DEPARTMENT OF UROLOGY

Denise O'Keefe, Ph.D.

  • Denise O'Keefe, Ph.D.  photoDenise O'Keefe, Ph.D.

    Associate Professor

    Email: okeefed@uthscsa.edu
    Telephone: 210-562-4098

     

     

     

    Biosketch

    Dr. Denise O'Keefe received her Bachelor of Science with honors in genetics from La Trobe University, Australia, and completed her doctorate in the Faculty of Medicine at the University of Adelaide, Australia in 1995. She then undertook postdoctoral studies in the field of genomic imprinting at Columbia University, before moving to Memorial Sloan-Kettering Cancer Center and later the Cleveland Clinic to study Prostate-Specific Membrane Antigen, a novel folate hydrolase. Dr. O'Keefe first established her own research laboratory at the University of Pittsburgh, moving to UT Health San Antonio in late 2014. Dr. O'Keefe has been continuously funded by the NIH and DOD since 2006 and regularly sits on study sections in addition to being an editorial board member of several journals. Having almost always been a basic scientist in a clinical department, Dr. O'Keefe has a long history of working with urology residents and fellows, as well as physicians to accomplish translational research goals.

    Education

    Ph.D., University of Adelaide, Australia (1995)
    B.S., La Trobe University Melbourne, Australia (1989)

    Research

    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. PSMA is also expressed in tumor neovasculature, most prominently in renal cell carcinoma, but also in particularly aggressive breast and brain tumors, among other solid tumors.  We have generated novel mouse models to study the role of PSMA in the vasculature of these tumors, and whether increase dietary folate my promote tumor progression when PSMA is present.

    Finally our most recently funded work involves the study of the metabolic reprogramming of the fatty-acid synthase gene by changes in dietary folate– this normally cytosolic protein translocates to the nucleus in a proportion of prostate cancer cells, where it is a marker of more aggressive disease.  Additionally, we are studying the mechanism by which nuclear FASN may promote epigenetic changes.

    Overall our goal is to better understand the etiology of prostate cancer so as to develop novel tools for diagnosis, prognosis and treatment, both nutritional and pharmacological, of the disease, and apply the findings to other cancers.

    List of Publications

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