William B. Isaacs joined Johns Hopkins in 1977 as a lab technician for Donald Coffey, director of the Brady Urological Research Laboratory. He went on to receive his doctorate from The Johns Hopkins University in the Department of Pharmacology and Molecular Science. Dr. Isaacs then left Hopkins to do a post-doctoral program at the University of Iowa, but returned in 1988 to join the faculty of the Department of Urology.

Dr. William B. Isaacs research focus lies in hereditary prostate cancer.

Molecular genetics and cell biology of prostate cancer

Prostate cancer is the most commonly diagnosed malignancy in men in the United States, although our understanding of the molecular basis for this disease remains incomplete. We are interested in characterizing consistent alterations in the structure and expression of the genome of human prostate cancer cells as a means of identifying genes critical in the pathways of prostatic carcinogenesis. We are focusing on somatic genomic alterations occurring in sporadic prostate cancers, as well as germline variations which confer increases in prostate cancer risk. Both genome wide and candidate gene approached are being pursued, and cancer associated changes in gene expression analyses of normal and malignant prostate cells are being cataloged as a complementary approach in these efforts.

As an approach to identify high risk prostate cancer susceptibility alleles, we have identified a large number of families having multiple men affected with prostate cancer. Linkage analysis in these families has provided evidence of susceptibility genes located on chromosomes 1 and 8; RNASEL (1q24-25) and MSR1 (8p22) have been identified as candidate prostate cancer susceptibility genes on these chromosomes. The involvement of these genes in the innate immune system suggests an important role for genetic variability of host response in determining individual prostate cancer risk. Current efforts are aimed at characterizing the role of these genes in prostate carcinogenesis, and the identification of additional prostate cancer gene loci.

It is anticipated that this work will assist in providing more effective methodologies to identify men at high risk for this disease, in general, and in particular, to identify new markers of prognostic and therapeutic significance that could lead to more effective management of this common disease.