RESEARCH
While every cell within the body shares identical genetic information, the epigenome, which contains various biochemical modifications on DNA or histones, is dynamically modulated by diverse environmental signals to regulate gene expression in different tissues and cell types. More recently, large-scale epigenetic profiling studies from various consortia, such as ENCODE (Encyclopedia of DNA elements), Roadmap Epigenomics Projects, and the Cancer Genome Atlas (TCGA) program, have identified millions of putative enhancers from > 1,000 human cell/ tissue types and begun to shed light on the altered chromatin landscape during disease progression. However, the functionality of putative enhancers is largely uncharacterized. This lack of functional annotation has hampered our ability to interpret and explore the mechanisms of putative risk variants in human disease. In addition to the host genome, trillions of bacteria live inside the gastrointestinal tract (the gut microbiota) and are the major source of diverse environmental signals. Although correlations have been made between the development of different chronic diseases and the imbalance of the gut microbiota, it is still unclear how the gut microbiota contributes to gene dysregulation and leads to the onset and progression of human diseases. We have developed several advanced functional perturbation approaches for in vitro and in vivo studies to dissect the complex interactions between the gut microbiota and the host genome. Our primary research aims to 1) discover functional enhancers under different physiological conditions, 2) understand how the environmental conditions modulate host epigenome, and 3) establish a predictive model to evaluate the effects of human genetic variants modulated by environmental signals. We are in the early stage of achieving precision medicine. Understanding the interactions between the gut microbiota and the host, metabolite regulation within the gut microbiota, and how epigenetic regulation is affected will be crucial and necessary to help achieve this goal.
We welcome talented postdoctoral fellows, computational biologists, and students to join us. For more information, please visit our lab website (https://bensonchenlab.com).
Selected Publications
- Chen PB, Black AS, Sobel AL, Zhao Y, Mukherjee P, Molparia B, Moore NE, Muench G, Wu J, Chen W, Pinto A, Maryanoff BE, Saghatelian A, Soroosh P, Torkamani A, Leman LJ, Ghadiri MR. "Directed remodeling of the mouse gut microbiome inhibits the development of atherosclerosis." Nat Biotechnol. 2020 Nov; 38(11): 1288-1297.
- Fiaux PC, Chen HV, Chen PB, Chen AR, McVicker G. "Discovering functional sequences with RELICS, an analysis method for tiling CRISPR screens." PLOS Comput Biol. 2020 Sep 16; 16 (9):e1008194.
- Chen PB, Chen HV, Acharya D, Rando OJ, Fazzio TG. "R-loops regulate promoter-proximal chromatin architecture and cellular differentiation." Nat Struct Mol Biol. 2015 Dec; 22(12):999-1007. (Cover article)
- Chen PB, Zhu LJ, Hainer SJ, McCannell KN, Fazzio TG. "Unbiased chromatin accessibility profiling by RED-seq uncovers unique features of nucleosome variants in vivo." BMC Genomics. 2014 Dec 15; 15:1104.
- Chen PB, Hung JH, Hickman TL, Coles AH, Carey JF, Weng Z, Chu F, Fazzio TG. "Hdac6 regulates Tip60-p400 function in stem cells." Elife. 2013 Dec 3;2:e01557.
- Yildirim O, Li R, Hung JH, Chen PB, Dong X, Ee LS, Weng Z, Rando OJ, Fazzio TG. "Mbd3/NURD complex regulates expression of 5-hydroxymethylcytosine marked genes in embryonic stem cells." Cell. 2011 Dec 23;147(7):1498-510.
- Hua KT, Tan CT, Johansson G, Lee JM, Yang PW, Lu HY, Chen CK, Su JL, Chen PB, Wu YL, Chi CC, Kao HJ, Shih HJ, Chen MW, Chien MH, Chen PS, Lee WJ, Cheng TY, Rosenberger G, Chai CY, Yang CJ, Huang MS, Lai TC, Chou TY, Hsiao M, Kuo ML. "N--acetyltransferase 10 protein suppresses cancer cell metastasis by binding PIX protein and inhibiting Cdc42/Rac1 activity." Cancer Cell. 2011 Feb 15;19(2):218-31.
- Su JL*, Chen PB*, Chen YH, Chen SC, Chang YW, Jan YH, Cheng X, Hsiao M, Hung MC. "Downregulation of microRNA miR-520h by E1A contributes to anticancer activity." Cancer Res. 2010 Jun 15;70(12):5096-108.