Research in my laboratory is focused on the causes, treatment, and prevention of bladder cancer. Bladder cancer is among the most common cancers in the United States. Initial and recurrent bladder tumors develop due to mutation of DNA in the cells that line the interior bladder wall. The DNA mutations lead to abnormal protein function and amounts, and ultimately un-regulated cell growth. One of these proteins, DBCCR1, is known to be important in the development of bladder cancer but the actual function of DBCCR1 is unknown. The laboratory has recently demonstrated an association between DBCCR1 and another protein, ASML3a. The amount of ASML3a is increased in bladder tumors relative to normal bladder tissue, and thus it may prove to be a way to detect or treat bladder cancer.

One of the great strengths of the laboratory is expertise in cytometric techniques, both image analysis and flow cytometry. Prior work applied these techniques to the study of clinical specimens from bladder cancer patients and we showed that single cell measurements of DNA content and determination of chromosome copy number, and gene copy number by fluorescence in situ hybridridization were both diagnostic and prognostic for bladder cancer. Our studies on DBCCR1 employed imaging of single cells over time to demonstrate DBCCR1 mediated cell death, the first phenotype attributed to this putative tumor suppressor gene.

We are developing an animal model of bladder cancer for use in studying bladder tumorigenesis and for testing various treatment and prevention strategies. In this transgenic mouse model we have introduced a gene into mouse embryos that will allow us to precisely control other genes in the mouse bladders by adding the antibiotic doxycycline to their drinking water. Thus abnormal proteins, proteins that we believe will cause bladder tumors; can be switched on and off. This precise control will allow us to study the development of bladder cancer at the very earliest stages and devise sensitive detection methods and refine treatment regimens.

The expertise developed in the study of bladder cancer has recently been applied to the study of interstitial cystitis (IC). IC is an inflammatory condition of the bladder. Individuals with IC suffer from urinary frequency, urgency, and abdominal pain. The etiology is unknown. The laboratory is studying exfoliated cells in urine from IC patients enrolled in an IC clinical trial. DNA cytometry has demonstrated changes in cellular proliferation patterns in IC patients. Additionally we are investigating the function of a substance found in the urine of IC patients that has anti-proliferative activity in vitro.

Borhan A, Reeder JE, O'Connell MJ, Wright KO, Wheeless LL, di Sant'Agnese PA, McNally ML, Messing EM. Grade progression and regression in recurrent urothelial cancer. Journal of Urology, in press, 2003.

Wright KO, Messing EM, Reeder JE. DBCCR1 mediates death in cultured bladder tumor cells. Oncogene, in press, 2003.

Wright KO, Messing EM, Reeder JE. Increased expression of the acid sphingomyelinase-like protein ASML3a in bladder tumors. J Urol 2002 Dec;168(6):2645-9.

Jung I, Reeder JE, Cox C, Siddiqui JF, O'Connell MJ, Collins L, Yang Z, Messing EM, Wheeless LL. Chromosome 9 monosomy by fluorescence in situ hybridization of bladder irrigation specimens is predictive of tumor recurrence. J Urol 1999 Dec;162(6):1900-3

Reeder JE, O'Connell MJ, Yang Z, Morreale JF, Collins L, Frank IN, Messing EM, Cockett AT, Cox C, Robinson RD, Wheeless LL. DNA cytometry and chromosome 9 aberrations by fluorescence in situ hybridization of irrigation specimens from bladder cancer patients. Urology 1998 May;51(5A Suppl):58-61.

Reeder JE, Morreale JF, O'Connell MJ, Stadler WM, Olopade OF, Messing EM, Wheeless LL. Loss of the CDKN2A/p16 locus detected in bladder irrigation specimens by fluorescence in situ hybridization. J Urol 1997 Nov;158(5):1717-21.

Reeder JE, Cox C, Wheeless LL, Flint A, Liebert M, Grossman HB. Variability of DNA analysis by image cytometry. Bladder Tumor Marker Network Cytometry 1997 Jun 1;28(2):176-80.

References are to the PubMed publications list. PubMed is maintained by the National Library of Medicine and provides abstracts of publications as well as links to the full text of many articles (at journal homepages).