My research focuses on effect modifiers of metal toxicity including gene-environment interactions in neurodevelopment and in neurocognitive decline. The recognition that research in complex diseases particularly neurological diseases (neurodevelopment, Alzheimer’s, ADHD, Parkinson’s Disease etc) requires interdisciplinary approaches is evident in the NIH Roadmap Initiative.Research which only addresses environmental risk factors while ignoring the contributions of genetics (and vice verse) does not adequately address the biological underpinnings of neurologic diseases and at best provides only modest advances in our understanding of the disease etiology.

Early on, I focused my research training and my subsequent career in combining the state of the art research techniques in both environmental health and genetic epidemiology. My interest in doing so was spurred by the observation that while each discipline clearly had relevance to complex disease etiology, the findings of each field where not being incorporated by the other. For example, lead (and other metals) are clearly risk factors for neurodegeneration (Alzheimer’s Disease and Parkinson’s Disease) in particular, and genetic risk factors clearly exist for neurodegeneration, yet, little research sought to address the joint exposure to metals in the presence/absence of known genetic risk factors.

As an interdisciplinary scientist, I am bridging the communication gap between these fields and enabling and leading the design and conduct of sophisticated epidemiologic research in neurodevelopment. My goal is to bring a “Systems Biology” approach to epidemiologic research in which both environmental and genetic factors that determine brain development and degeneration are studied concurrently rather than in isolation.

I am presently studying metal exposures (Pb, Mn and As) as toxicants of interest because their mechanisms of action are well described, making candidate gene studies for gene by environment interaction more feasible.

I am the Principal Investigator on a NIH funded birth cohort in Tar Creek, Oklahoma, the site of a Superfund Toxic Waste site (manganese, arsenic and lead contamination), also known as the MATCH study (Metals Assessment Targeting Community Health). This is to my knowledge the first large scale study to determine the toxicity of developmental manganese and arsenic exposure in the United States. Eighty percent of the Tar Creek Superfund site is located on Native American land, and my pilot studies have shown increased exposure to Native Americans relative to the white community. I have been working with the local tribes and a community group to provide educational outreach on the risks of exposure to the general population of Tar Creek and have been assisting the tribes in determining exposure risks associated with a subsistence diet. I have formed partnerships with Indian Health Services and the local community hospital (Integris Baptist Regional Health Center) to facilitate recruitment of subjects. This type of partnership is particularly critical when proposing genetic research within a community. This project became the centerpiece of the new Harvard Center for Children’s Environmental Health, a newly funded program project grant and one of 11 such research centers across the country. I am also the PI of a new birth cohort in Mexico City funded by NIEHS. This is a collaborative project with the National Institute of Public Health, Mexico. Like MATCH, This study will also examine the role of Mn and As as predictors of child neurodevelopment and will address the role of psychosocial stress as a modifier of metal toxicity. This is a new endeavor and we are currently in the start-up phase of the project. I am also piloting studies on DNA methylation from peripheral blood DNA as a potential biomarker of effect from toxic metal exposure as well as the role of proteomics in predicting neurodevelopmental phenotypes.

Recently, I have assumed the role of Metals Core Research Director of the HSPH NIEHS Center Grant Program and co-directorship of the Metals Epidemiology Research Group. Dr. Hu(chair of Environmental Health at U of Michigan) and myself have established an inter-institutional collaborative research program. Our research program includes state of the art laboratory equipment for measuring multiple metals in both biological and environmental media, including a ICP/MS, atomic absorption spectrophotometry and a mercury analyzer, giving us sufficient throughput and capacity to service large epidemiologic studies. Our Xray fluorescence (XRF) laboratory can measure in vivo lead levels in bone, (a biomarker with a half-life measured in years) in adults and our team is piloting a newer, more sensitive XRF to measure bone lead levels in children.

M.D. M.P.H.