The Jarrard laboratory group is focused on several
understudied aspects of tumor biology.
One question addresses the role of epigenetics and prostate cancer susceptibility with aging. The epigenome is susceptible to modulation by many factors associated with aging, including dietary and oxidative stress. We have found that the peripheral zone of the prostate from men with prostate cancer commonly contains biallelic Igf2 expression (Clin Can Res 1996), and that an age-related degradation of imprinting occurs in the murine and human prostate (JBC 2007: Can Res 2009). A loss of CTCF binding protein during aging underlies the relaxation in Igf2 imprinting seen during aging (Prostate 2011) and furthermore is accelerated with oxidative stress linking the environment to epigenetic changes (Plos One 2014). This has led to a broader study of DNA methylation alterations as biomarkers for cancer (Neoplasia 2013; J Urol 2014). Thus, a degradation of the epigenome occurs which leads to a field of cancer susceptibility in the prostate serving as a marker for the disease as well as a potential avenue for therapy. Other areas of research involve characterizing histone modifications and their enzymes in cancer progression allowing a personalized medicine approach to prostate cancer therapy.
A second area of research focuses on the role cellular senescence plays in cancer and its involvement in cancer progression. Current efforts include identifying novel small molecules that induce senescence, pathways involved in senescence, and markers of this phenotype in vivo (JBC 2005; Br J Ca 2008: J Biomol Screen 2009; JNCI 2011). As a response to cancer therapy, including androgen deprivation a common treatment in prostate cancer, senescence may occur and play a role in patient responses (Prostate 2013).
David F Jarrard, MD also serves as PI on several national clinical trials and brings a translational cancer focus to the program.