Professor, Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
Faculty, Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX
Research interests: The role of histone-modifying enzymes
Key Words: Histone modifications, Histone-modifying enzymes, Gene regulation, Epigenetics, Tumor suppression & Cancer
My laboratory is interested in understanding the role of histone modifications. Histone modifications include methylation, acetylation, phosphorylation and ubiquitylation, and play an essential role in regulating gene expression and chromatin architecture, consequently affecting numerous biological processes such as cellular differentiation, development and tumorigenesis.
It has been increasingly evident that epigenetic changes ― changes in a phenotype without altering DNA sequence ― are a common basis for cancer phenotype. While the link between epigenetic aberration and cancer development is clear, the epigenetic mechanisms underlying oncogenic processes remain to be studied. Recently, changes in histone modifications have been emerged as a key player in epigenetic alteration involved in the oncogenic events such as inactivation of tumor suppression pathways and activation of oncogenes.
Since histone modifications are controlled by a cohort of histone-modifying enzymes, we primarily explore the biochemical and biological role of histone-modifying enzymes, especially with an emphasis on histone methyltransferases and demethylases. In parallel, we also study the epigenetic role of these enzymes in the oncogenic events or tumor suppression pathways.
|2003||Johns Hopkins University, School of Medicine, Baltimore, MD, USA, PHD, Biological Chemistry, Dr. Peter L Pedersen|
|1993||Seoul National University, Seoul, KOR, MS, Agricultural Chemistry|
|1991||Seoul National University, Seoul, KOR, BS, Agricultural Chemistry|
|2004-2007||Research Fellowship, The Wistar Institute, Philadelphia, PA|
|2003-2004||Research Fellowship, Johns Hopkins University, School of Medicine, Baltimore, MD|
Faculty, Graduate School of Biomedical Sciences (GSBS), The University of Texas Health Science Center, Houston, TX, 2009 - Present
Faculty, Cancer Biology Program, Graduate School of Biomedical Science, The University of Texas Health Science Center and MD Anderson Cancer Center, Houston, TX, 2009 - Present
Faculty, Division of Basic Science Research, Center for Biological Pathways, The University of Texas MD Anderson Cancer Center, Houston, TX, 2009 - Present
- Alam H, Tang M, Maitituoheti M, Dhar SS, Kumar M, Han CY, Ambati CR, Amin SB, Gu B, Chen TY, Lin YH, Chen J, Muller FL, Putluri N, Flores ER, DeMayo FJ, Baseler L, Rai K, Lee MG. KMT2D Deficiency Impairs Super-Enhancers to Confer a Glycolytic Vulnerability in Lung Cancer. Cancer Cell 37(4):599-617, 2020. e-Pub 2020. PMID: 32243837.
- Wang G, Long J, Gao Y, Zhang W, Han F, Xu C, Sun L, Yang SC, Lan J, Hou Z, Cai Z, Jin G, Hsu CC, Wang YH, Hu J, Chen TY, Li H, Lee MG, Lin HK. SETDB1-mediated methylation of Akt promotes its K63-linked ubiquitination and activation leading to tumorigenesis. Nature Cell Biology 21(2):214-225, 2019. e-Pub 2019. PMID: 30692626.
- Park MK, Yao Y, Xia W, Setijono SR, Kim JH, Vila IK, Chiu HH, Wu Y, Billalabeitia EG, Lee MG, Kalb RG, Hung MC, Pandolfi PP, Song SJ, Song MS. PTEN self-regulates through USP11 via the PI3K-FOXO pathway to stabilize tumor suppression. Nature Communications 10(1):636, 2019. e-Pub 2019. PMID: 30733438.
- Liu Y, Qin S, Chen TY, Lei M, Dhar SS, Ho JC, Dong A, Loppnau P, Li Y, Lee MG*, Min J*. Structural insights into trans-histone regulation of H3K4 methylation by unique histone H4 binding of MLL3/4. Nature Communications (*Co-Corresponding author) 10(1):36, 2019. e-Pub 2019. PMID: 30604749.
- Alam H, Li N, Dhar SS, Wu SJ, Lv J, Chen K, Flores ER, Baseler L, Lee MG. HP1γ promotes lung adenocarcinoma by downregulating the transcription-repressive regulators NCOR2 and ZBTB7A. Cancer Research 78(14):3834-3848, 2018. e-Pub 2018. PMID: 29764865.
- Dhar SS, Zhao D, Lin T, Gu B, Pal K, Wu SJ, Alam H, Lv J, Yun K, Gopalakrishnan V, Flores ER, Northcott PA, Rajaram V, Li W, Shilatifard A, Sillitoe RV, Chen K, Lee MG. MLL4 Is Required to Maintain Broad H3K4me3 Peaks and Super-Enhancers at Tumor Suppressor Genes. Molecular Cell 70(5):825-841.e6, 2018. e-Pub 2018. PMID: 29861161.
