|Department Affiliations||William Thomas Gerrard, Mario Anthony Duhon, and Jennifer and John Chalsty Professor of Urology, Department of Oncology|
|SOM Address||Room 115 Marburg Building|
Karen Sfanos 2003 – 2008
Dee Johng 2010
Our research is aimed at understanding the molecular genetic events responsible for initiation and progression of prostate cancer. We have taken advantage of the large clinical resource available in the Dept. of Urology at Johns Hopkins which specializes in treatment of prostate cancer to carry out studies of both sporadic and inherited forms of this common disease. In analysis of sporadic disease, a combination of molecular and cellular biologic techniques have been used to provide correlative and functional evidence for the existence of prostate tumor suppressor and oncogenes. Recent efforts have examined the role of alterations in the CHD1 chromatin remodeling gene, and MYC and PTEN in prostate cancer progression. To analyze inherited forms of prostate cancer, and to hopefully understand the molecular events responsible for the initiation of both inherited and sporadic prostate cancer, we have carried out GWAS studies to identify common prostate cancer risk SNPs in case control populations and linkage studies and candidate gene analyses identify more rare, high penetrance alleles in prostate cancer families. This latter approach has resulted in the identification of HOXB13 as the first prostate cancer specific susceptibility gene, and establishes homeobox genes as key determinants in prostate carcinogenesis. We anticipate that understanding the molecular genetics of prostate cancer will lead to better diagnostic and prognostic markers for prostate cancer (as a critical issue in this disease is the ability to accurately predict the aggressiveness of a given prostate cancer), and to identify new approaches for novel preventive and therapeutic strategies.
- Ewing CM, Ray AM, Lange EM, Zuhlke KA, Robbins CM, Tembe WD, Wiley KE, Isaacs SD, Johng D, Wang Y, Bizon C, Yan G, Gielzak M, Partin AW, Shanmugam V, Izatt T, Sinari S, Craig DW, Zheng SL, Walsh PC, Montie JE, Xu J, Carpten JD, Isaacs WB, Cooney KA. Germline mutations in HOXB13 and prostate-cancer risk. N Engl J Med. 2012 Jan 12;366(2):141-9. doi: 10.1056/NEJMoa1110000.
- Liu W, Xie CC, Thomas CY, Kim ST, Lindberg J, Egevad L, Wang Z, Zhang Z, Sun, J, Sun J, Koty PP, Kader AK, Cramer SD, Bova GS, Zheng SL, Grönberg H, Isaacs WB, Xu J. Genetic markers associated with early cancer-specific mortality following prostatectomy. Cancer. 2013 Jul 1;119(13):2405-12. doi: 10.1002/cncr.27954. Epub 2013 Apr 22. PubMed PMID: 23609948.
- Xu J, Zheng SL, Isaacs SD, Wiley KE, Wiklund F, Sun J, Kader AK, Li G, Purcell LD, Kim ST, Hsu FC, Stattin P, Hugosson J, Adolfsson J, Walsh PC, Trent JM, Duggan D, Carpten J, Grönberg H, Isaacs WB. Inherited genetic variant predisposes to aggressive but not indolent prostate cancer. Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2136-40. Epub 2010 Jan 11.
- Xu J, Lange EM, Lu L, Zheng SL, Wang Z, Thibodeau SN, Cannon-Albright LA, Teerlink CC, Camp NJ, Johnson AM, Zuhlke KA, Stanford JL, Ostrander EA, Wiley KE, Isaacs SD, Walsh PC, Maier C, Luedeke M, Vogel W, Schleutker J, Wahlfors T, Tammela T, Schaid D, McDonnell SK, DeRycke MS, Cancel-Tassin G, Cussenot O, Wiklund F, Grönberg H, Eeles R, Easton D, Kote-Jarai Z, Whittemore AS, Hsieh CL, Giles GG, Hopper JL, Severi G, Catalona WJ, Mandal D, Ledet E, Foulkes WD, Hamel N, Mahle L, Moller P, Powell I, Bailey-Wilson JE, Carpten JD, Seminara D, Cooney KA, Isaacs WB; International Consortium for Prostate Cancer Genetics. HOXB13 is asusceptibility gene for prostate cancer: results from the InternationalConsortium for Prostate Cancer Genetics (ICPCG). Hum Genet. 2013 Jan;132(1):5-14.doi: 10.1007/s00439-012-1229-4. Epub 2012 Oct 12. PubMed PMID: 23064873; PubMed Central PMCID: PMC3535370.
- Xu J, Kibel AS, Hu JJ, Turner AR, Pruett K, Zheng SL, Sun J, Isaacs SD, Wiley KE, Kim ST, Hsu FC, Wu W, Torti FM, Walsh PC, Chang BL, Isaacs WB. Prostate cancer risk associated loci in African Americans. Cancer Epidemiol Biomarkers Prev. 2009 Jul;18(7):2145-9. Epub 2009 Jun 23.