Denise S. O'Keefe, PhD
Assistant Professor of Urology
Dr. O'Keefe is a member of the Prostate and Urologic Cancer Program, and a member of the Cellular and Molecular Pathology Graduate Training Program.
Department of Urology
Suite G34, UPMC Shadyside
5200 Centre Avenue
Pittsburgh, PA 15232
Office Telephone: 412-623-3916
- PhD - 1996, University of Adelaide, Australia
Research InterestsThe most common molecular changes seen in prostate cancer are epigenetic (non-mutational) in nature, such as the hypermethylation of gene promoter sequences leading to transcriptional repression. In fact, more than 90% of prostate cancers exhibit alterations in the DNA structure of particular genes, resulting in the "switching-off" of a number of tumor-suppressor type genes. In addition, there are 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 lab investigates the potential mechanisms leading to these epigenetic changes to better understand the etiology of prostate cancer and thus develop novel tools for diagnosis, prognosis and treatment of the disease. Currently, our research is focused on modifying epigenetic behavior via nutritional means, for example dietary folate and folic acid. We are also studying the role of Prostate-Specific Membrane Antigen (PSMA), a folate hydrolase, to see how it affects folate uptake in cancer cells and other tissues of the body. More detailed and up-to-date information regarding all our lab projects can be found on our lab blog.
Selected PublicationsView Dr. O'Keefe's publications on PubMed
Bacich DJ, Sobek KM, Cummings JL, Atwood AA and O'Keefe DS. False Negative Results from using common PCR reagents. BMC Research Notes, Oct 2011. 4:457 (designated a "Highly Accessed article") PMID: 22032271
Tomaszewski, J.J., Cummings, J.L., Parwani, A.V., Dhir, R., Mason, J.B., Nelson, J.B., Bacich, D.J.*, O'Keefe, D.S.* (equal senior author). Increased cancer cell profliferation in prostate cancer patients with high levels of serum folate. The Prostate 2011, Sep;71(12):1287-93 PMID: 21308713.
Chang, G., Xu, S., Dhir, R., Chandran, U., O'Keefe, D.S., Greenberg, N.M. Gingrich, J.R. Hypoexpression and epigenetic regulation of candidate tumor suppressor gene CADM-2 in human prostate cancer. Clinical Cancer Research, 2010 16(22):5390-401. PMID: 21062931.
Yao, V., Berkman, CE., Choi, J., O'Keefe, D.S.* and Bacich, D.J.* Expression of Prostate-Specific Membrane Antigen (PSMA) increases cell folate uptake and proliferation and suggests a novel role for PSMA in the uptake of the non-polyglutamated folate, folic acid. The Prostate 2010, 70(3):305-16. (equal senior author) PMID: 19830782.
Bianco-Miotto, T., Hussey, D.J., Day, T.K, O'Keefe, D.S., Dobrovic, A. DNA methylation of the ABO promoter underlies loss of ABO allelic expression in a significant proportion of leukemic patients. PLoS ONE 2009, 4(3):e4788. PMID: 19274076.