Biography

2022.7- PI

Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, Hubei, China

2009.3- Professor

College of Life Sciences, Wuhan University, Wuhan, Hubei, China

2007-2009 Post Dr. Research Asso.

Shilatifard Lab, Stowers Institute for Medical Research, Kansas City, MO, USA

2004-2007 Post Dr. Asso.

Department of Genetics, School of Medicine, Yale University, New Haven, Connecticut, USA

1999-2004 Ph. D

Department of Cell Biology and Genetics, College of Life Sciences, Peking University, Beijing, PR. China

2001-2002 Visiting Student

Department of Immunology, National Jewish Medical and Research Center, Denver, Colorado, USA

1995-1999 B.S.

Department of Cell Biology and Genetics, College of Life Sciences, Peking University, Beijing, P.R. China

Research

Our studies mainly focus on the epigenetic regulation of human diseases, such as cancer and inflammation related diseases. Cancer and inflammation are tightly related and long-tern unresolved inflammation is one of important risk factors for tumorigenesis, such as colitis-associated cancer. However, the underlying molecular mechanisms remain elusive. We are trying to understand the epigenetic regulations during inflammation-cancer transition. The main questions in our lab are: (1) How does the epigenome change in the cell during inflammation-cancer transition? (2) What are the key factors regulating inflammation and tumorigenesis? (3) What are the molecular mechanisms regulating the innate immunity pathways activated by chromatin dysregulation?

Representative  Publications

(1) Lin, X., Chen, J.D., Wang, C.Y., Cai, Z., Zhan, R., Yang, C., Zhang, L.Y., Li, L.Y., Xiao, Y.^*, Chen, M.K.^*, Wu, M.^* Cooperation of MLL1 and Jun in controlling H3K4me3 on enhancers. Genome Biology, accepted

(2) Zhang, L.Y., Wang, C.Y., Xu, Q., Mu, Z.Q., Lin, X., Li, L.Y., Xiao, Y.^*, Wu, M.^*, and Chen, M.K.^*, Removal of epigenetic repressive mark on inflammatory genes in fat liver. J Gastroenterol Hepatol, 2023.

(3) Xiao, Q., Wang, C.Y., Gao, C., Chen, J.D., Chen, J.J., Wang, Z., Ju, L.G., Tang, S.B., Yao, J., Li, F., Li, L.Y., and Wu, M.^*, Regulation of KDM5C stability and enhancer reprogramming in breast cancer. Cell Death Dis, 2022. 13(10): p. 843.

(4) Xiao, Q., Xiao, Y., Li, L.Y., Chen, M.K.^*, and Wu, M.^*, Multifaceted regulation of enhancers in cancer. Biochim Biophys Acta Gene Regul Mech, 2022. 1865(6): p. 194839.

(5) Chen, L., Yang, C., Tang, S.-B., Long, Q.-Y., Chen, J.-D., Wu, M.^*, and Li, L.-Y.^*, Inhibition of histone methyltransferase SETD8 represses DNA virus replication. Cell Insight, 2022. 1(3).

(6) Chen, L., Luo, Z., Zhao, C., Li, Q., Geng, Y., Xiao, Y., Chen, M.K., Li, L., Chen, Z.X.^*, and Wu, M.^*, Dynamic Chromatin States Coupling with Key Transcription Factors in Colitis-Associated Colorectal Cancer. Adv Sci (Weinh), 2022: p. e2200536.

(7) Li, Q.L., Lin, X., Yu, Y.L., Chen, L., Hu, Q.X., Chen, M., Cao, N., Zhao, C., Wang, C.Y., Huang, C.W., Li, L.Y., Ye, M. ^*, and Wu, M. ^*, Genome-wide profiling in colorectal cancer identifies PHF19 and TBC1D16 as oncogenic super enhancers. Nat Commun, 2021. 12(1): p. 6407.

(8) Hu, Q.X., Wang, H.Y., Jiang, L., Wang, C.Y., Ju, L.G., Zhu, Y., Zhong, B., Wu, M. ^*, Wang, Z. ^*, and Li, L.Y. ^*, Histone demethylase LSD1 promotes RIG-I poly-ubiquitination and anti-viral gene expression. PLoS Pathog, 2021. 17(9): p. e1009918.

(9) Wang, Z., Chen, J., Gao, C., Xiao, Q., Wang, X.W., Tang, S.B., Li, Q.L., Zhong, B., Song, Z.Y., Shu, H.B., Li, L.Y., and Wu, M. ^*, Epigenetic Dysregulation Induces Translocation of Histone H3 into Cytoplasm. Adv Sci (Weinh), 2021: p. e2100779.

