William G. Nelson V, MD, PhD, DSc

Professional Titles

• Director, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Marion I. Knott Director and Professor of Oncology

Primary Academic Title

Professor of Oncology

Background

Centers and Institutes

• Armstrong Institute for Patient Safety and Quality
• Brady Urological Institute
• Sidney Kimmel Comprehensive Cancer Center

Clinical Trial Keywords

prostate cancer

Videos

• William Nelson Discusses Tobacco Funds' Impact on Research

Recent News Articles and Media Coverage

• The Future of Personalized Cancer Medicine (CNN video)

  Interview with William G. Nelson, M.D., Ph.D (American Association for Cancer Research video)

  Epigenetics: A Symphony of Discovery | Science: Out of the Box

Additional Academic Titles

Professor of Radiation Oncology and Molecular Radiation Sciences, , Professor of Pharmacology and Molecular Sciences, Professor of Pathology, Professor of Medicine, Professor of Urology

Contact for Research Inquiries

Weinberg Building
401 N. Broadway Street
Baltimore, MD 21231

Phone: (410) 955-8822
Fax: (410) 955-6787

Research Interests

Cellular defenses against carcinogens, Cellular responses to DNA damage, DNA methylation and epigenetic gene silencing, Drug development, Inflammation and prostatic carcinogenesis, Prostate cancer, Urologic cancers

Lab Website

William G. Nelson Laboratory - Lab Website

• Normal and neoplastic cells respond to genome integrity threats in a variety of different ways. Furthermore, the nature of these responses are critical both for cancer pathogenesis and for cancer treatment. DNA damaging agents activate several signal transduction pathways in damaged cells which trigger cell fate decisions such as proliferation, genomic repair, differentiation, and cell death. For normal cells, failure of a DNA damaging agent (i.e., a carcinogen) to activate processes culminating in DNA repair or in cell death might promote neoplastic transformation. For cancer cells, failure of a DNA damaging agent (i.e., an antineoplastic drug) to promote differentiation or cell death might undermine cancer treatment. Our 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 carcinogens. Studies underway in the laboratory have been directed at characterizing the genomic abnormality further, and at developing methods to restore expression of epigenetically silenced genes and/or to augment expression of other carcinogen-defense enzymes in prostate cells as prostate cancer prevention strategies. 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.

Research Summary

Normal and neoplastic cells respond to genome integrity threats in different ways, and the nature of these responses is critical for both cancer pathogenesis and cancer treatment.

DNA-damaging agents activate several signal-transduction pathways in damaged cells, which trigger cell-fate decisions such as proliferation, genomic repair, differentiation and death.

In normal cells, failure of a DNA-damaging agent (i.e., a carcinogen) to activate processes culminating in DNA repair or cell death might promote neoplastic transformation. In cancer cells, failure of a DNA-damaging agent (i.e., an antineoplastic drug) to promote differentiation or cell death might undermine cancer treatment.

Dr. Nelson’s 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 inactivate the gene, making prostatic cells more vulnerable to carcinogens.

Current studies are directed at further characterizing the genomic abnormality and developing methods to restore expression of epigenetically silenced genes and/or to augment expression of other carcinogen-defense enzymes in prostate cells as prostate cancer prevention strategies.

Another major research interest 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 animal models, and monitoring the consequences on the development of PIA and prostate cancer.

PubMed

http://www.ncbi.nlm.nih.gov/pubmed?cmd=Search&term=Nelson%20WG

Selected Publications

• De Marzo AM, Nelson WG, Bieberich CJ, Yegnasubramanian S, "Prostate cancer: New answers prompt new questions regarding cell of origin." Nat Rev Urol. 2010 Dec;7(12):650-652.

• Haffner MC, Aryee MJ, Toubaji A, Esopi DM, Albadine R, Gurel B, Isaacs WB, Bova GS, Liu W, Xu J, Meeker AK, Netto G, De Marzo AM, Nelson WG, Yegnasubramanian S. "Androgen-induced TOP2B-mediated double-strand breaks and prostate cancer gene rearrangements." Nat Genet. 2010 Aug;42(8):668-675.

• Iwata T, Schultz D, Hicks J, Hubbard GK, Mutton LN, Lotan TL, Bethel C, Lotz MT, Yegnasubramanian S, Nelson WG, Dang CV, Xu M, Anele U, Koh CM, Bieberich CJ, De Marzo AM. "MYC overexpression induces prostatic intraepithelial neoplasia and loss of Nkx3.1 in mouse luminal epithelial cells." PLoS One. 2010;5(2):e9427.

• Lin J, Haffner MC, Zhang Y, Lee BH, Brennen WN, Britton J, Kachhap SK, Shim JS, Liu JO, Nelson WG, Yegnasubramanian S, Carducci MA. "Disulfiram is a DNA demethylating agent and inhibits prostate cancer cell growth." Prostate. 2011 Mar 1;71(4):333-343.

• Menke A, Guallar E, Rohrmann S, Nelson WG, Rifai N, Kanarek N, Feinleib M, Michos ED, Dobs A, Platz EA, "Sex steroid hormone concentrations and risk of death in US men." Am J Epidemiol. 2010 Mar 1;171(5):583-592.

Honors

• American Academy of Physicians, 1/1/14
• Sidney Kimmel Comprehensive Cancer Center Director's Award for Education, 1/1/04
• Parkway School District Hall of Fame Inductee, 1/1/04
• Sandoz Award for Outstanding Research in Pharmacology, Johns Hopkins University School of Medicine, 1/1/87
• Warfield T. Longcope Prize for Excellence in Clinical Medicine, Johns Hopkins University School of Medicine, 1/1/87
• Alpha Omega Alpha, Johns Hopkins University School of Medicine, 1/1/87
• Henry Strong Denison Award for Medical Research, Johns Hopkins University School of Medicine, 1/1/82
• National Council of Teachers of English Achievement Award in Writing, 1/1/76

Graduate Program Affiliations

• Pharmacology and Molecular Sciences,

  Cellular and Molecular Medicine

Memberships

• American Association of Cancer Research
• American Society of Clinical Oncology
• American Society of Microbiology
• Association for the Cure of Cancer of the Prostate (CaP CURE)

Professional Activities

• American Association of Cancer Research, Board of Directors
• American Board of Internal Medicine, Diplomate
• American Board of Internal Medicine, Diplomate
• National Coalition for Cancer Research, President
• Prostate Cancer Foundation, Scientific Advisory Board
• The V Foundation for Cancer Research, Scientific Advisory Committee