Research

Current Research Projects

Children's Environmental Health Research Center (NIEHS/EPA P01 Center)

Lifecourse Exposures & Diet Epigenetics, Maturation & Metabolic Syndrome. Our Center seeks to understand the mechanisms by which exposures to mixtures of EDCs (bisphenol A (BPA), phthalate metabolites, lead, and cadmium) in utero and during the pubertal transition affect physical growth and maturation and lead to alterations in metabolic homeostasis, oxidative stress and contribute to risk of metabolic syndrome.

Michigan Children's Center Website: https://sph.umich.edu/cehc/

TaRGET II (NIEHS U01 Grant)

Exposure Timing, Tissue and Cell Specific Epigenomics and Lifecourse Phenotypes. Toxicant exposures early in life adversely affect health outcomes later in life in animals and humans, in part due to epigenetic mechanisms, including DNA methylation. Many epigenetic epidemiology analyses are performed using biologically available DNA (e.g. blood, saliva, stool), which serve as proxies for epigenetic status in tissues targeted by exposures. Thus, the goal of the Target II U01 is to utilize an established mouse model of environmental exposures to evaluate tissue- and cell-specific epigenetic alterations associated with perinatal exposures and disease outcomes. Role: Principal Investigator

NIEHS Environmental Factor Blog on TarGET II: http://www.niehs.nih.gov/news/newsletter/2016/6/science-highlights/target/index.htm

TaRGET II Supplement for Whole Genome Bisulfite Sequencing (WGBS)

The University of Michigan site will oversee and conduct whole genome-bisulfite sequencing for the TaRGET II consortium. Role: Principal Investigator

Children's Health Exposure Analysis Resource (CHEAR, NIEHS U2C Center)

M-CHEAR Michigan Children's Health Exposure Analysis Resource Laboratory Hub. The M-CHEAR Hub will contribute to large-scale national efforts to advance our knowledge of the impact of the environment on children’s health by offering high-quality, state-of-the-art laboratory support for a wide variety of targeted and untargeted analyses in biological samples from external researchers conducting epidemiology & clinical studies. The Dolinoy Lab leads the Biological Response Indicators Resource (BRIR)

CHEAR Program Website: http://www.niehs.nih.gov/research/supported/exposure/chear/

NIH Director's Blog: Creative Minds: Building a Better RNA Toolbox: https://directorsblog.nih.gov/tag/pirna/

NIH Director's High Risk High Reward Transformative Award (NIEHS R01 Grant)

Development of piRNAs for target-specific methylation. The goal of this Transformative Award is to develop a suite of tools, based on the Piwi-interacting RNA (piRNA) mechanism, to accurately induce DNA methylation of targeted genes in adult tissues, applicable to all mammals.

NIEHS Environmental Factor Blog on piRNA project: http://www.niehs.nih.gov/news/newsletter/2015/11/science-dolinoy/

Environmental Health Core Center (NIEHS P30)

Michigan Center on Lifestage Environmental Exposures and Disease (M-LEEaD). Our mission is to promote translational research using novel multi-disciplinary approaches to better understand the impact of environmental exposures on risk of disease through mechanisms involving epigenetic modifications during vulnerable stages of life.

M-LEEaD Website: http://ehscc.umich.edu/

Nutrition and Obesity Core Center (NIDDK P30)

Michigan Nutrition Obesity Research Center. This NIDDK Core Center Grant is designed to inspire and support translational, multi-disciplinary research in obesity and nutrition, across the continuum of basic science to applications in individuals (medicine) and populations (public health).

M-Norc Website: http://mmoc.med.umich.edu/

Completed Research 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, completed)

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