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John W. Warren, MD Professor of Medicine
MD: Harvard University, 1970
Phone: (410) 706-7560
Fax: (410) 706-8700
E-mail: Jwarren@medicine.umaryland.edu
Address:
Division of Infectious Diseases University of Maryland School of Medicine 10 S. Pine St., MSTF 900 Baltimore, MD 21201
RESEARCH INTERESTS
Molecular pathogenesis of urinary tract infections (UTI) and pathogenesis, epidemiology, and genetics of interstitial cystitis.
PATHOGENESIS OF UTIs. Urinary tract infections are among the most common infections in humans and can be asymptomatic or cause cystitis, acute pyelonephritis, and blood stream invasion. About 80% of UTIs in otherwise normal hosts are caused by E. coli. In individuals with anatomically or functionally abnormal urinary tracts, the incidence of UTI is much higher and is caused by a wider spectrum of organisms; among these, Proteus mirabilis assumes importance not only because of its relatively high incidence and propensity for renal infection but especially because of its production of renal stones. Among patients with catheters or other foreign devices in the urinary tract, candida infections are becoming increasingly prominent. We are working: 1) to discover the mechanisms of pathogeneses of UTI caused by E. coli, P. mirabilis, and C. glabrata, and 2) to develop a clinically useful vaccine against P. mirabilis. Our strategy is to use the powerful tools of molecular biology and a well established mouse model of UTI to examine known virulence factors and, via new techniques including signature tagged mutagenesis and in vivo expression technology, heretofore unknown virulence factors. Similar resources will be used to develop candidate vaccines assembled from P. mirabilis subunits.
INTERSTITIAL CYSTITIS. Interstitial cystitis (IC) is a chronic bladder disease characterized by bladder pain, and urinary frequency and urgency. This distressing syndrome can last for years and its epidemiology, pathogenesis, and therapy are uncertain. Arguably, the most important void in our understanding of IC is its pathogenesis. We are using a two-fold approach to understand the pathogenesis of IC: 1) a case control study of IC seeking antecedent exposures which may be risk factors for the disease, and 2) establishment of a registry of families with several members with proven IC to search for the genes of susceptibility to this disease.
RECENT PUBLICATIONS
Island, MD, Cui, X., Foxman, B., Marrs, C.F., Stamm, W., Stapleton, A., Warren, J.W. Cytotoxicity of hemolytic, cytotoxic necrotizing factor 1-positive and -negative Escherichia coli to human T24 bladder cells. Infect. Immun. 1998; 66:3384-3389.
Johnson, D.E., Lockatell, C.V., Russell, R.G., Hebel, J.R., Island, MD, Stapleton, A., Stamm, W.E., Warren, J.W. Comparison of Escherichia coli strains recovered from human cystitis and pyelonephritis infections in transurethrally challenged mice. Infect. Immun. 1998; 66:3059-3065.
Keay, S., Zhang, C.-O., Hise, M.K., Hebel, J.R., Jacobs, S.C., Gordon, D., Whitmore, K., Bodison, S., Gordon, N., Warren, J.W. A diagnostic in vitro urine assay for interstitial cystitis. Urology 1998; 52:974-978.
Island, MD, Cui, X., Warren, J.W. Effect of Escherichia coli cytotoxic necrotizing factor 1 (CNF1) on repair of human bladder cell monolayers in vitro. Infect. Immun. 1999; 67:3657-3661.
Warren, J.W., Horne, L.M., Hebel, J.R., Marvel, R.P., Keay, S.K., Chai, T.C. Pilot study of sequential oral antibiotics in the treatment of interstitial cystitis. J. Urol. 2000; 163:1685-1688.
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To contact us:
Phone: 410-706-7560
Fax: 410-706-4619
E-mail: kvardjan@ihv.umaryland.edu
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