Andrea Baccarelli

1995 - M.D., University of Perugia, Italy
2000 - M.P.H., University of Turin, Italy
2003 - Ph.D., University of Milan, Italy
2000-2004 Post-Doctoral Fellowship, National Cancer Institute, Bethesda, MD

My research focuses on identifying molecular and biological factors reflecting the impact of environmental exposures on human health, 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 pollutants, including particulate air pollution, airborne benzene, metals, pesticides, dioxin-like compounds, and persistent organic pollutants, which are known to be relevant to disease causation.

The epigenetic effects I have helped unveil can potentially modify health trajectories and affect disease risk. Although I have investigated a wide spectrum of environmental pollutants that produce various adverse effects on human health, my principal interest is in the effects of air pollution on cardiovascular and respiratory outcomes. 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 ischemic heart disease and stroke. I have been investigating the epigenetic effects of air pollution in studies of deep vein thrombosis in Milan, Italy, childhood asthma in Milazzo, Italy, cardiovascular disease in Boston, and in highly exposed populations in Beijing, China, Lublin, Poland, and Brescia, Italy, as well as in other study groups.

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 epidemiological 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.

To complement my research in epigenetics, I have conducted investigations to identify the influence of epigenetic changes at the gene expression level by evaluating mRNA transcripts that are related to environmentally responsive pathways. Since most of the epigenetic effects of environmental exposures that I have identified might be generated through oxidative stress, I have recently expanded my research to quantitatively measure oxidative stress-related biomarkers such as telomere length and mitochondrial mass in relation to environmental exposures, as well as their joint effects on disease outcomes. I have also been investigating genetic polymorphisms in genes that are critical to the metabolism of environmental pollutants, oxidative stress, and DNA repair to identify subset of subjects who have a genetic susceptibility to disease when exposed to specific environmental exposures.