(10) Wang, C.Y., Yu, G.T., Gao, C., Chen, J., Li, Q.L., Zhang, L., Wu, M. ^*, Sun, Z.J. ^*, and Li, L.Y. ^*, Genome-Wide Enhancer Analysis Reveals the Role of AP-1 Transcription Factor in Head and Neck Squamous Cell Carcinoma. Front Mol Biosci, 2021. 8: p. 701531.

(11) Zheng, J.Y., Wang, C.Y., Gao, C., Xiao, Q., Huang, C.W., Wu, M. ^*, and Li, L.Y. ^*, MLL3 suppresses tumorigenesis through regulating TNS3 enhancer activity. Cell Death Dis, 2021. 12(4): p. 364.

(12) Xu, L., Zheng, Y., Li, X., Wang, A., Huo, D., Li, Q., Wang, S., Luo, Z., Liu, Y., Xu, F., Wu, X., Wu, M. ^*, and Zhou, Y. ^*, Abnormal neocortex arealization and Sotos-like syndrome-associated behavior in Setd2 mutant mice. Sci Adv, 2021. 7(1).

(13) Li, X.J., Li, Q.L., Ju, L.G., Zhao, C., Zhao, L.S., Du, J.W., Wang, Y., Zheng, L., Song, B.L., Li, L.Y., Li, L. ^*, and Wu, M. ^*, Deficiency of Histone Methyltransferase SET Domain-Containing 2 in Liver Leads to Abnormal Lipid Metabolism and HCC. Hepatology, 2021. 73(5): p. 1797-1815.

(14) Yao J., Lei P.J., Li Q.L., Chen J., Tang S.B., Xiao Q., Lin X., Wang X., Li L.Y., Wu M.^* GLIS2 promotes colorectal cancer through repressing enhancer activation. Oncogenesis 2020, 9:57.

(15) Gao C., Chen L., Tang S.B., Long Q.Y., He J.L., Zhang N.A., Shu H.B., Chen Z.X., Wu M.^*, Li L.Y.^* The epigenetic landscapes of histone modifications on HSV-1 genome in human THP-1 cells. Antiviral Res 2020, 176:104730.

(16) Wang H.Y., Long Q.Y., Tang S.B., Xiao Q., Gao C., Zhao Q.Y., Li Q.L., Ye M., Zhang L., Li L.Y., Wu M.* Histone demethylase KDM3A is required for enhancer activation of hippo target genes in colorectal cancer. Nucleic Acids Res 2019, 47:2349-2364.

(17) Li Q.L., Wang D.Y., Ju L.G., Yao J., Gao C., Lei P.J., Li L.Y., Zhao X.L.^*, Wu M.^* The hyper-activation of transcriptional enhancers in breast cancer. Clin Epigenetics 2019, 11:48.

(18) Ju L.G., Zhu Y., Long Q.Y., Li X.J., Lin X., Tang S.B., Yin L., Xiao Y., Wang X.H., Li L., Zhang L., Wu M.^* SPOP suppresses prostate cancer through regulation of CYCLIN E1 stability. Cell Death Differ 2019, 26:1156-1168.

(19) Zhu K., Lei P.J., Ju L.G., Wang X., Huang K., Yang B., Shao C., Zhu Y., Wei G., Fu X.D., Li L., Wu M.^* SPOP-containing complex regulates SETD2 stability and H3K36me3-coupled alternative splicing. Nucleic Acids Res 2017, 45:92-105.

(20) Wang Z., Long Q.Y., Chen L., Fan J.D., Wang Z.N., Li L.Y.^*, Wu M.^*, Chen X.^* Inhibition of H3K4 demethylation induces autophagy in cancer cell lines. Biochim Biophys Acta 2017, 1864:2428-2437.

(21) Li Q.L., Lei P.J., Zhao Q.Y., Li L., Wei G.^*, Wu M.^* Epigenomic analysis in a cell-based model reveals the roles of H3K9me3 in breast cancer transformation. Epigenomics 2017, 9:1077-1092.

(22) Ju L.G., Zhu Y., Lei P.J., Yan D., Zhu K., Wang X., Li Q.L., Li X.J., Chen J.W., Li L.Y.^*, Wu M.^* TTLL12 Inhibits the Activation of Cellular Antiviral Signaling through Interaction with VISA/MAVS. J Immunol 2017, 198:1274-1284.

(23) Jia X., Long Q., Miron R.J., Yin C., Wei Y., Zhang Y.^*, Wu M.^* Setd2 is associated with strontium-induced bone regeneration. Acta Biomater 2017, 53:495-505.

