Assistant Professor of Environmental and Occupational Health, University of Pittsburgh
Maintenance of the genome is critical for the survival and health of an organism. Genomic mutations and alterations promote cancer, and the incidence of cancer increases exponentially with age. The Opresko lab is investigating the mechanisms of genomic instability associated with aging and diseases related to aging. Telomeres are a region of the genome that profoundly influences life span, human disease and genome integrity. Human telomeres are protein-DNA structures that preserve chromosome ends and limit the replicative potential of somatic cells. Increased loss of telomeric DNA and telomere dysfunction has been observed in several diseases associated with aging, in progeroid disorders, and after oxidative stress. The goals of the Opresko lab are to understand both the mechanisms of telomere loss and the cellular processes that preserve telomeric DNA. In order to visualize telomeres on human chromosomes we rely on fluorescent in situ hybridization techniques in which the telomeres are stained with a complementary peptide nucleic acid (PNA) probe. We are using complementary cellular biology and biochemical techniques to investigate the consequences of DNA damage on telomere structure and integrity, and the actions of proteins that protect and repair the telomeres. Currently, we are elucidating roles for the DNA repair protein WRN in preserving telomeres. Defects in the WRN protein causes the premature aging disorder Werner syndrome and accelerated loss of telomeric DNA. Given the critical role of telomeres in aging and cancer, understanding mechanisms of telomere loss and preservation should aid in the design of intervention therapies that prevent or delay the onset of aging-related diseases and cancer.
Lab Webpage: http://www.pitt.edu/~plo4/