The Berger Lab seeks to understand how epigenetic mechanisms and chromatin alterations with aging and cellular senescence contribute to gene expression and age-associated diseases, including cancer and neurodegeneration. Our studies have demonstrated unequivocally that dramatic changes in the chromatin landscape occur in both model organisms with aging and in human cells with senescence. Our current work combines cell biology and the powerful genome-wide approaches, and investigates diverse model systems ranging from yeast, worms, and cultured cells to mouse models and human patient samples. Importantly, as epigenetic changes are considered to be largely reversible, unlike permanent genetic mutations in DNA, an understanding of these processes holds significant promise to provide opportunities for therapeutic intervention and disease modulation.

Research Paper Link


SIRT1 is downregulated by autophagy in senescence and ageing
Xu C, Wang L, Fozouni P, Evjen G, Chandra V, Jiang J, Lu C, Nicastri M, Bretz C, Winkler JD, Amaravadi R, Garcia BA, Adams PD, Ott M, Tong W, Johansen T, Dou Z, Berger SL. Nat Cell Biol. 2020 Oct;22(10):1170-1179. doi: 10.1038/s41556-020-00579-5. Epub 2020 Sep 28.PMID: 32989246

Mitochondria-to-nucleus retrograde signaling drives formation of cytoplasmic chromatin and inflammation in senescence
Vizioli MG, Liu T, Miller KN, Robertson NA, Gilroy K, Lagnado AB, Perez-Garcia A, Kiourtis C, Dasgupta N, Lei X, Kruger PJ, Nixon C, Clark W, Jurk D, Bird TG, Passos JF, Berger SL, Dou Z, Adams PD. Genes Dev. 2020 Mar 1;34(5-6):428-445. doi: 10.1101/gad.331272.119. Epub 2020 Jan 30. PMID: 32001510

Histone acetyltransferase p300 induces de novo super-enhancers to drive cellular senescence.
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. (2019) Molecular Cell 73,684-698

Senescence elicits stemness: a surprising mechanism for cancer relapse
Dou Z and Berger SL. (2018) Cell Metabolism 27, 710-711

Dysregulation of the epigenetic landscape of normal aging in Alzheimer’s disease.
Nativio R, Donahue G, Berson A, Lan Y, Amlie-Wolf A, Tuzer F, Toledo J, Gosai S, Gregory BD, Torres C, Trojanowski JQ, Wang LS, *Johnson FB, *Bonini NM, *Berger SL. (2018). Nature Neuroscience, in press. *co-corr authors

Cytoplasmic chromatin triggers inflammation in senescence and cancer.
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. Nature. 2017 Oct 4. doi: 10.1038/nature24050. [Epub ahead of print]

Epigenetic Mechanisms of Longevity and Aging
Sen P, Shah PP, Nativio R, Berger SL. Cell. 2016 Aug 11;166(4):822-839. doi: 10.1016/j.cell.2016.07.050. Review.

MLL1 is Essential for the Senescence-Associated Secretory Phenotype.
Capell BC, Drake AM, Zhu J, Shah PP, Dou Z, Dorsey J, Simola DF, Donahue G, Sammons M, Rai TS, Natale C, Ridky TW, Adams PD, Berger SL. Genes Dev. 2016 Feb 1;30(3):321-36.

Autophagy mediates degradation of nuclear lamina.
Dou Z, Xu C, Donahue G, Shimi T, Pan JA, Zhu J, Ivanov A, Capell BC, Drake AM, Shah PP, Catanzaro JM, Ricketts MD, Lamark T, Adam SA, Marmorstein R, Zong WX, Johansen T, Goldman RD, Adams PD, Berger SL. Nature. 2015 Nov 5;527(7576):105-9.

H3K36 methylation promotes longevity by enhancing transcriptional fidelity.
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. Genes Dev. 2015 Jul 1;29(13):1362-76.