Untitled Document

Research

David F. Jarrard

M.D., University of Virginia
Professor, Departments of Surgery and Molecular and Environmental Toxicology
jarrard@surgery.wisc.edu

Modulation of genomic imprinting with aging

Our basic research laboratory is focused on the role of epigenetics in aging and prostate cancer. Many environmental aspects, such as oxidative stress, diet, and hormonal influences, may affect epigenetic marks at imprinted loci. We are currently investigating alterations in imprinting in both an in vitro human prostate epithelial cell model and in vivo in a mouse model of aging. We theorize that a loss of imprinting of IGF-II, a growth factor, contributes to the development of prostate cancer with aging. DNA methylation is a putative regulatory mechanism underlying these alterations in imprinting.

Representative Publications
Teng, J., Wang, Z.Y., Jarrard, D.F., & Bjorling, D.E. (2008). Roles of estrogen receptor alpha and beta in modulating urothelial cell proliferation. Endocr. Relat. Cancer, 15(1), 351-64.

Fu, V.X., Dobosy, J.R., Desotelle, J.A., Almassi, N., Ewald, J.A., Srinivasan, R., Berres, M., Svaren, J., Weindruch, R., & Jarrard, D.F. (2008). Aging and cancer-related loss of insulin-like growth factor 2 imprinting in the mouse and human prostate. Cancer Research, 68(16), 6797-680.

Dobosy, J.R., Fu, V.X., Desotelle, J.A., Srinivasan, R., Kenowski, M.L., Almassi, N., Weindruch, R., Svaren, J., & Jarrard, D.F. (2008). A methyl-deficient diet modifies histone methylation and alters Igf2 and H19 repression in the prostate. Prostate, 68(11), 1187-119.

Ewald, J., Desotelle, J., Almassi, N., & Jarrard, D. (2008). Drug-induced senescence bystander proliferation in prostate cancer cells in vitro and in vivo. Br. J. Cancer, 98(7), 1244-9.

Dobosy, J.R., Roberts, J.L.W., Fu, V.X., & Jarrard, D.F. (2007). The expanding role of epigenetics in the development, diagnosis, and treatment of prostate cancer and benign prostatic hyperplasia. J. Urol., 177(3), 822-31.

Best, S., Sawers, Y., Fu, V.X., Almassi, N., Huang, W., & Jarrard, D.F. (2007). Integrity of prostatic tissue for molecular analysis after robotic-assisted laparoscopic and open prostatectomy. Urology, 70(2), 328-32.

Johnson, A.R., Munoz, A., Gottlieb, J.L., & Jarrard, D.F. (2007). High dose zinc increases hospital admissions due to genitourinary complications. J. Urol., 177(2), 639-43.

Kibel, A.S., Rosenbaum, E., Kattan, M.W., Picus, J., Dreicer, R., Klein, E.A., Chatta, G.S., Nelson, J.B., DiPaola, R.S., Roth, B.J., Cookson, M.S., Wilding, G., Jarrard, D.F., et al. (2007). Adjuvant weekly docetaxel for patients with high risk prostate cancer after radical prostatectomy: a multi-institutional pilot study. J. Urol., 177(5), 1777-81.

Saleem, M., Adhami, V.M., Zhong, W., Longley, B.J., Lin, C.Y., Dickson, R.B., Reagan-Shaw, S., Jarrard, D.F., Mukhtar, H. (2006). A novel biomarker for staging human prostate adenocarcinoma: overexpression of matriptase with concomitant loss of its inhibitor, hepatocyte growth factor activator inhibitor-1. Cancer Epidemiol. Biomarkers Prev., 15(2), 217-27.

Faith, D., Han, S., Lee, D.K., Friedl, A., Hicks, J.L., De Marzo, A.M., Jarrard, D.F. (2005). p16 is upregulated in proliferative inflammatory atrophy of the prostate. Prostate, 65 (1), 73-82.

Schwarze, S.R., Luo, J., Isaacs, W.B., Jarrard, D.F. (2005). Modulation of CXCL14 (BRAK) expression in prostate cancer. Prostate, 64(1), 67-74.

Schwarze, S.R., Fu, V.X., Kenowski, M.L., Jarrard, D.F. (2005). The identification of senescence-specific genes during the induction of senescence in prostate cancer cells. Neoplasia, 7(9), 816-823.

Fu, V.X., Schwarze, S.R., Kenowski, M.L., Leblanc, S., Svaren, J., Jarrard, D.F. (2004). A loss of insulin-like growth factor-2 (IGF2) imprinting is modulated by CTCF downregulation at senescence in human epithelial cells. J. Biol. Chem., 279(50), 52218-52226.

Atwood, C.S., Barzilai, N., Bowen, R.L., Brown-Borg, H.M., Jarrard, D.F., Fu, V.X., Heilbronn, L.K., Ingram, D.K., Ravussin, E., Schwartz, R.S., & Weindruch, R. (2003). Pennington scientific symposium on mechanisms and retardation of aging. Experimental Gerontology, 38(10), 1217-1226.

Schwarze, S.R., Fu, V.X., & Jarrard, D.F. (2003). Cdc37 enhances proliferation and is necessary for normal human prostate epithelial cell survival. Cancer Research, 63(15), 4614-4619.

Schwarze, S.R., DePrimo, S.E., Grabert, L.M., Fu V., Brooks, J.D., & Jarrard, D.F. (2002). Novel pathways associated with bypassing cellular senescence in human prostate epithelial cells. Journal of Biological Chemistry, 277(17), 14877-14883.

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