Dr. Denise O’Keefe
researches the role of folate in the initiation and progression of
prostate cancer. The most common molecular changes seen in prostate cancer are
epigenetic (non-mutational) in nature, such as the hypermethylation of gene
promoter sequences leading to changes in gene expression. Folate, which is both found in the diet in
its natural form and as the artificial folic acid in fortified foods such
as breads and cereals, is part of the one-carbon pathway, which supplies the
methyl groups responsible for nearly all biological methylation reactions in
the cell, including DNA, RNA, and histone methylation. We are studying the effect different dietary
levels of folate or folic acid have on prostate cancer or other cancer-related
cells, to determine if there are possibly different dietary recommendations
that could be made for patients at risk for, or whom have cancer.
Another related project
we have running looks at the mechanism(s) by which PSMA (Prostate-Specific
Membrane Antigen) promotes prostate cancer progression. PSMA is a folate hydrolase, and allows cells
expressing it to take up more folate, which is needed for methylation
reactions, as well as cell proliferation.
We are also studying other epigenetic changes frequently seen in
prostate tumors that allow expression of the so called “junk DNA” in our
genome, which causes disruption of the nuclear structure and subsequent ectopic
expression of these “retrotransposons,” likely resulting in ectopic expression
of growth-promoting genes, and repression of growth regulating genes.
Our goal is to
investigate the potential mechanisms leading to these epigenetic changes to
better understand the etiology of prostate cancer and develop novel tools for
diagnosis, prognosis and treatment of the disease, and apply the findings to
To see a list of publications, click here.