Key words: gene-environment interactions, epigenetic reprogramming, genomic imprinting, germ cell and early embryonic development, methyl donor nutrients
The lab focus is to understand the mechanism of gene-environment interactions by examining the genetic basis of epigenetic response to nutrition and environmental toxicants. The goal is to identify and characterize genetic (naturally occurring and induced) and environmental (toxicant and nutritional) causes of DNA methylation disruption during embryonic development and to determine their aggregate role in disease.
DNA methylation is the most widely studied epigenetic modification. It is heritable and plays a major role genome-wide in gene expression regulation. However, it is also reversible causing it to be susceptible to disruptions that severely affect gene expression and phenotypic outcome. DNA methylation patterns in mammals undergo two required stages of reprogramming during development, in germ cells and preimplantation embryos, where genome-wide methylation is erased and reset. My research investigates molecular mechanisms by which nutrition and environment perturb DNA methylation states during these critical windows of development and how genetic makeup may confer susceptibility to such effects. Understanding how genes, nutrients, and environment interact to determine epigenetic states during development is crucial to determining an individual’s disease or fitness outcome and therefore key to defining effective preventative/treatment measures.
Ongoing areas of research:
Role of nutrition in determining epigenetic states. Nutrition is one of the most important but also one of the most variable components required for normal cellular function. Methyl donor nutrients such as folate, choline, betaine and Vitamin B12 are broken down to provide the major substrate for DNA methylation, S-adenosyl methionine (SAM). These studies aim to understand the role of methyl donor nutrients in establishment and maintenance of DNA methylation patterns required for normal gene regulation during development.
Epigenetic response to endocrine disrupting compounds (EDCs). Humans are widely exposed to EDCs and studies have shown an array of detrimental effects in endocrine pathways. However, they are also being increasingly scrutinized for a role in diseases unlinked to endocrine pathways where the mode of action is unclear. Vinclozolin is an EDC and fungicide used on both edible (i.e. wine grapes, canola) and nonedible (i.e. turf grass) vegetation. Rodent studies show typical antiandrogenic effects but also severe effects on DNA methylation at seemingly unrelated loci. Here, studies will examine epigenetic responses to vinclozolin during development as a model by which to dissect mechanisms of EDC disruption of DNA methylation and potential roles in disease.
Role of genetics in determining epigenetic response to exogenous factors. Genetic makeup including single nucleotide polymorphisms (SNPs), insertions/deletions and chromosomal rearrangements play a major role in phenotypic differences between individuals. These differences can occur naturally or by induction and can determine susceptibility or resistance to phenotypic outcome. The aim of these studies is to to identify and characterize cis and trans acting factors responsible for susceptibility to epigenetic change.
Please feel free to contact me by email or phone to discuss potential areas of my research where you would like to be involved or learn more.