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David Jarrard

David F. Jarrard

M.D., University of Virginia
Professor, Department of Urology

Investigation of the epigenetic basis underlying aging-related cancers

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 including DNA methylation and 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 have found 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 that is dictated by the chromatin protein CTCF. Levels of CTCF, involved in gene activation, repression and the formation of boundary elements, decrease with aging and result in widespread DNA methylation changes that alter chromatin architecture. These changes predispose to cancer formation and represent a target for chemoprevention during aging.

Representative Publications
Blute, M. L., Jr., Damaschke, N., Wagner, J., Yang, B., Gleave, M., Fazli, L., ... Jarrard, D. F. (2017). Persistence of senescent prostate cancer cells following prolonged neoadjuvant androgen deprivation therapy. PLoS One, 12(2), e0172048.
View publication via DOI: DOI:10.1371/journal.pone.0172048

Blute, M. L., Jr., Shiau, J. M., Truong, M., Shi, F., Abel, E. J., Downs, T. M., & Jarrard, D. F. (2017). A biopsy-integrated algorithm for determining gleason 6 upgrading risk stratifies risk of active surveillance failure in prostate cancer. World Journal of Urology, 35(5), 729-735.
View publication via DOI: DOI:10.1007/s00345-016-1933-0

Blute, M. L., Jr., Ziemlewicz, T. J., Lang, J. M., Kyriakopoulos, C., Jarrard, D. F., Downs, T. M., ... Abel, E. J. (2017). Metastatic tumor burden does not predict overall survival following cytoreductive nephrectomy for renal cell carcinoma: A novel 3-dimensional volumetric analysis. Urology, 100, 139-144.
View publication via DOI: DOI:10.1016/j.urology.2016.09.016

Blute, M. L., Jr., Zorn, K., Grimes, M., Shi, F., Downs, T. M., Jarrard, D. F., ... Abel, E. J. (2016). Extreme obesity does not predict poor cancer outcomes after surgery for renal cell cancer. BJU International, 118(3), 399-407.
View publication via DOI: DOI:10.1111/bju.13381

Grimes, M. D., Blute, M. L., Jr., Wittmann, T. A., Mann, M. A., Zorn, K., Downs, T. M., ... Jarrard, D. F., ... Abel, E. J. (2016). A critical analysis of perioperative outcomes in morbidly obese patients following renal mass surgery. Urology, 96, 93-98.
View publication via DOI: DOI:10.1016/j.urology.2016.06.018

Heninger, E., Krueger, T. E., Thiede, S. M., Sperger, J. M., Byers, B. L., Kircher, M. R., ... Jarrard, D. F., ... Lang, J. M. (2016). Inducible expression of cancer-testis antigens in human prostate cancer. Oncotarget, 7(51), 84359-84374.
View publication via DOI: DOI:10.18632/oncotarget.12711

Jarrard, D. F., & Huang, W. (2016). The new age of molecular taxonomy approaches. European Urology, 69(4), 561-562.
View publication via DOI: DOI:10.1016/j.eururo.2015.11.011

Kelcz, F., & Jarrard, D. F. (2016). Prostate cancer: The applicability of textural analysis of MRI for grading. Nature Reviews Urology, 13(4), 185-186.
View publication via DOI: DOI:10.1038/nrurol.2016.33

Yang, B., Damaschke, N., Yao, T., McCormick, J., Wagner, J., & Jarrard, D.F. (2015). Pyrosequencing for the accurate quantification of imprinting expression. Journal of Cellular Biochemistry, 116(7):1165-70.
View publication via DOI: DOI:10.1002/jcb.25081

Blute, M.L.Jr., Damaschke, N.A., & Jarrard, D.F. (2015). The epigenetics of prostate cancer diagnosis and prognosis: update on clinical applications. Current Opinion in Urology, 25(1):83-8.
View publication via DOI: DOI:10.1097/MOU.0000000000000132

Abel, E. J., Heckman, J. E., Hinshaw, L., Best, S., Lubner, M., Jarrard, D. F., Downs, T. M., Nakada, S. Y., Lee Jr, F. T., Huang, W., & Ziemlewicz, T. (2015). Multi-quadrant biopsy technique improves diagnostic ability in large heterogeneous renal masses. The Journal of Urology, 194(4), 886-891.
View publication via DOI: DOI:10.1016/j.juro.2015.03.106

Blute, M. L., Jr., Abel, E. J., Downs, T. M., Kelcz, F., & Jarrard, D. F. (2015). Addressing the need for repeat prostate biopsy: New technology and approaches. Nature Reviews Urology, 12(8), 435-444.
View publication via DOI: DOI:10.1038/nrurol.2015.159

Blute, M. L., Jr., Rushmer, T. J., Shi, F., Fuller, B. J., Abel, E. J., Jarrard, D. F., & Downs, T. M. (2015). Renin-angiotensin inhibitors decrease recurrence after transurethral resection of bladder tumor in patients with nonmuscle invasive bladder cancer. Journal of Urology, 194(5), 1214-1219.
View publication via DOI: DOI:10.1016/j.juro.2015.05.104

