chai L, Ng HH, Lufkin T, Robson P, Lim B "Sall4 modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5f1." Nat Cell Biol 2006 Oct ; 8(10) : 1114-23 Epub 2006 Sep 17. *Equal contributions Abstract