My research focuses on identifying molecular and biological factors reflecting the impact of environmental exposures on cancer risk, with particular interest in epigenetics. Epigenetic marks, including DNA methylation, histone modifications, and non-coding RNAs, modify chromatin structure and gene expression without changing the underlying DNA sequence. Unlike genetic mutations, which represent rare events with permanent consequences on genes, epigenetic changes are reversible and responsive to environmental influences. Using a highly quantitative Pyrosequencing-based approach for DNA methylation analysis, I have been examining the effects on DNA methylation of a variety of environmental carcinogens, including particulate air pollution, airborne benzene, metals, pesticides, dioxin-like compounds, and persistent organic pollutants, which are known to be relevant to cancer etiology.
The epigenetic effects I have helped unveil can potentially modify health trajectories and affect cancer risk. I have recently demonstrated that Long interspersed nuclear element-1 (LINE-1), a sequence repeated up to half million times in the human genome, is peculiarly sensitive to demethylation in response to air pollution. I have also found that subjects with hypomethylated LINE-1 have higher incidence of and mortality from cancer. In addition, I have used epigenetic analysis to develop new biomarkers of cancer risk in case control studies on stomach cancer, prostate cancer, multiple myeloma, and leukemia. I have been investigating the epigenetic effects of environmental and occupational carcinogens, as well as the associations of epigenetic biomarkers with cancer risk, in studies in the U.S. and in several international studies in Italy, Poland, Russia, Oman, Mexico, Thailand, and China.
I am currently expanding my research in two complementary directions: 1) I am developing comprehensive investigations on multiple epigenetic mechanisms that cooperate to control gene expression. To this end, I have recently established in my laboratory methods for histone modifications and microRNA analysis that are amenable to use in human studies. I have recently used these methods to demonstrate that exposure to metal-rich particulate matter in a study of steel workers modified the levels of both histone modifications and microRNAs in blood leukocytes. 2) I have been taking advantage of recent technological advances that make possible to perform epigenome-wide analyses. I have piloted the use of microarray methods for DNA methylation analysis in investigations of air pollution and pesticide exposures that have the potential to open new research paths for unbiased methylomic mapping of environmentally-sensitive epialleles.