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William Nelson, MD, PhD

Bill-Nelson
Department Affiliations Oncology, Urology, Pharmacology, Medicine, Pathology, and Radiation Oncology
Rank Professor
Office Phone 410-955-8822
Lab Phone
Fax 410-955-6787
Email bnelson@jhmi.edu
SOM Address Suite 1100 Weinberg Building
Website
Students

Bryon Lee 2001 – 2206

Jessica Gucwa 2007

Chris Weier 2009 – 2015

 

 

Research Interests

Our laboratory is dedicated to improving prostate cancer prevention and treatment via studies of the molecular pathogenesis of the disease. We have found that somatic inactivation of GSTP1, encoding a carcinogen-detoxification enzyme, by CpG island hypermethylation, likely initiates human prostatic carcinogenesis by increasing the vulnerability of prostate cells to genome damage mediated by electrophilic and oxidant carcinogens. GSTP1 is normally expressed in prostate basal epithelial cells, the stem cells for the prostatic epithelium, but not in columnar secretory epithelial cells. In proliferative inflammatory atrophy (PIA) lesions, the earliest precursors to prostatic intraepithelial neoplasia (PIN) and to prostate cancer, GSTP1 appears induced as part of a stress response associated with exposure to inflammatory oxidants. Loss of GSTP1 expression, attributable to GSTP1 CpG island hypermethylation, is characteristic of ~70% of PIN lesions and >90% of prostate cancers. Cancer cells devoid of GSTP1 accumulate more genome damage upon exposure to electrophilic carcinogens, such as those present in well-done or charred meats, or to oxidants.

Key research objectives under current scrutiny in the laboratory include: (i) elucidating the mechanism by which CpG island hypermethylation leads to GSTP1 gene silencing in prostate cancer cells, (ii) discovering the manner by which the GSTP1 CpG island accumulates abnormally methylated CpG dinucleotides, (iii) characterizing the phenotype of prostate cells deficient in GSTP1 activity, and (iv) exploring new avenues for prostate cancer prevention and treatment targeting DNA methyltransferases (DNMTs), 5-meC-binding domain proteins (MBDs), and carcinogen detoxification enzymes. Nakayama, M., Bennett, C.J., Hicks, J.L., Epstein, J.I., Platz, E.A., Nelson, W.G., and De Marzo, A.M. Hypermethylation of the human glutathione S-transferase-p gene (GSTP1) CpG island is present in a subset of proliferative inflammatory atrophy lesions but not in normal or hyperplastic epithelium of the prostate: a detailed study using laser-capture microdissection. Am J Pathol, 163: 923-933, 2003.

Publications

Research Profile

 

 

 

  • Haffner, M.C., Mosbruger, T., Esopi, D.M., Fedor, H., Heaphy, C.M., Walker, D.A., Adejola, N., Gürel, M., Hicks, J., Meeker, A.K., Halushka, M.K., Simons, J.W., Isaacs, W.B., De Marzo, A.M., Nelson, W.G., and Yegnasubramanian, S. Tracking the clonal origin of lethal prostate cancer.. Clin. Invest. 123: 4918-4922 (2013).*