Areas of Interest
Cell fate decisions are controlled by tissue-specific transcription factors acting in concert with epigenetic regulators such as enzymes that carry out histone post-translational modifications. Epigenetic dysregulation emerges as a key characteristic of human malignancies. The Dou lab seeks to determine the epigenetic basis of normal and aberrant embryonic and hematopoietic development. By comparing the ontogeny of gene regulatory networks in embryonic stem cells as well as leukemia stem cells, the lab aims to understand how lineage-specifying transcription factors, non-coding DNA regulatory regions and epigenetic modulating enzymes cooperate to maintain or reprogram stem cell characteristics, expand differentiation potentials, and perturb disease development. These studies promise to not only advance our understanding of the context-specific roles of epigenetic modulators in development and diseases, but also provide critical insights into designing novel target-based therapeutic strategies in cancer treatment and regenerative medicine.
Honors & Awards
2014 Dean’s award in Basic Science
2012 Leukemia & Lymphoma Society Scholar Award
2011 Stand Up to Cancer IRG Award
2010 AACR Gertrude B. Elion Cancer Research Award
2010 American Cancer Society RSG Award
2007 Biomedical Science Scholar, University of Michigan
Dou Y, Milne TA, Tackett AJ, Smith ER, Fukuda A, Wysocka J, Allis CD, Chait BT, Hess JL, Roeder RG: Physical association and coordinate function of the H3 K4 methyltransferase MLL1 and the H4 K16 acetyltransferase MOF. Cell 121(6): 873-885, 2005.
Dou Y, Milne TA, Ruthenburg AJ, Lee S, Lee JW, Verdine GL, Allis CD, Roeder RG: Regulation of MLL1 H3K4 methyltransferase activity by its core components. Nat. Struct. Mol. Biol. 13(8): 713-719, 2006.
Li X, Wu L, Corsa CA, Kunkel S, Dou Y: Two mammalian MOF complexes regulate transcription activation by distinct mechanisms. Molecular Cell, 36 (2): 290-301, 2009.
Wu L, Zee BM, Wang Y, Garcia BA, Dou Y: The RING Finger Protein MSL2 in the MOF Complex Is an E3 Ubiquitin Ligase for H2B K34 and Is Involved in Crosstalk with H3 K4 and K79 Methylation. Molecular Cell, 43(1): 132-144, 2011.
Chen Y, Wan B, Wang KC, Cao F, Yang Y, Protacio A, Dou Y, Chang HY, Lei M: Crystal structure of the N-terminal region of human Ash2L shows a winged-helix motif involved in DNA binding. EMBO Rep. 12(8): 797-803, 2011.
Chen Y, Cao F, Wan B, Dou Y, Lei M: Structure of the SPRY domain of human Ash2L and its interactions with RbBP5 and DPY30. Cell Res. 22(3): 598-602, 2012.
Huang J, Wan B, Wu L, Yang Y, Dou Y, Lei M: Structural insight into the regulation of MOF in the male-specific lethal complex and the non-specific lethal complex. Cell Res. 22(6): 1078-1081, 2012.
Li X, Li L, Pandey R, Byun JS, Gardner K, Qin Z, Dou Y: The Histone Acetyltransferase MOF Is a Key Regulator of the Embryonic Stem Cell Core Transcriptional Network. Cell Stem Cell, 11(2): 163-178, 2012.
Karatas H, Townsend EC, Cao F, Chen Y, Bernard D, Liu L, Lei M, Dou Y, Wang S: High-Affinity, Small-Molecule Peptidomimetic Inhibitors of MLL1/WDR5 Protein-Protein Interaction. J. Am. Chem. Soc., 135(2): 669-682, 2013.
Pandey R, Dou Y: H2A.Z sets the stage in ESCs. Cell Stem Cell 12(2): 143-144, 2013.
Wu L, Lee SY, Zhou B, Nguyen UT, Muir TW, Tan S, Dou Y: ASH2L regulates ubiquitylation signaling to MLL: trans-regulation of H3 K4 methylation in higher eukaryotes. Molecular Cell, 49 (6): 1108-1120, 2013.
Cao F, Townsend EC, Karatas H, Xu J, Li L, Lee S, Liu L, Chen Y, Ouillette P, Zhu J, Hess JL, Atadja P, Lei M, Qin ZS, Malek S, Wang S, Dou Y: Targeting MLL1 H3K4 methyltransferase activity in mixed-lineage leukemia. Molecular cell, 53 (2): 247-61, 2014.
Wu L, Li L, Qin Z and Dou Y: MSL2 mediated H2B K34 ubiquitylation promotes RNA Pol II processivity through regulating PAF1 and pTEFb pathways. Molecular Cell, 54 (6): 920-931, 2014
For a complete list of this person’s PubMed publications, click HERE