I. Warm up cold tumors
Prostate cancer is the “cold” cancer that poory responds to immunotherapy and the tumor microenvironment is immunosuppressive.
We aim to look for the therapeutic strategies that turn the immunosuppressive microenvironment into the immunosupportive microenvironment, leading to a good response to immunotherapy.
II. Block brain metastasis
The majority of brain metastases occur in lung cancer, breast cancer, melanoma and colorectal cancer. We’re interested in understand the molecular mechanisms of brain metastases relative to primary tumour, and tumor microenviromental regulation mechanisms involved in metabolism and neuroinflammation.
III. Drug undrugable targets
Using multiple 2D/3D cancer cell culture system and animal models of various cancer types, We collaborate with Lei lab to optimize PROTAC system and apply it on undruggable targets of refractory cancers.
Investigator,Center for Life Science, Peking University
Professor & Dean,School of Life Sciences, Peking University
Co-Director,Medicine and Stem Cell Research, UCLA
Co-Director,Eli and Edythe Broad Center of Regenerative
Co-Director,Cancer Stem Cell Program
Co-Director,Institute for Molecular Medicine, UCLA
A major research focus of Dr. Wu’s laboratory is to study the molecular mechanism of PTEN tumor suppressor controlled tumorigenesis. By generating tissue-specific PTEN deficient animal models, Dr. Wu’s laboratory elucidated the important role of PTEN in regulating stem cell self-renewal, proliferation, and survival, as well as its roles in controlling the PI3K pathway. These models have been used for preclinical studies of new therapeutic agents and for identifying biomarkers for human prostate cancers.
Various genetically engineered models generated by the Wu lab and shared with the scientific communities have offered unique tools for exploring the molecular mechanisms underlying human cancers, metabolic diseases, and the development of new therapies (Cancer Cell 2003 4:209-221; PNAS 2004 101: 2082-2087; Mol. Cell Biol. 2005 25:2498-510; 2006 26:2772-81; Cancer Res. 2006 66: 6492-6496; Cancer Res. 2007 67: 6083-91). Results derived from their studies have provided novel mechanisms by which the loss of PTEN can control the functions of NKX3.1 and p53 tumor suppressors (Cancer Cell 2003 3:117-129; Cancer Cell 2006 9: 367-78). Professor Wu’s recent works are cantered on the cross-talk between the PTEN controlled PI3K pathway and other signal pathways in cancer progression and therapeutic resistance (PNAS 2009 106: 19479-84; Cancer Res. 2010 70:7114-24; Cancer Cell 2011 19, 792-804; Cancer Res 2012 72:1878-89; Cancer Res 2015 75:2749-59; Oncogene 2016 35: 3781-95; Ann oncol 2017).
Wu,H., Klingmüller, U., Besmer, P. and Lodish, H. (1995). Interaction of the erythropoietin and stem cell factor receptors. Nature 377, 242-246. PMID:7545788
Wu, H., Liu, X., Jaenisch, R. and Lodish, H. (1995). Generation of committed erythroid BFU-E and CFU-E progenitors does not require erythropoietin or the erythropoietin receptor. Cell 83, 59-67. PMID:7553874
Groszer, M., Erickson, R., Scripture-Adams, D., Lesche, R., Trumpp, A., Zack, J., Kornblum, H., Liu, X., and Wu, H. (2001) Negative Regulation of Neural Stem/Progenitor Cell Proliferation by the Pten Tumor Suppressor Gene In Vivo. Science 294: 2186-2189. PMID:11691952
Wang, S., Gao, J., Lei, Q-Y., Rozengurt, N., Pritchard, C., Jiao, J., Thomas, G., Li, G., Roy-Burman, P., Nelson, P., Liu, X., and Wu, H. (2003) Prostate-specific deletion of the murine Pten tumor suppressor gene leads to metastatic prostate cancer. Cancer Cell 4:209-221. PMID: 14522255
Guo, W., Lasky, J, Chang, C., Mosessian, S., Lewis, X., Xiao, Y., Yeh, J., Chen, J., Iruela-Arispe, L., Varella-Garcia, M. and Wu, H. (2008) Multi-genetic events collaboratively to Pten-null leukaemia stem-cell formation. Nature 453: 529-533. PMCID: PMC2840044
Mulholland, D., Tran, M.L., Cai, H., Morim, A., Wang, S., Plaisier, S., Huang, J., Garraway, I., Graeber, T. and Wu, H. (2011) Cell autonomous role of PTEN in regulating castration-resistant prostate cancer growth. Cancer Cell 19, 792-804. PMCID: PMC3157296
Cheng, J., Huang, Y., Zhang, X., Yu, Y., Wu, S., Jiao, J., Tran, L., Zhang, W., Liu, R., Zhang, L., Wang, M., Wang, M., Yan, W., Wu, Y., Chi, F., Jiang, P., Zhang, X., Wu, H. (2020) TRIM21 and PHLDA3 negatively regulate the crosstalk between the PI3K/AKT pathway and PPP metabolism. Nat Commun 11(1):1880. PMCID: PMC7170963