The epigenetics of senescence, aging and cancer.

Chromatin assembly factories in senescence? Senescent cells stained to show DNA, blue; PML nuclear bodies, green; and histone chaperone HIRA, red. See Zhang et al, Mol Cell 2005.

The Adams lab investigates the impact of chromatin structure and epigenetics on cell proliferation, aging and diseases of aging, such as cancer. In particular, we are interested in age-associated epigenetic changes as contributors to cell, tissue and organismal aging. 

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Multiple factors likely conspire to drive the age-associated exponential increase in cancer incidence : mutations acquired during aging, congenital mutations and age-associated changes to more plastic and dynamic systems, such as the epigenome, metabolome, immunity, stem cell niche and many others. How these factors interact and their relative contribution, particularly to the earliest stages of cancer development and progression, are poorly understood.

While age is the biggest single risk factor for most cancers, the reason for this is currently poorly understood (link to Cancer and Aging for more details). We hypothesize that age-associated changes in chromatin structure, function and regulation contribute to the dramatic age-associated increase in incidence of cancer. Conversely, long term maintenance of cell phenotype and suppression of cancer presumably depends on a stable epigenetic program or “chromostasis”. 

 

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A benign melanocytic nevus, or mole, with fluorescently labeled nuclei (blue), nevus melanocytes (green) and β-catenin (red). Nevi are premalignant lesions that rarely progress to melanoma because the melanocytes have entered a non-proliferating senescent state. Jeff Pawlikowski in the lab investigated the molecular mechanisms that govern nevus formation and progression to melanoma, and showed that activation of the Wnt signaling pathway can potentiate nevus formation by delaying senescence. However, activated Wnt signaling in nevi may also promote nevus progression to melanoma. See Pawlikowski et al, PNAS 2013.

August 6, 2008 at 2:31 am