Functional Epigenomics Unit
Payel Sen, Ph.D.
Head, Functional Epigenomics Unit
Laboratory of Genetics and Genomics
The Functional Epigenomics Unit, led by Dr. Sen, focuses on understanding chromatin changes during senescence, aging and age-related diseases. We employ experimental, computational, and high-throughput technologies to discover novel epigenetic targets of aging with the goal of (1) delineating the mechanism/pathway employed by these targets to regulate aging and (2) using cellular reprogramming approaches to modulate the levels of these targets for healthspan and lifespan extension.
Senescence and aging are associated with global and local changes in the chromatin landscape. These include loss of histones, imbalances in activating and repressive histone modifications, global DNA hypomethylation but focal hypermethylation, breakdown of lamina-associated heterochromatin, etc. These changes culminate in altered gene expression manifesting in decline of cellular health and disease. We seek to understand these changes in greater detail and higher resolution in the naturally aged mouse model, ultimately narrowing down on key enzymes and transcription factors that drive aging. Our long-term goal is to modulate these factors using epigenetic drugs, CRISPR/Cas9 and other cellular reprogramming strategies to improve healthspan and lifespan.
- Epigenetics/chromatin biology
- Single-cell genomics
- Senescence and Aging
Payel Sen, Head
Na Yang, Postdoctoral Fellow
Changyou Shi, Postdoctoral Fellow
Lin Wang, Postdoctoral Fellow
Jisu Ha, Bioinformatics Specialist
Sen P, Lan Y, Li CY, Sidoli S, Donahue G, Dou Z, Frederick B, Chen Q, Luense LJ, Garcia BA, Dang W, Johnson FB, Adams PD, Schultz DC, Berger SL, Histone Acetyltransferase p300 Induces De Novo Super-Enhancers to Drive Cellular Senescence. Mol Cell. 73(4):684-698.e8 (2019). PMID: 30773298
Yang N, Sen P, The senescent cell epigenome, Aging. 10(11):3590-3609 (2018) PMID: 30391936
Dou Z, Ghosh K, Vizioli MG, Zhu J, Sen P, Wangensteen KJ, Simithy J, Lan Y, Lin Y, Zhou Z, Capell BC, Xu C, Xu M, Kieckhaefer JE, Jiang T, Shoshkes-Carmel M, Tanim KMAA, Barber GN, Seykora JT, Millar SE, Kaestner KH, Garcia BA, Adams PD, Berger SL, Cytoplasmic chromatin triggers inflammation in senescence and cancer. Nature. 550(7676):402-406 (2017). PMID: 28976970
Sen P, Luo J, Hada A, Hailu SG, Dechassa ML, Persinger J, Brahma S, Paul S, Ranish J, Bartholomew B, Loss of Snf5 Induces Formation of an Aberrant SWI/SNF Complex. Cell Rep. 18(9):2135-2147 (2017). PMID: 28249160
Sen P, Shah PP, Nativio R, Berger SL, Epigenetic Mechanisms of Longevity and Aging. Cell. 166(4):822-839 (2016). PMID: 27518561
Sen P*, Dang W*, Donahue G, Dai J, Dorsey J, Cao X, Liu W, Cao K, Perry R, Lee JY, Wasko BM, Carr DT, He C, Robison B, Wagner J, Gregory BD, Kaeberlein M, Kennedy BK, Boeke JD, Berger SL, H3K36 methylation promotes longevity by enhancing transcriptional fidelity. Genes Dev. 29(13):1362-76 (2015). PMID: 26159996. *Equal contribution.