- Chen TY, Lee SH, Dhar SS, Lee MG. Protein arginine methyltransferase 7-mediated microRNA-221 repression maintains Oct4, Nanog, and Sox2 levels in mouse embryonic stem cells. J Biol Chem 293(11):3925-3936, 2018. e-Pub 2018. PMID: 29378844.
- Taube JH, Sphyris N, Johnson KS, Reisenauer KN, Nesbit TA, Joseph R, Vijay GV, Sarkar TR, Bhangre NA, Song JJ, Chang JT, Lee MG, Soundararajan R, Mani SA. The H3K27me3-demethylase KDM6A is suppressed in breast cancer stem-like cells, and enables the resolution of bivalency during the mesenchymal-epithelial transition. Oncotarget 8(39):65548-65565, 2017. e-Pub 2017. PMID: 29029452.
- Lee SH, Chen TY, Dhar SS, Gu B, Chen K, Kim YZ, Li W, Lee MG. A feedback loop comprising PRMT7 and miR-24-2 interplays with Oct4, Nanog, Klf4 and c-Myc to regulate stemness. Nucleic Acids Research 44(22):10603-10618, 2016. e-Pub 2016. PMID: 27625395.
- Li N, Li Y, Lv J, Zheng X, Wen H, Shen H, Zhu G, Chen TY, Dhar SS, Kan PY, Wang Z, Shiekhattar R, Shi X, Lan F, Chen K, Li W, Li H, Lee MG. ZMYND8 Reads the Dual Histone Mark H3K4me1-H3K14ac to Antagonize the Expression of Metastasis-Linked Genes. Molecular Cell 63(3):470-84, 2016. e-Pub 2016.
- Dhar SS, Lee SH, Chen K, Zhu G, Oh W, Allton K, Gafni O, Kim YZ, Tomoiga AS, Barton MC, Hanna JH, Wang Z, Li W, Lee MG. An essential role for UTX in resolution and activation of bivalent promoters. Nucleic Acids Research 8(8):3659-74, 2016. e-Pub 2016.
- Li N, Dhar SS, Chen TY, Kan PY, Wei Y, Kim JH, Chan CH, Lin HK, Hung MC, Lee MG. JARID1D is a suppressor and prognostic marker of prostate cancer invasion and metastasis. Cancer Research 76(4):831-43, 2016. e-Pub 2016.
- Kim J, Sharma A, Dhar SS, Lee S, Gu B, Chan CH, Lin HK, Lee MG. UTX and MLL4 Coordinately Regulate Transcriptional Programs for Cell Proliferation and Invasiveness in Breast Cancer Cells. Cancer Research 74(6):1705-17, 2014. e-Pub 2014. PMID: 24491801.
- Dhar SS, Alam H, Li N, Wagner KW, Chung J, Ahn YW, Lee MG. Transcriptional Repression of Histone Deacetylase 3 by the Histone Demethylase KDM2A Is Coupled to Tumorigenicity of Lung Cancer Cells. J Biol Chem 289:7483-7496, 2014.
- Wagner K, Alam H, Dhar S, Giri U, Li N, Wei Y, Giri D, Cascone T, Kim JH, Ye Y, Multani A, Chan CH, Erez B, Saigal B, Chung J, Lin HK, Wu X, Hung M, Heymach J, Lee MG. KDM2A Promotes Lung Tumorigenesis by Epigenetically Enhancing ERK1/2 Signaling. J Clin Invest 123:5231-5246, 2013.
- Dhar SS, Lee SH, Kan PY, Voigt P, Ma L, Shi X, Reinberg D, Lee MG. Trans-tail regulation of MLL4-catalyzed H3K4 methylation by H4R3 symmetric dimethylation is mediated by a tandem PHD of MLL4. Genes Dev 26(24):2749-62, 2012. PMID: 23249737.
- Wen H, Li J, Song T, Lu M, Kan PY, Lee MG, Sha B, Shi X. Recognition of histone H3K4 trimethylation by the plant homeodomain of PHF2 modulates histone demethylation. J Biol Chem 285(13):9322-6, 2010. e-Pub 2010. PMID: 20129925.
- Smith ER, Lee MG, Winter B, Droz NM, Eissenberg JC, Shiekhattar R, Shilatifard A. Drosophila UTX is a histone H3 Lys27 demethylase that colocalizes with the elongating form of RNA polymerase II. Mol Cell Biol 28(3):1041-6, 2008. e-Pub 2007. PMID: 18039863.
