Carmen Sapienza, PhD

The long-term goals of the laboratory are to determine the relative contributions of genetic and environmental factors, including aging, to epigenetic variation in the human population and the role of this variation in human phenotypic diversity.

Because most common human diseases are thought to result from both heritable and environmental factors and their interaction, the laboratory seeks to determine whether environmental factors interact with an individual’s genome by altering epigenetic marks. One of the most potentially disruptive environments to which human beings are exposed is the in vitro culture conditions associated with assisted reproductive techniques (in vitro fertilization and intracytoplasmic sperm injection). Epidemiological studies suggest that children born through assisted reproduction are at substantially increased risk for several rare diseases associated with defects in epigenetic marking of the genome. We have demonstrated that children conceived in vitro have multiple DNA methylation and gene expression differences when compared with their in vivo-conceived counterparts. Such differences are modest in size but are also associated with important quantitative phenotypes, such as birth weight. We are continuing our epigenetic analysis of critical genes in the growth and insulin signaling pathways and examining their relationship to environmental variables intrinsic to in vitro conception.

We also have an interest in determining how the environment, including dietary factors, might contribute to colon cancer. We have demonstrated that the normal colon mucosa of cancer patients differs epigenetically from the colon mucosa of patients without cancer. Moreover, the genes that appear to be affected preferentially are those involved in lipid and carbohydrate metabolism and result in alterations in glucose metabolism and insulin signaling. These observations suggest a mechanistic connection between the observed association of obesity and high fat diets with colon cancer incidence. We are attempting to replicate these findings in additional patients, as well as test an animal model in which “metabolic syndrome” drugs may be tested for effects on the epigenotype.