Epigenetic mechanisms play a central role in regulating cell fate determination processes during normal development and pathogenesis. Deciphering these mechanisms will shed light on developing novel therapies for treating human developmental syndromes and cancer.
Our lab is interested in understanding how epigenetic events, including histone modifications, DNA modifications, and nucleosome positioning, impact cell fate. One major focus of our lab is the roles of lysine methyltransferases (KMTs) and lysine demethylases (KDMs) in regulating stem cell self-renewal and differentiation. We also focus on the crosstalk between different epigenetic pathways in modulating transcription, higher order chromatin architecture, and animal development. Moreover, we are interested in revealing the functions of enhancers and the machineries regulating them in controlling gene expression and cell fate transition.
We are dedicated to mentoring and training the next generation of exceptional scientists in biomedical research. The ultimate goal of our research is to translate the newfound knowledge to benefit patients and improve public health.
- Zeng C, Chen J, Cooke EW, Subuddhi A, Roodman ET, Chen FX, Cao K.
"Demethylase-independent roles of LSD1 in regulating enhancers and cell fate transition."
Nat Commun. 2023; 14(1):4944.
- Cao K, Ugarenko M, Ozark PA, Wang J, Marshall SA, Rendleman EJ, Liang K, Wang L, Zou L, Smith ER, Yue F, Shilatifard A.
DOT1L-controlled cell-fate determination and transcription elongation are independent of H3K79 methylation.
Proc Natl Acad Sci U S A. 117:27365-27373 (2020)
- Cao K, Collings CK, Morgan MA, Marshall SA, Rendleman EJ, Ozark PA, Smith ER, and Shilatifard A.
"An Mll4/COMPASS-Lsd1 epigenetic axis governs enhancer function and pluripotency transition in embryonic stem cells."
Science Advances 4(1):eaap8747 (2018).
- Cao K, Collings CK, Marshall SA, Morgan MA, Rendleman EJ, Wang L, Sze CC, Sun T, Bartom ET,and Shilatifard A.
"SET1A/COMPASS and shadow enhancers in the regulation of homeotic gene expression."
Genes Dev. 31(8):787-801 (2017).
- Cao K and Shilatifard A.
"Inhibit globally, act locally: CDK7 inhibitors in cancer therapy."
Cancer Cell. 26(2):158-9 (2014).
- Cao K, Lailler N, Zhang Y, Kumar A, Uppal K, Liu Z, Lee EK, Wu H, Medrzycki M, Pan C, Ho PY, Cooper GP Jr, Dong X, Bock C, Bouhassira EE, and Fan Y.
"High-resolution mapping of h1 linker histone variants in embryonic stem cells."
PLoS Genet. 9(4):e1003417 (2013).
- Sze CC, Cao K, Collings CK, Marshall SA, Rendleman EJ, Ozark PA, Chen FX, Morgan MA, Wang L, and Shilatifard A.
"Histone H3K4 methylation-dependent and -independent functions of Set1A/COMPASS in embryonic stem cell self-renewal and differentiation."
Genes Dev. 31(17):1732-1737 (2017).
- Sze CC, Ozark PA, Cao K, Ugarenko M, Das S, Wang L, Marshall SA, Rendleman EJ, Ryan CA, Zha D, Douillet D, Chen FX, and Shilatifard A.
"Coordinated regulation of cellular identity-associated H3K4me3 breadth by the COMPASS family."
Science Advances, 6(26), eaaz4764 (2020).
- Douillet D, Sze CC, Ryan C, Piunti A, Shah AP, Ugarenko M, Marshall SA, Rendleman EJ, Zha D, Helmin KA, Zhao Z, Cao K, Morgan MA, Singer BD, Bartom ET, Smith ER, and Shilatifard A.
"Uncoupling histone H3K4 trimethylation from developmental gene expression via an equilibrium of COMPASS, Polycomb and DNA methylation."
Nature Genetics, 52(6), 615–625 (2020).
- Rickels R, Herz HM, Sze CC, Cao K, Morgan MA, Collings CK, Gause M, Takahashi YH, Wang L, Rendleman EJ, Marshall SA, Krueger A, Bartom ET, Piunti A, Smith ER, Abshiru NA, Kelleher NL, Dorsett D, and Shilatifard A.
"Histone H3K4 monomethylation catalyzed by Trr and mammalian COMPASS-like proteins at enhancers is dispensable for development and viability."
Nat Genet. 49(11):1647-1653 (2017).
- Chen FX, Xie P, Collings CK, Cao K, Aoi Y, Marshall SA, Rendleman EJ, Ugarenko M, Ozark PA, Zhang A, Shiekhattar R, Smith ER, Zhang MQ, and Shilatifard A.
"PAF1 regulation of promoter-proximal pause release via enhancer activation."
Science. 357(6357):1294-1298 (2017)
- Hu D, Gao X, Cao K, Morgan MA, Mas G, Smith ER, Volk AG, Bartom ET, Crispino JD, Di Croce L, and Shilatifard A.
"Not All H3K4 Methylations Are Created Equal: Mll2/COMPASS Dependency in Primordial Germ Cell Specification."
Mol. Cell. 65(3):460-475 (2017).