- Ingvarsdottir K, Edwards C, Lee MG, Lee JS, Schultz DC, Shilatifard A, Shiekhattar R, Berger SL. Histone H3 K4 demethylation during activation and attenuation of GAL1 transcription in Saccharomyces cerevisiae. Mol Cell Biol 27(22):7856-64, 2007. e-Pub 2007. PMID: 17875926.
- Lee MG, Villa R, Trojer P, Norman J, Yan KP, Reinberg D, Di Croce L, Shiekhattar R. Demethylation of H3K27 Regulates Polycomb Recruitment and H2A Ubiquitination. Science 318(5849):447-50, 2007. e-Pub 2007. PMID: 17761849.
- Huang J, Sengupta R, Espejo AB, Lee MG, Dorsey JA, Richter M, Opravil S, Shiekhattar R, Bedford MT, Jenuwein T, Berger SL. p53 is regulated by the lysine demethylase LSD1. Nature 449(7158):105-8, 2007. PMID: 17805299.
- Eissenberg JC, Lee MG, Schneider J, Ilvarsonn A, Shiekhattar R, Shilatifard A. The trithorax-group gene in Drosophila little imaginal discs encodes a trimethylated histone H3 Lys4 demethylase. Nature Structural & Molecular Biology 14(4):344-6, 2007. e-Pub 2007. PMID: 17351630.
- Lee MG, Norman J, Shilatifard A, Shiekhattar R. Physical and functional association of a trimethyl H3K4 demethylase and Ring6a/MBLR, a polycomb-like protein. Cell 128(5):877-887, 2007. e-Pub 2007. PMID: 17320162.
- Nicolas E, Lee MG, Hakimi MA, Cam HP, Grewal SI, Shiekhattar R. Fission yeast homologs of human histone H3 lysine 4 demethylase regulate a common set of genes with diverse functions. J Biol Chem 281(47):35983-8, 2006. e-Pub 2006. PMID: 16990277.
- Lee MG, Wynder C, Schmidt DM, McCafferty DG, Shiekhattar R. Histone H3 lysine 4 demethylation is a target of nonselective antidepressive medications. Chem Biol 13(6):563-7, 2006. PMID: 16793513.
- Lee MG, Wynder C, Bochar DA, Hakimi MA, Cooch N, Shiekhattar R. Functional interplay between histone demethylase and deacetylase enzymes. Mol Cell Biol 26(17):6395-6402, 2006. PMID: 16914725.
- Lee MG, Wynder C, Norman J, Shiekhattar R. Isolation and characterization of histone H3 lysine 4 demethylase-containing complexes. Methods 40(4):327-30, 2006. PMID: 17101444.
- Lee MG, Wynder C, Cooch N, Shiekhattar R. An essential role for CoREST in nucleosomal histone 3 lysine 4 demethylation. Nature 437(7057):432-5, 2005. e-Pub 2005. PMID: 16079794.
- Lee MG, Pedersen PL. Glucose metabolism in cancer: importance of transcription factor-DNA interactions within a short segment of the proximal region of the type II hexokinase promoter. J Biol Chem 278(42):41047-58, 2003. e-Pub 2003. PMID: 12893819.
- Alam H, Gu B, Lee MG. Histone methylation modifiers in cellular signaling pathways. Cell Mol Life Sci 72(23):4577-92, 2015. e-Pub 2015. PMID: 26305020.
- Gu B, Lee MG. Histone H3 Lysine 4 Methyltransferases and Demethylases in Self-renewal and Differentiation of Stem Cells. Cell & Bioscience 3(1):39, 2013. PMID: 24172249.
|Title:||CCE Pilot Project Fund|
|Funding Source:||The University of Texas M. D. Anderson Cancer Center|
|Title:||Role of the Histone Demethylase UTX in Breast Cancer|
|Funding Source:||Cancer Prevention & Research Institute of Texas (CPRIT)|
|Title:||Role of the Histone Demethylase JARID1d in Epigenetic Events of Prostate Cancer|
|Title:||Innovative epigenetics therapies project|
|Funding Source:||Cancer for Epigenetics Center at University of Texas MD Anderson Cancer Center|
|Title:||Solexa Sequencing allowance|
|Funding Source:||Cancer for Epigenetics Center at University of Texas M. D. Anderson Cancer Center|
|Title:||Role of the Histone Modifier KDM2A in Lung Cancer|
|Title:||Role of the Histone Methyltransferase MLL4 in Medulloblastoma|
|Title:||Targeting p53 in cancer through manipulation of p63 and p73 (From Dr. Elsa Flores)|
|Funding Source:||Cancer Prevention & Research Institute of Texas (CPRIT)|
|Title:||Role of the Histone Modifier KDM6A in Stem Cell Differentiation|