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overview Our group works at the intersection of genetic, molecular, and environmental epidemiology. We are interested in how genetic variation influences or alters the effects of environmental exposures and biomarkers on human health and biology. Areas of ongoing research include (1) dynamic features of the genome that are biomarkers of aging, exposure, and disease risk, (2) genetic susceptibility and response to exposure to arsenic, a known carcinogen (3) methods for assessing causal relationships among risk factors, biomarkers, and disease phenotypes, and (4) genetic contributors to prostate cancer disparities. The long-term goals of our work are to understand toxicity mechanisms and disease biology and to improve our ability to predict disease and target interventions to high-risk sub-populations. Several ongoing projects are described below: • Arsenic and the Human Genome: Susceptibility and response to exposure: Over 100 million people worldwide consume arsenic-contaminated drinking water, which increases risk for a wide array of health conditions, including cancer. The goal of this project is to identify features of the human genome, both inherited (i.e., SNPs) and acquired/dynamic (i.e., telomere length, DNA methylation, somatic mutations), that reflect susceptibility to arsenic toxicity or response to arsenic exposure, using data from a large arsenic-exposed Bangladeshi cohort. Achieving these goals will reveal biological mechanisms of toxicity and susceptibility and provide strategies for identifying high risk individuals. • Genetics of Arsenic Metabolism: fine mapping and analysis of rare variants: Susceptibility to arsenic toxicity is partially determined by genetic variants on chromosome 10 which influence individuals’ ability to metabolize arsenic. Dr. Pierce directs a project that will comprehensively characterize the effects of these variants across three arsenic-exposed population groups (Bangladeshis, American Indians, and European Americans). • Telomere Length and Chromosomal Instability Across Various Tissue Types: Age-related telomere shortening may play a critical role in susceptibility to common age-related diseases, including cancer. Using tissue samples from the NHGRI’s Gene-Tissue Expression project (GTEx), Dr. Pierce’s team is assessing correlations among telomere length measurements taken across many cancer-prone tissues and determining if telomere length is correlated with DNA damage, aging-related DNA methylation features, as well as inherited genetic variation. • Identifying DNA Methylation Features That Underlie Prostate Cancer Disparities: In light of racial disparities in prostate cancer incidence and mortality in the U.S., Dr. Pierce is leading a project to determine if DNA methylation patterns in prostate tissue differ between African American and Caucasian patients and how such differences are related to clinical features, as well as genetic and environmental factors. This work will contribute to the identification ethnicity-specific biomarkers for prostate cancer aggressiveness.

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