Judith Campisi Senior Staff Scientist JCampisi@lbl.gov Mailstop: 70A-1118 The primary goal of my laboratory is to understand the cellular and molecular basis of aging. Our primary focus is the aging of mammalian cells that have the ability to divide in culture and in tissues. The principal projects in this area aim to: 1) identify the molecular mechanisms responsible for the cell cycle arrest and altered differentiation that is the hallmark of senescent human cells; 2) use cell culture models and transgenic mouse models to understand the consequences of cell senescence for tissue function and integrity; 3) determine the mechanisms by which DNA damage and inappropriate mitogenic stimuli induce senescent-like phenotypes in culture and in vivo; 4) understand how the RecQ helicases, which are defective in premature aging syndromes, maintain genomic stability and postpone cell senescence and organismic aging; 5) determine the components and structure of the human telomere, the mechanisms by which telomere length is regulated, and the mechanisms by which telomere length regulates the senescent phenotype; 6) understand how cell senescence suppresses tumorigenesis, and the molecular basis for the close relationship between cancer and aging. A second goal of my laboratory is to understand the mechanisms responsible for the normal, premalignant and malignant phenotypes of breast epithelial cells. The principal projects in this area are to understand the transcriptional mechanisms that determine breast epithelial cell phenotypes, and the role of nuclear organization in breast epithelial cell behavior. Recent Publications: Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I, Pereira-Smith O, Peacocke M, Campisi J. (1995) A novel biomarker identifies senescent human cells in culture and aging skin in vivo. Proc. Nat'l Acad. Sci. USA 92: 9363-9367. Campisi J. (1996) Replicative senescence: An old lives tale? Cell 84: 497-500. Dimri GP, Nakanishi M, Desprez PY, Smith JR, Campisi J. (1996) Inhibition of E2F activity by the p21 inhibitor of cyclin-dependent protein kinases in cells expressing or lacking a functional retinoblastoma protein. Molec. Cell. Bio. 16: 2987-2997. Campisi J. (1997) Aging and cancer: The double-edged sword of replicative senescence. J. Am. Geriatrics Soc. 45: 1-6. Huang S, Li B, Gray MD, Oshima J, Mian S, Campisi J. (1998) The premature aging syndrome protein WRN is a 3' to 5' exonuclease. Nature Genetics 20: 114-116. Desprez PY, Thomasset N, Lin CQ, Sympson CJ, Bissell MJ, Campisi J. (1998) A novel pathway for mammary epithelial cell invasion induced by the helix-loop-helix protein Id-1. Molec. Cell. Bio. 18: 4577-4588.