Sweeney, C. J., Chen, Y. H., Carducci, M., Liu, G., Jarrard, D. F., Eisenberger, M., ... DiPaola, R. S (2015). Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. New England Journal of Medicine, 373(8), 737-746.
View publication via DOI: DOI:10.1056/NEJMoa1503747

Keil, K.P., Abler, L.L., Laporta, J., Altmann, H.M., Yang, B., Jarrard, D.F., Hernandez, L.L., & Vezina, C.M. (2014). Androgen receptor DNA methylation regulates the timing and androgen sensitivity of mouse prostate ductal development. Developmental Biology, 396(2):237-45.
View publication via DOI: DOI:10.1016/j.ydbio.2014.10.006

Damaschke, N.A., Yang, B., Blute, M.L.Jr, Lin, C.P., Huang, W., & Jarrard, D.F. (2014). Frequent Disruption of Chromodomain Helicase DNA-Binding Protein 8 (CHD8) and Functionally Associated Chromatin Regulators in Prostate Cancer. Neoplasia, 16(12):1018-27.
View publication via DOI: DOI:10.1016/j.neo.2014.10.003

Yang, B., Wagner, J., Damaschke, N., Yao, T., Wuerzberger-Davis, S.M., Lee, M.H., Svaren, J., Miyamoto, S., & Jarrard, D.F. (2014). A Novel Pathway Links Oxidative Stress to Loss of Insulin Growth Factor-2 (IGF2) Imprinting through NF-KB Activation. PLoS One, 9(2).
View publication via DOI: DOI:10.1371/journal.pone.0088052

Damaschke, N. A., Yang, B., Bhusari, S., Svaren, J. P., & Jarrard, D. F. (2013). Epigenetic susceptibility factors for prostate cancer with aging. Prostate, 73(16), 1721-1730.
View publication via DOI: DOI:10.1002/pros.22716

Yang, B., Bhusari, S., Kueck, J., Weeratunga, P., Wagner, J., Leverson, G., . . . Jarrard, D. F. (2013). Methylation profiling defines an extensive field defect in histologically normal prostate tissues associated with prostate cancer. Neoplasia, 15(4), 399-408.
View publication via DOI: DOI:10.1593/neo.13280

Ewald, J. A., Desotelle, J. A., Church, D. R., Yang, B., Huang, W., Laurila, T. A., & Jarrard, D. F. (2013). Androgen deprivation induces senescence characteristics in prostate cancer cells in vitro and in vivo. Prostate, 73(4), 337-345.
View publication via DOI: DOI:10.1002/pros.22571

Ewald, J. A., & Jarrard, D. F. (2012). Decreased skp2 expression is necessary but not sufficient for therapy-induced senescence in prostate cancer. Translational Oncology, 5(4), 278-287.

Bhusari, S., Yang, B., Kueck, J., Huang, W., & Jarrard, D.F. (2011). Insulin-like growth factor-2 (IGF2) loss of imprinting marks a field defect within human prostates containing cancer. The Prostate, 71, 15, 1621-30.
View publication via DOI: DOI:10.1002/pros.21379

Bhusari, S.S., Dobosy, J.R., Fu, V., Almassi, N., Oberley, T., & Jarrard, D.F. (2010). Superoxide dismutase 1 knockdown induces oxidative stress and DNA methylation loss in the prostate. Epigenetics, 5(5), 402-409.
View publication via DOI: DOI:10.4161/epi.5.5.11853

Ewald, J.A., Desotelle, J.A., Wilding, G. & Jarrard, D.F. (2010). Therapy-Induced Senescence for Cancer. Journal of the National Cancer Institute, 102(20), 1536-154.
View publication via DOI: DOI:10.1093/jnci/djq364

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.
View publication via DOI: DOI:10.1158/0008-5472.CAN-08-1714

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.
View publication via DOI: DOI:10.1002/pros.20782

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.
View publication via DOI: DOI:10.1038/sj.bjc.6604288

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.
View publication via DOI: DOI:10.1677/erc.1.01255

Kibel, A., Eisenberger, M., Picus, J., Dreicer, R., Klein, E., Roth, B., Cookson, M., Wilding, G., Jarrard, D., Salavaggione, L., & Watson, M. (2008). Gene expression profiling for the prediction of therapeutic response to adjuvant docetaxel for high risk localized prostate carcinoma. The Journal of Urology, 179(4), 47.
View publication via DOI: DOI:10.1016/S0022-5347(08)60142-1

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.
View publication via DOI: DOI:10.1016/j.juro.2006.10.063

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.
View publication via DOI: DOI:10.1016/j.urology.2007.04.005

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.
View publication via DOI: DOI:10.1016/j.juro.2006.09.047

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.
View publication via DOI: DOI:10.1016/j.juro.2007.01.028

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.
View publication via DOI: DOI:10.1158/1055-9965.EPI-05-0737

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.
View publication via DOI: DOI:10.1002/pros.20258

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.
View publication via DOI: DOI:10.1002/pros.20215

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.
View publication via DOI: DOI:10.1593/neo.05250

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.
View publication via DOI: DOI:10.1074/jbc.M405015200

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.
View publication via DOI: DOI:10.1016/j.exger.2003.08.005

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.
View publication via DOI: DOI:10.1074/jbc.M200373200

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