The research activities in our laboratory are focused on signaling pathway identification and molecular targeting of pediatric cancers. These include studying the roles of MDM2 overexpression, MYCN amplification and dysregulation of the inhibitor of apoptosis protein (IAP) family in oncogenesis and progression of disease, as well as in the development of drug resistance. Our current research programs build logically on our previous work, translating basic studies on MDM2, IAP and MYCN-mediated signaling into first preclinical and later a clinical investigation of small molecule inhibitors targeting MDM2, IAP and MYCN for use as novel cancer treatments.
The research projects in our lab include: (1) The interaction between MDM2 protein and XIAP mRNA in cancer progression and drug resistance; (2) Dual inhibition of MDM2 and XIAP by selected small molecule compounds as novel therapeutic strategy in pediatric cancer; (3) Targeting MYCN mRNA by selected small molecule inhibitors in MYCN-amplified neuroblastoma.
Tao Liu, PhD
Education: 2004, PhD, Tongji Medical College, Huazhong University of Science & Technology, China
Wu Z, Gu L, Zhang S, Liu T, Lukka PB, Meibohm B, Bollinger JC, Zhou M, Li W. Discovery of N-(3,4-Dimethylphenyl)-4-(4-isobutyrylphenyl)-2,3,3a,4,5,9b-hexahydrofuro[3,2-c]quinoline-8-sulfonamide as a Potent Dual MDM2/XIAP Inhibitor. J Med Chem. 2021 Feb 25;64(4):1930-1950. doi: 10.1021/acs.jmedchem.0c00932. Epub 2021 Feb 8. PMID: 33556244.
Liu T, Zhang H, Yi S, Gu L, Zhou M. Mutual regulation of MDM4 and TOP2A in cancer progression. Mol Oncol. 2019;13:1047-1058.
Gu L, Zhang H, Liu T, Draganov A, Yi S, Wang B, Zhou M. Inhibition of MDM2 by a rhein-derived compound AQ-101 supresses cancer development in SCID mice. Mol Cancer Ther. 2018;17:497-507.
Liu T, Xiong J, Yi S, Zhang H, Zhou S, Gu L, Zhou M. FKBP12 enhances sensitivity to chemotherapy-induced cancer cell apoptosis by inhibiting MDM2. Oncogene 2017,36(12):1678-1686.
Dong L, Yu WM, Zheng H, Loh ML, Bunting ST, Pauly M, Huang G, Zhou M, Broxmeyer HE, Scadden DT, Qu CK. Leukaemogenic effects of Ptpn11 activating mutations in the stem cell microenvironment. Nature 2016, 539(7628):304-308.
Gu L, Zhang H, Liu T, Zhou S, Du Y, Xiong J, Yi S, Qu CK, Fu H and Zhou M. Discovery of dual inhibitors of MDM2 and XIAP for cancer treatment. Cancer Cell 2016, 30:623-636.
Liu T, Zhang H, Xiong J, Yi S, Gu L and Zhou M. Inhibition of MDM2 hompdimerization by XIAP IRES stabilizes MDM2, influencing cancer cell survival. Mol Cancer 2015 Mar 26;14:65. doi: 10.1186/s12943-015-0334-0.
Zhang H, Liu T, Yi S, Gu L and Zhou M. Targeting MYCN IRES in MYCN-amplified neuroblastoma with miR-375 inhibits tumor growth and sensitizes tumor cells to radiation. Mol Oncol. 2015;9(7):1301-11.
Zhang H, Gu L, Liu T, Chiang KY, Zhou M: Inhibition of MDM2 by nilotinib contributes to cytotoxicity in both Philadelphia-positive and negative acute lymphoblastic leukemia. PloS one 2014, 9(6):e100960.
Li J, Gu L, Zhang H, Liu T, Tian D, Zhou M, Zhou S. Berberine represses DAXX gene transcription and induces cancer cell apoptosis. Lab Invest. 2013;93:354-64.
Huang M, Zhang H, Liu T, Tian D, Gu L, Zhou M. Triptolide inhibits MDM2 and induces apoptosis in acute lymphoblastic leukemia cells through a p53-independent pathway. Mol Cancer Ther. 2013;12:184-94.
Zhang H, He J, Li J, Tian D, Gu L, Zhou M. Methylation of RASSF1A gene promoter is regulated by p53 and DAXX. FASEB J. 2013;27:232-42.
Gu L, Zhang H, He J, Li J and Zhou M. MDM2 regulates MYCN mRNA stabilization and translation in human neuroblastoma cells. Oncogene 2012;31:1342-53.
He J, Gu L and Zhou M. Cross-talk between MYCN and MDM2-p53 signal pathways regulates tumor cell growth and apoptosis in neuroblastoma. Cell Cycle 2011;10:2994-3002.
Zhou S, Gu L, He J, Zhang H, Zhou M. MDM2 Regulates Vascular Endothelial Growth Factor mRNA Stabilization in Hypoxia. Mol Cell Biol. 2011;31:4928-37.
Zhang X, Gu L, Li J, Shah N, He J, Yang L, Hu Q, Zhou M. Degradation of MDM2 by the interaction between berberine and DAXX leads to potent apoptosis in MDM2-overexpressing cancer cells. Cancer Res. 2010;70:9895-9904.
Yang L, Gu L, Li Z and Zhou M. Translation of TRAF1 is regulated by IRES-dependent mechanism and stimulated by vincristine. Nucleic Acids Res. 2010;38:4503-4513.
Ling X, Calinski D, Chana-Khan AA, Zhou M, Li F. Cancer cell sensitivity to bortezamib is associated with survivin expression and p53 status but not cancer cell types. J Exp Clin Cancer Res 2010;29:8-
Gu L, Zhu N, Zhang H, Durden DL, Feng Y and Zhou M. Regulation of XIAP translation and induction by MDM2 following irradiation. Cancer Cell, 2009;15:363-375.