Faculty Profile

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) and of histone modifications and their enzymes in cancer progression. Thus, a degradation of the epigenome occurs which may lead to a field of cancer susceptibility in the prostate serving as a marker for the disease as well as a potential avenue for therapy.

• Yang B, Wagner J, Damaschke N, Yao T, Wuerzberger-Davis SM, Lee MH, Svaren J, Miyamoto S, Jarrard DF. A Novel Pathway Links Oxidative Stress to Loss of Insulin Growth Factor-2 (IGF2) Imprinting through NF-κB Activation. PLoS One. 2014 Feb 18;9(2): PubMed PMID: 24558376; PubMed Central PMCID: PMC3928145.
• Damaschke NA, Yang B, Blute ML Jr, Lin CP, Huang W, Jarrard DF. Frequent Disruption of Chromodomain Helicase DNA-Binding Protein 8 (CHD8) and Functionally Associated Chromatin Regulators in Prostate Cancer. Neoplasia. 2014 Dec;16(12):1018-27 PubMed PMID: 25499215.