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Summer Student Research Program Project Description FACULTY SPONSOR’S NAME AND DEGREE: Utz Herbig, Ph.D. PHONE: (973) 972 - 4426 DEPARTMENT AND INTERNAL MAILING ADDRESS:NJMS-UH Cancer Center, G1226 E-MAIL:[email protected] PROJECT TITLE (200 Characters max): Analysis of Cellular Senescence in Human Cancer Precursor Lesions HYPOTHESIS: Cellular senescence, a permanent, stable, and usually irreversible growth arrest has been studied in cultured cells for many years, however its biological role in preventing the progression of human cancer was only recently demonstrated. It now recognized that cellular senescence is a critical tumor suppressing mechanism preventing the proliferation of cells that have acquired potentially transforming mutations. Despite the recent discovery that human benign tumors and cancer precursor lesions are comprised of cells that had undergone cellular senescence, the reasons for cellular growth arrest in these lesions are poorly understood. Yet, this knowledge is critical in order to understand why cells within certain tumors remain inactive for the entire lifetime of an individual, escape this growth arrest on occasion to form malignant and metastatic tumors, or completely bypass this tumor suppressing mechanism giving rise to cancer. We hypothesize that a major contributing factor to cellular senescence in human cancer precursor lesions is dysfunction of telomeres, the physical ends of linear chromosomes. PROJECT DESCRIPTION (Include design, methodology, data collection, techniques, data analysis to be employed and evaluation and interpretation methodology) Fixed tumor tissue sections will be analyzed for the presence of specific markers of cellular senescence. These include dysfunctional telomeres, tumor suppressor proteins, and markers of heterochromatin. Techniques will include immunostaining, fluorescence in situ hybridization (FISH), and high magnification fluorescence microscopy of processed tissue. SPONSOR’S MOST RECENT PUBLICATIONS RELEVANT TO THIS RESEARCH: Herbig, U., Jobling, WA., Chen, BPC, Chen, DJ., and Sedivy, JM. 2004. Telomere shortening triggers replicative senescence of human cells through a signaling pathway involving ATM, p53 and p21CIP1 but not p16INK4a. Mol. Cell 14: 501-513. Herbig, U., and Sedivy, JM. 2006. Regulation of Growth Arrest in Senescence: Telomere Damage is Not the End of the Story. Mech. Ageing Dev. 127:16-24 Herbig, U., Ferreira, M., Condel, L., Carey, D., and Sedivy, J.M. 2006. Cellular Senescence in Aging Primates. Science 311: 1257 Jeyapalan, JC., Ferreira, M., Sedivy, JM., and Herbig, U. 2006. Accumulation of Senescent Cells in Mitotic Tissue of Aging Primates. Mech. Ageing Dev. 128: 36-44 IS THIS PROJECT SUPPORTED BY EXTRAMURAL FUNDS? Yes or No (IF YES, PLEASE SUPPLY THE GRANTING AGENCY’S NAME) Summer Student Research Program Project Description THIS PROJECT IS: Clinical Laboratory Behavioral Other THIS PROJECT EMPLOYS RADIOISOTOPES THIS PROJECT INVOLVES THE USE OF ANIMALS PENDING APPROVED IACUC PROTOCOL # THIS PROJECT INVOLVES THE USE OF HUMAN SUBJECTS PENDING APPROVED IRB PROTOCOL # M0120060337 WHAT WILL THE STUDENT LEARN FROM THIS EXPERIENCE? Basic research experience, planning and designing experiments, maintaining records of data, data analysis, data presentation, understanding of tumor suppressing mechanisms and cancer progression models.
