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William G. Nelson
Department Affiliation: Primary: Oncology; Secondary: Urology; Pharmacology and Molecular Sciences; Medicine; Pathology; Radiation Oncology and Molecular Radiation Sciences
Joint: Environmental Health Sciences
Degree: M.D., Ph.D., Johns Hopkins University
Rank: Professor and Director
Telephone Number: 410-955-8822
Fax Number: 410-955-6787
School of Medicine Address: Suite 1100 Weinberg Building, 401 N. Broadway Street, Baltimore, MD 21231
DNA methylation and epigenetic gene silencing; inflammation and prostatic carcinogenesis.
I run a laboratory jointly with Srinivasan Yegnasubramanian. The laboratory has discovered the most common known somatic genome alteration in human prostatic carcinoma cells. The DNA lesion, hypermethylation of deoxycytidine nucleotides in the promoter of a carcinogen-defense enzyme gene, appears to result in inactivation of the gene and a resultant increased vulnerability of prostatic cells to oxidants and to carcinogens. Studies underway in the laboratory have been directed at characterizing the epigenome abnormality further, and at discovery new small molecule inhibitors and drugs to restore expression of epigenetically silenced genes.
Another major interest pursued in the laboratory is the role of chronic or recurrent inflammation as a cause of prostate cancer. Genetic studies of familial prostate cancer have identified defects in genes regulating host inflammatory responses to infections. A newly described prostate lesion, proliferative inflammatory atrophy (PIA), appears to be an early prostate cancer precursor. Current experimental approaches feature induction of chronic prostate inflammation in laboratory mice and rats, and monitoring the consequences on the development of PIA and prostate cancer.
Mian, O.Y., Khattab, M.H., Hedayati, M., Coulter, J., Abubaker-Sharif, B., Schwaninger, J.M., Veeraswamy, R.K., Brooks, J.D., Hopkins, L., Shinohara, D.B., Cornblatt, B., Nelson, W.G., Yegnasubramanian, S., and DeWeese, T.L. GSTP1 loss results in accumulation of oxidative DNA base damage and promotes prostate cancer cell survival following exposure to protracted oxidative stress. Prostate 76: 199-206, 2016. Pub Med Reference
Murtola, T., Gurel, B., Umbehr, M., Lucia, M.S., Thompson, I.M., Jr, Goodman, P.J., Kristal, A.R., Parnes, H.L., Lippman, S.M., Sutcliffe, S., Peskoe, S.B., Barber, J.R., Drake, C.G., Nelson, W.G., De Marzo, A.M., and Platz, E.A. Inflammation in benign prostate tissue and prostate cancer in the finasteride arm of the Prostate Cancer Prevention Trial. Cancer Epidemiol. Biomarkers Prev. 25: 463-469, 2016. Pub Med Reference
Munari, E., Chaux, A., Vaghasia, A.M., Taheri, D., Karram, S., Bezerra, S.M., Gonzalez-Roibon, N., Nelson, W.G., Yegnasubramanian, S., Netto, G.J., and Haffner, M.C. Global 5-hydroxymethylcytosine levels are profoundly reduced in multiple genitourinary malignancies. PLoS One 11: e0146302, 2016. Pub Med Reference
Anders, N.M., Liu, J., Wanjiku, T., Giovinazzo, H., Zhou, J., Vaghasia, A., Nelson, W.G., Yegnasubramanian, S., and Rudek, M.A. Simultaneous quantitative determination of 5-aza-2'-deoxycytidine genomic incorporation and DNA demethylation by liquid chromatography tandem mass spectrometry as exposure-response measures of nucleoside analog DNA methyltransferase inhibitors. J. Chromatogr. B. 1022: 38-45, 2016. Pub Med Reference
Mattox, A.K., Wang, Y., Springer, S., Cohen, J.D., Yegnasubramanian, S., Nelson, W.G., Kinzler, K.W., Vogelstein, B., and Papadopoulos, N. Bisulfite-converted duplexes for the strand-specific detection and quantification of rare mutations. Proc. Natl. Acad. Sci. USA 114: 4733-4738, 2017. Pub Med Reference
Platz, E.A., Kulac, I., Barber, J.R., Drake, C.G., Joshu, C.E., Nelson, W.G., Lucia, M.S., Klein, E.A., Lippman, S.M., Parnes, H.L., Thompson, I.M., Goodman, P.J., Tangen, C.M., and De Marzo, A.M. A prospective study of chronic inflammation in benign prostate tissue and risk of prostate cancer: linked PCPT and SELECT cohorts. Cancer Epid. Biom. Prev. 26: 1549-1557, 2017. Pub Med Reference
Haffner, M.C., Taheri, D., Luidy-Imada, E., Palsgrove, D.N., Eich, M.L., Netto, G.J., Nirschi, T.R., Zheng, Q., Hicks, J.L., Nelson, W.G., De Marzo, A.M., Marchionni, L., Drake, C.G., and Yegnasurbamanian, S. Hypomethylation, endogenous retrovirus expression, and interferon signaling in testicular germ cell tumors. Proc. Natl. Acad. Sci. USA 115: E8580-E8582, 2018. Pub Med Reference
Giovinazzo, H. Walker, D., Wyhs, N., Liu, J., Esopi, D.M., Vaghasia, A.M., Jain, Y., Bhamidipati, A., Zhou, J., Nelson, W.G., and Yegnasubramanian, S. A high-throughput screen of pharmacologically active compounds for inhibitors of UHF1 reveals epigenetic activity of anthracyclene derivative chemotherapy drugs. Oncotarget 10: 3040-3050 , 2019. Pub Med Reference
Other graduate programs in which Dr. Nelson participates:
Cellular and Molecular Medicine Graduate Program