Completed Projects
The Role of Mixtures Exposures and Neurodevelopment (NIH Common Fund R21, completed)
Environmental exposures in early life: Epigenetics and neurodevelopment. This study explores epigenetic changes and neurodevelopmental outcome with real-life prenatal exposures (mixtures of pesticides, Pb, and ID) in two Chinese birth cohorts. The overarching hypothesis is that exposure mixtures are associated with changes in offspring DNA methylation patterns of key neurodevelopmental genes/pathways related to poorer neurocognitive function later in life
Environmental and Epigenomic Profiling of Pre-Adolescent Females in Rural Versus Urban Egyptian Populations (UM EHS Pilot Grant, completed)
Pre-pubertal females are particularly vulnerable to environmental influence on the epigenome due to mammary gland growth and differentiation. Similarly, genetic variation, such as single nucleotide polymorphisms (SNPs), can modify the toxicokinetics of chemical uptake, distribution, and elimination. Our overarching hypothesis is that epigenetic and genetic differences contribute to interindividual variation in BPA and phthalate exposure profiles. Building upon ongoing epidemiological and exposure studies in Gharbiah, Egypt, the two specific aims of this pilot project are: 1) Characterize pre-adolescent female exposure to BPA and phthalate metabolites and identify exposure-dependent epigenome-wide methylation patterns and 2) Evaluate the relationship between genetic variation in phase I xenobiotic metabolizing genes and BPA levels.
In Utero Exposure to Bisphenol A: Effects on the Fetal Epigenome (NIEHS ONES R01 Grant,
The overall objective of this grant application is to identify species, dose, and tissue-specific epigenome-wide alterations following gestational exposure to bisphenol a (BPA), a high production volume chemical used in the manufacturing of polycarbonate plastics and epoxy resins, and to map developmentally labile epigenetic genes in order to facilitate human health risk assessment and human disease prevention, diagnosis, and treatment.
Early Life Exposures and the Epigenome
Iron Deficiency
In collaboration with Barbara Felt from the UM Center for Human Growth and Development, this project aims to analyze the epigenetic dysregulation resulting from prenatal iron deficiency. Additionally, dose-response effects on physical and cognitive developmental milestones will be examined to understand the behavioral and physiological consequences of iron deficiency.
Lead Exposure
This project aims to understand the developmental effects of early life lead exposure, specifically related to early childhood growth and sexual maturation. Epigenomic analyses will be used in concert with an epidemiological approach in an effort to understand the molecular mechanisms linking exposure and biological consequences.
Oxidative Stress
In collaboration with Crag Harris, this pilot project aims to investigate how chemical teratogens and nutritional deficits affect DNA methylation through oxidative stress and redox regulation.
Alzheimer's Disease
Alzheimer's disease
This project combines comprehensive lead exposure measurements, APP-pathway gene-specific epigenetic approaches, and genome-wide epigenomic approaches in a novel investigation capitalizing on resources of the MADRC, the Michigan Claude D. Pepper Geriatrics Center, and the National Alzheimer’s Coordinating Center (NACC).
Life Course Exposures and the Epigenome
Mercury Exposure, DNA Methylation, and Cardiovascular Health
Methylmercury and inorganic mercury (Hg) are two prevalent toxicants (exposure sources: fish consumption and dental amalgams, respectively) that have the ability to alter the epigenome. Methylmercury has also been shown to adversely impact cardiovascular health. The objective of this study is to determine the impact of both methylmercury and inorganic Hg on DNA methylation, cardiovascular health, and metabolic outcomes in a cohort of dental professionals with environmental and occupational exposures from the American Dental Association (ADA, n=440). Associations between DNA methylation patterns and Hg exposure will be assessed by coupling an epigenome-wide platform (Illumina Infinium HumanMethylation450 BeadChip) with a quantitative candidate gene (pyrosequencing) approach. We further aim to evaluate DNA methylation as a mediator of relationships between Hg and cardiovascular and metabolic outcomes. Results are expected to improve risk assessment of methylmercury and inorganic Hg by increasing our understanding of the interplay between Hg, the DNA methylome, and precursors to cardiometabolic disease.