http://medicine.med.unc.edu/search/profile.aspx?ID=212
My lab is interested in the role of the Ink4a/Arf tumor suppressor locus in human cancer and aging. The products of this locus, p16INK4a and ARF, are potent anti-proliferative molecules that increase in expression with aging. Both molecules effect cell cycle arrest in particular inducing senescence, a potent form of permanent cell cycle arrest that is critical to preventing cancer. Recently, it has become clear from work in the mouse done in our lab and others that the expression of the Ink4a/Arf locus with aging serves not only to prevent malignancy, but untowardly limits the in vivo longevity of adult tissue-specific stem cells. Therefore, the Ink4a/Arf locus appears to contribute to human aging by inhibiting the replication of self-renewing cells in the adult organism, which in turn leads to age-related declines in the capacity of tissues to repair and regenerate. We believe that activity of the Ink4a/Arf locus is a major determinant of adult stem cell function with aging.
gastrointestinal cancer, cancer genetics, cancer and aging, p16INK4a, p14ARF, p53, tumor suppressor genes
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