(24) Zhao Q.Y., Lei P.J., Zhang X., Zheng J.Y., Wang H.Y., Zhao J., Li Y.M., Ye M., Li L., Wei G.^*, Wu M.* Global histone modification profiling reveals the epigenomic dynamics during malignant transformation in a four-stage breast cancer model. Clin Epigenetics 2016, 8:34.

(25) Su S.K., Li C.Y., Lei P.J., Wang X., Zhao Q.Y., Cai Y., Wang Z., Li L.^*, Wu M.^* The EZH1-SUZ12 complex positively regulates the transcription of NF-kappaB target genes through interaction with UXT. J Cell Sci 2016, 129:2343-2353.

(26) Zhu K., Wang X., Ju L.G., Zhu Y., Yao J., Wang Y., Wu M.^*, Li L.Y.^* WDR82 Negatively Regulates Cellular Antiviral Response by Mediating TRAF3 Polyubiquitination in Multiple Cell Lines. J Immunol 2015, 195:5358-5366.

(27) Fan J.D., Lei P.J., Zheng J.Y., Wang X., Li S., Liu H., He Y.L., Wang Z.N., Wei G., Zhang X., Li L.Y.^*, Wu M.^* The selective activation of p53 target genes regulated by SMYD2 in BIX-01294 induced autophagy-related cell death. PLoS One 2015, 10:e0116782.

(28) Wang X., Ju L., Fan J., Zhu Y., Liu X., Zhu K., Wu M.^*, Li L.^* Histone H3K4 methyltransferase Mll1 regulates protein glycosylation and tunicamycin-induced apoptosis through transcriptional regulation. Biochim Biophys Acta 2014, 1843:2592-2602.

(29) Zhao Q., Fan J., Hong W., Li L., Wu M.^* Inhibition of cancer cell proliferation by 5-fluoro-2'-deoxycytidine, a DNA methylation inhibitor, through activation of DNA damage response pathway. Springerplus 2012, 1:65.

(30) Wang X., Zhu K., Li S., Liao Y., Du R., Zhang X., Shu H.B., Guo A.Y., Li L.^*, Wu M.^* MLL1, a H3K4 methyltransferase, regulates the TNFalpha-stimulated activation of genes downstream of NF-kappaB. J Cell Sci 2012, 125:4058-4066.

(31) Wu M.^*, Shu H.B.^* MLL1/WDR5 complex in leukemogenesis and epigenetic regulation. Chin J Cancer 2011, 30:240-246.

(32) Wu M. ^#, Wang P.F.^#, Lee J.S., Martin-Brown S., Florens L., Washburn M., Shilatifard A. Molecular regulation of H3K4 trimethylation by Wdr82, a component of human Set1/COMPASS. Mol Cell Biol 2008, 28:7337-7344.

(33) Higa L.A. ^#, Wu M. ^#, Ye T., Kobayashi R., Sun H., Zhang H. CUL4-DDB1 ubiquitin ligase interacts with multiple WD40-repeat proteins and regulates histone methylation. Nat Cell Biol 2006, 8:1277-1283.

(34) Banks D. ^#, Wu M. ^#, Higa L.A., Gavrilova N., Quan J., Ye T., Kobayashi R., Sun H., Zhang H. L2DTL/CDT2 and PCNA interact with p53 and regulate p53 polyubiquitination and protein stability through MDM2 and CUL4A/DDB1 complexes. Cell Cycle 2006, 5:1719-1729.

(35) Wu M. ^#, Xu L.G., Su T., Tian Y., Zhai Z., Shu H.B. AMID is a p53-inducible gene downregulated in tumors. Oncogene 2004, 23:6815-6819.

(36) Wu M. ^#, Xu L.G., Zhai Z., Shu H.B. SINK is a p65-interacting negative regulator of NF-kappaB-dependent transcription. J Biol Chem 2003, 278:27072-27079.

(37) Xu L.G. ^#, Wu M. ^#, Hu J., Zhai Z., Shu H.B. Identification of downstream genes up-regulated by the tumor necrosis factor family member TALL-1. J Leukoc Biol 2002, 72:410-416.

(38) Wu M.^#, Xu L.G.^#, Li X., Zhai Z., Shu H.B. AMID, an apoptosis-inducing factor-homologous mitochondrion-associated protein, induces caspase-independent apoptosis. J Biol Chem 2002, 277:25617-25623.

(39) Wu M. ^#, Zhao Y. and Zhai Z. The ultrastructural observation of apoptotic mouse liver cell nuclei. Journal of Chinese Electron Microscopy Society 2001, Vol. 20, No.1, 21-26.