Education & Training
- B.S., Biochemistry, Sichuan University, Chengdu P.R. China- 1990
- Ph.D., Molecular Biology, University of Southern California- 1995
- Postdoc Fellow, Johns Hopkins University School of Medicine- 1995-1999
Research Interest Summary
The immediate goal of our research is to understand how anticancer drugs kill cancer cells, and more importantly, why they fail so often. Our research has focused on proteins that control discrete steps of programmed cell death, including PUMA, Bax, BID, SMAC, and Mcl-1, which are directly or indirectly regulated by the most frequently mutated or altered tumor suppressors and oncogenes such as p53, APC, c-Myc and KRAS. Through analyses of these cell death regulators and their associated protein networks under the influence of oncogenic mutations and other alterations, we try to gain deep understanding on how cell death is initiated and executed in colon cancer cells, why some colon cancer cells are not sensitive to anticancer drugs, and what can be done to restore their sensitivity. Our long-term goal is to develop novel strategies and agents to improve colon cancer therapy and prevention.
The specific projects in our lab are focused on four areas: (1) understand how cell death regulators modulate therapeutic response; (2) determine how anticancer drugs kill colon cancer cells; (3) delineate the role of cancer stem cell in cancer prevention; and (4) identify novel small molecules to target cell death regulators to improve colon cancer therapy and prevention.
Tan, X., Tong, J., Wang, Y.J., Fletcher, R., Schoen, R.E., Yu, J., Shen, L.*, and Zhang, L.* (2019) BET inhibitors potentiate chemotherapy and killing of SPOP-mutant colon cancer cells via induction of DR5. Cancer Research 79: 1191-1203.
Chen, D., Ni, H.M., Wang, L., Ma, X., Yu, J., Ding, W.X.* and Zhang, L.* (2019) PUMA induction mediates acetaminophen-induced necrosis and liver injury. Hepatology 2018 Dec 14. doi: 10.1002/hep.30422. [Epub ahead of print]. PMID: 29895675.
Tong, J., Zheng, X., Tan, X., Fletcher, R., Nikolovska-Coleska, Z., Yu, J. and Zhang, L. (2018) Mcl-1 phosphorylation without degradation mediates sensitivity to HDAC inhibitors by liberating BH3-only proteins. Cancer Research 78: 4704-4715.
Chen, D., Tong, J., Yang, L., Wei, L., Stolz, D.B., Yu, J., Zhang, J. and Zhang, L. (2018) PUMA amplifies necroptosis signaling by activating cytosolic DNA sensors. Proc. Natl. Acad. Sci. USA. 115: 3930-3935.
Leibowitz, B.J., Yang, L., Wei, L., Buchanan, M.E., Rachid, M., Parise, R.A., Beumer, J.H., Eiseman, J.L., Schoen, R.E., Zhang, L. and Yu, J. Targeting p53-dependent stem cell loss for intestinal chemoprotection (2018) Science Translational Medicine 2018 Feb 7;10(427). pii: eaam7610. doi: 10.1126/scitranslmed.aam 7610.
Tong, J., Wang, P., Tan, S., Chen, D., Nikolovska-Coleska, Z., Zou, F., Yu, J. and Zhang, L. (2017) Mcl-1 degradation is required for targeted therapeutics to eradicate colon cancer cells. Cancer Research 77: 2512-2521.
Leibowitz, B., Qiu, W., Buchanan, M.E., Zou, F., Vernon, P.V., Moyer, M.P., Yin, X.M., Schoen, R.E., Yu, J., and Zhang, L. (2014) BID mediates selective killing of APC-deficient cells in intestinal tumor suppression by non-steroidal anti-inflammatory drugs. Proc. Natl. Acad. Sci. USA. 111:16520-16525. PMCID: PMC4246283.
Qiu, W., Wang, X., Leibowitz, B., Liu, H., Barker, N., Okada, H., Oue, N., Yasui W., Clevers, H., Schoen, R., Yu, J. and Zhang, L. (2010) Chemoprevention by nonsteroidal anti-inflammatory drugs eliminates oncogenic intestinal stem cells via SMAC-dependent apoptosis. Proc. Natl. Acad. Sci. USA. 107: 20027-20032. PMCID: PMC2993406.
Zhang, L., Yu, J., Park, B.H., Kinzler, K.W. and Vogelstein, B. (2000) Role of BAX in the apoptotic response to anti-cancer agents. Science 290: 989-992.
Zhang, L. *, Zhou, W. *, Velculescu, V.E., Kern, S.E., Hruban, R.H., Hamilton, S.R., Vogelstein, B. and Kinzler, K.W. (1997) Gene expression profiles in normal and cancer cells. Science 276: 1268-1272.