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Cellular Consequences of Telomere Shortening in Histologically Normal Breast Tissues

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Annual summary rept. 1 Sep 2009-31 Aug 2013

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My overall research goals are to further our understanding of the contribution of telomere biology in cancer development and progression and to use this knowledge to identify new biomarkers for the accurate prediction of cancer risk, early detection, and prognosis. Ideally, these biomarkers would have utility both at the population level and for an individual patient. As a basic scientist, I have been working to elucidate the mechanisms of tumor initiation and progression e.g telomere length alterations, as well as understanding how the interactions between the tumor and its tissue microenvironment may contribute to this process. Independent investigations, including from our own laboratory, have demonstrated the existence of cells with shortened telomeres in histologically normal tissues Meeker et al, 2004 Kurabayashi et al, 2008. In this proposal, we determined that telomere shortened normal cells occur in all breast specimens we assessed, even in the absence of a nearby tumor. In addition, we characterized the spectrum of cellular consequences of these telomere shortened normal cells. Furthermore, other telomere biology related studies were pursued involving exciting new data involving the Alternative Lengthening of Telomeres ALT pathway, a telomerase-independent telomere maintenance mechanism. In addition to the scientific investigations, this award has provided the trainee opportunities to interact with pathologists, oncologists, and epidemiologists to learn i normal and abnormal breast morphology, ii the strengths and limitations of currently used breast cancer biomarkers, iii current standards of breast cancer treatment, and iv the scientific rationale for ongoing clinical trials. These interactions have helped foster his future success as an independent translational breast cancer researcher.

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  • Medicine and Medical Research

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