The principal goal of our research program is to determine the underlying molecular mechanisms that link an abnormal intrauterine milieu to the later development of diseases such as obesity, type 2 diabetes, cognitive defects and cerebral palsy after birth.
We have established a number of animal models in the rodent including intrauterine growth retardation, maternal obesity, maternal exposure to high fructose corn syrup, and maternal exposure to endocrine disruptors. All of these animal models induce obesity, beta-cell and hepatic dysfunction in the offspring ultimately leading the development of obesity and fasting hyperglycemia. Using these different animal models we are elucidating the role of epigenetic mechanisms (DNA methylation, histone modifications, non-coding RNAs) in the development of an abnormal phenotype in the offspring in the ß-cell, liver, fat, and brain. Using next generation sequencing, we are assessing how an altered maternal milieu impacts the epigenome and the transcriptome and the underlying molecular mechanisms that induce genome-wide epigenetic modifications.
The focus of the second project is to define the effects of obesity on the oocyte and early embryo. Utilizing early embryo transfer techniques, we have determined that obesity in pregnancy induces a number of defects in the offspring as early as the 2-cell embryo stage. Many of these defects can be traced back to the oocyte. Current studies are also exploring possible interventions such as an antioxidant diet or a methyl donor diet to determine whether the effects of an aberrant intrauterine milieu can be reversed after birth. The goals of the third project are to determine whether there are differences in outcome with respect to onset of puberty and obesity after exposure early in life or during intrauterine development to high fructose corn syrup versus sucrose or glucose. We are studying the interaction between the metabolome and the microbiome to determine the molecular mechanisms linking high fructose corn syrup ingestion to the later development of obesity.