We are examining mechanisms of carcinogen susceptibility, which is the tendency to accumulate DNA lesions (i.e. DNA adducts) upon exposure to exogenous carcinogens. Despite the unquestionable contribution of carcinogen-induced mutagenesis to cancer, the relationship between carcinogen susceptibility and mutation has not been previously explored. Indeed, factors that regulate localized genomic carcinogen susceptibility have profound consequences in carcinogenesis by defining probabilities for mutation; thereby causing disparities throughout the genome that can impact genome stability and disease.
Chromatin-Regulated metabolic stability
We are investigating how chromatin modifiers coordinate metabolic homeostasis. The coordination of cellular function with the metabolic environment is essential for adaptation and survival. Failure to adapt can lead to cell death, developmental defects, and disease. Indeed, energy metabolism alterations are a major contributing factor for many pathologies, including cancer, cardiovascular disease, and diabetes, which together account for half of all deaths in most industrialized societies.
Adaptive cellular responses are often achieved by rapid inducible changes in gene expression programs. An ideal mechanism to achieve this is through modification of chromatin. Indeed, changes in chromatin architecture are known to regulate inducible gene expression in response to intra- and extracellular signals. Despite this knowledge, the mechanisms by which chromatin modification contributes to metabolic plasticity remain largely unexplored.