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
Basic Science Research Award, University of Michigan Medical School, 2014
Scholar Award, Leukemia & Lymphoma Society, 2012
Innovative Research Grant, Stand Up To Cancer, 2011
Gertrude B. Elion Cancer Research Award, American Association for Cancer Research, 2010
Research Scholar Grant, American Cancer Society, 2010
Biological Sciences Scholar, University of Michigan, 2006
Epigenetic driver mutations in ARID1A shape cancer immune phenotype and immunotherapy.
Li J, Wang W, Zhang Y, Cieślik M, Guo J, Tan M, Green MD, Wang W, Lin H, Li W, Wei S, Zhou J, Li G, Jing X, Vatan L, Zhao L, Bitler B, Zhang R, Cho KR, Dou Y, Kryczek I, Chan TA, Huntsman D, Chinnaiyan AM, Zou W.
J Clin Invest. 2020, in press.
Identification of DOT1L inhibitors by structure-based virtual screening adapted from a nucleoside-focused library.
Gibbons GS, Chakraborty A, Grigsby SM, Umeano AC, Liao C, Moukha-Chafiq O, Pathak V, Mathew B, Lee YT, Dou Y, Schürer SC, Reynolds RC, Snowden TS, Nikolovska-Coleska Z.
Eur J Med Chem. 2020; 189: 112023.
p53 Integrates Temporal WDR5 Inputs during Neuroectoderm and Mesoderm Differentiation of Mouse Embryonic Stem Cells.
Li Q, Mao F, Zhou B, Huang Y, Zou Z, denDekker AD, Xu J, Hou S, Liu J, Dou Y, Rao RC.
Cell Rep. 2020; 30: 465-80.e6.
Menin inhibitor MI-3454 induces remission in MLL1-rearranged and NPM1-mutated models of leukemia.
Klossowski S, Miao H, Kempinska K, Wu T, Purohit T, Kim E, Linhares BM, Chen D, Jih G, Perkey E, Huang H, He M, Wen B, Wang Y, Yu K, Lee SC, Danet-Desnoyers G, Trotman W, Kandarpa M, Cotton A, Abdel-Wahab O, Lei H, Dou Y, Guzman M, Peterson L, Gruber T, Choi S, Sun D, Ren P, Li LS, Liu Y, Burrows F, Maillard I, Cierpicki T, Grembecka J.
J Clin Invest. 2020; 130: 981-97.
Cryo-EM structure of the human MLL1 core complex bound to the nucleosome.
Park SH, Ayoub A, Lee YT, Xu J, Kim H, Zheng W, Zhang B, Sha L, An S, Zhang Y, Cianfrocco MA, Su M, Dou Y, Cho US.
Nat Commun. 2019; 10: 5540.
Developmental ROS individualizes organismal stress resistance and lifespan.
Bazopoulou D, Knoefler D, Zheng Y, Ulrich K, Oleson BJ, Xie L, Kim M, Kaufmann A, Lee YT, Dou Y, Chen Y, Quan S, Jakob U.
Nature. 2019; 576: 301-5.
MLL1 Inhibition and Vitamin D Signaling Cooperate to Facilitate the Expanded Pluripotency State.
Zhang H, Khoa LTP, Mao F, Xu H, Zhou B, Han Y, O'Leary M, Nusrat A, Wang L, Saunders TL, Dou Y.
Cell Rep. 2019; 29: 2659-71.
For a list of publications from Michigan Research Experts, click HERE