Associate Professor of Environmental Epidemiology
Bldg 1, Rm G5
665 Huntington Ave, Boston, MA 02115
Phone: 617.432.0037 | Fax: 617.432.6913
My Laboratory of Human Environmental Epigenomics investigates the molecular mechanisms and biomarkers that reflect reprogramming of health and disease trajectories in response to environmental exposures. The laboratory research activities are specifically focused on epigenetics, mitochondriomics, and computational epigenomics.
The World Health Organization estimates that as much as 24% of global disease is caused by environmental exposures that can be averted. Yet, environmental causes of disease are not usually included in a patient’s standard clinical workup and often underappreciated even in primary and secondary prevention. In fact, while evidence of population-level effects of environmental exposures is overwhelming, a primary challenge in translating environmental health into clinical and preventive practices is the identification of individual risks. In the absence of costly and time-consuming prospective collections of exposure data, we have no means to identify individuals affected by environmental exposure and ascertain their risks.
To address this public health and research gap, I have been leading the use of novel molecular tools for epigenetics in environmental epidemiology. The mechanisms I investigate have unique properties: the epigenome is altered by the environment and such changes may persist over time even in the absence of the conditions that established them. These features are fundamental to reconstructing biological effects of exposures at the individual level and investigating environmental programming of disease. The initial three papers that I published in this area were first to show that pollutants produce changes in the human epigenome that are detectable in easy-to-obtain samples such as blood DNA. These findings sparked enormous interest in the field and led the way to many others epidemiology projects. One of those initial papers was named Classic Paper of the Year by Environmental Health Perspectives, the leading environmental health journal. My lab is currently conducting epigenome-wide association studies of DNA methylation on multiple cohorts at different life stages. Our team is actively participating in epigenetic consortia, such as CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) and PACE (Pregnancy And Child Epigenetics). We also have ongoing projects on non-coding RNAs, histone modification, and alternative forms of DNA methylation such 5-hydroxymethylation.
Health Trajectories and Programming of Future Disease Risks
The epigenetic effects I have helped unveil can potentially modify health trajectories and affect disease risk. My laboratory has shown that epigenetic alterations similar to those induced by environmental exposures can be used to predict the risk of highly common human diseases, including cardiovascular disease, respiratory disease, and cancer. Recent and ongoing projects investigate effects from environmental exposures, including particulate air pollution, metals, Bisphenol A, phthalates, and pesticides, and common risk factors, such as psychosocial violence, second-hand smoking, and maternal diet and metabolic alterations. My laboratory has been conducting studies on the U.S. population, as well as in highly-exposed groups or special conditions of exposure at several international locations in China, Canada, Mexico, Italy, Israel, Poland, Thailand, Oman, Bulgaria, Russia, and other countries.
Most of the epigenetic effects of environmental exposures that I have identified might be generated through oxidative stress. Not only mitochondria are a primary target of environmental oxidative damage, but most importantly damaged mitochondria become a main source of intra-cellular oxidation. Due to the paucity of repair mechanisms, mitochondrial DNA is expected to accumulate oxidative damage and thus provide a molecular archive of past environments and aggregate risk. Consistent with this hypothesis, we recently showed that air pollution and lead increase the blood abundance of mtDNA molecules, a marker of damaged, dysfunctional mitochondrial DNA, by up to 50%. Following these exciting results, I have established a program of environmental mitochondriomics in my lab. We propose that mitochondria are uniquely sensitive to environmental toxics. If successful, our research in mitochondriomics will identify new non-invasive methods to reconstruct past exposures and identify individuals at risk of developing disease. Because of the central roles of oxidation and mitochondria in environmental causation of disease, mitochondriomics could provide models that can be applied to a variety of risk factors and health-related conditions.
Computational methods and quantitative genomics play an increasing role in providing effective approaches to analyzing and summarizing epigenetic and molecular data. Computational tools are critical not only to directing the selection of key experiments, but also in formulating new testable hypotheses through detailed analysis of complex molecular information that is not achievable using traditional approaches alone. The Harvard T.H. Chan School of Public Health is taking a leading role in interdisciplinary research involving the computational analysis of complex relationships between genes and their environment as well as basic biological and quantitative sciences. My lab has recently developed A-clustering – a novel, high effective method for “epigenetic haplotyping” of DNA methylation and data reduction. A-clustering reduces multiple testing, optimizes statistical power and allows for the identification of epigenetic signals that would be otherwise undetected. The laboratory is dynamically involved in the activity of the Computational Epigenomics Working Group (coordinated by Dr. Lin and Dr. Baccarelli), which is dedicated to developing and applying novel approaches for genome-scale epigenomic analysis. Recent activity included establishing a standardized enhanced pipeline for bioinformatic and biostatistical analysis of 450K Methylation BeadChip data, as well as for sequencing data.
Education and Training
1995 – M.D., University of Perugia, Italy
2000 – M.P.H., University of Turin, Italy
2003 – Ph.D., University of Milan, Italy
2000-2004 – Postdoctoral Fellowship, National Institutes of Health, Bethesda, MD