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DNA Repair Unit Michele K. Evans, M.D., Senior Scientist |
| Biography: Dr. Michele K. Evans, a board certified internist and a medical oncologist, received her medical degree from the University of Medicine and Dentistry of New Jersey-The Robert Wood Johnson Medical School in Piscataway. She received her postgraduate training in internal medicine at Emory University School of Medicine and fellowship training in medical oncology within the Medicine Branch of the Clinical Oncology Program at the National Cancer Institute (NCI). She became a Senior Clinical Investigator in the Laboratory of Molecular Pharmacology, NCI and then moved to the NIA where her research interest centers on the clinical implications of eukaryotic DNA repair in cancer pathogenesis and aging. She also conducts epidemiologic work in the area of health disparities. In addition, Dr. Evans serves as Acting Scientific Director, NIA. |
| Research:DNA repair mechanisms are believed to play a vital role in the maintenance of genome integrity. Loss of fidelity in the replicative mechanism, accumulation of genetic lesions, and faulty DNA repair mechanisms facilitate tumorigenesis. Similarly, aging or cellular senescence is characterized by random accumulation of damage or mutation in DNA, RNA, or proteins and perhaps a diminished ability to repair DNA. The increased incidence of cancer as a function of age underscores the mechanistic relatedness of these two cellular processes. The diminished ability to repair DNA appears to be the crucial and convergent factor highlighting the important clinical manifestations associated with defects in DNA repair mechanisms. The overall thrust of our work has been to understand the role of DNA repair in cellular senescence and tumorigenesis in order to uncover ways to use measured DNA repair capacity as a clinical tool in the diagnosis and treatment of cancer and age-related disease and disability. |
Interaction of Human 8-oxoguanine-DNA Glycosylase with Novel Binding Partners: Human 8-oxoguanine-DNA glycosylase (OGG1) is the major enzyme for repairing 7-8, dihydro-8-oxoguanine (8-oxoG), a pre-mutagenic guanine base lesion produced by reactive oxygen species (ROS). The mutagenicity of 8-oxoG lies in its propensity to mispair with adenine during DNA replication. The importance of 8-oxoG and its repair by OGG1 are underscored by the frequent absence of the OGG1 allele in human lung tumors and the increased incidence of lung tumors in mice lacking a functional OGG1. It is important to determine the factors that influence the repair ability of OGG1 as defective activity may lead to increased mutations in genes that cause diseases. We are currently investigating novel binding partners of OGG1 and determining the functional and biochemical significance of these interactions. Our recent results suggest that binding of OGG1 to a DNA damage protein plays a key role in the cellular response to oxidative stress and DNA damage. |
The relationship of oxidative DNA damage, oxidative stress markers and inflammatory markers in a human population. We have analyzed the baseline levels of oxidative DNA damage and assessed the DNA damage profiles of participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) cohort. We recently improved a protocol to examine different DNA damage parameters in a human population. Using this assay, we found that age, sex and race all impact the single stand repair capacity in humans. Furthermore, current analyses include correlations with relevant biomarkers of inflammation and oxidative stress. |
MicroRNAs and human aging. microRNAs (miRNAs) are small non-coding (~22 nt) RNAs that incorporate into the miRNA-induced silencing complex (RISC) and typically negatively regulate gene expression through mRNA degradation, translation inhibition or by performing both functions. We profiled the expression of over 800 miRNAs in peripheral blood mononuclear cells from young and old individuals in the HANDLS study by real-time RT-PCR analysis and found that the majority of miRNAs are downregulated with human age. Furthermore, we identified that the expression of several targets of these age-related miRNAs change in abundance with age. Therefore, changes in the expression of miRNAs and their predicted targets occur with the aging process, and may have the potential to be diagnostic indicators of age or age-associated diseases. |
| PubMed: Search for listing of Dr. Evans publications. |
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