Fels Institute for Cancer Research and Molecular Biology, Temple University
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.