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University of Maryland School of Medicine Division of Infectious Diseases

 
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Susan Keay, MD, PhD
Professor of Medicine

MD: Medical College of Wisconsin, 1982
PhD: Medical College of Wisconsin, 1981

Phone: (410) 605-6450
Fax: (410) 605-7837
E-mail: skeay@medicine.umaryland.edu
Address:
Veterans Affairs Medical Center
Medical Services
10 N. Greene Street
Room 3B-184
Baltimore, MD 21201

RESEARCH INTERESTS

Pathogenesis of interstitial cystitis.

In studies to determine the possible causes of IC, we have discovered two specific and significant findings: a factor that inhibits bladder epithelial proliferation, and altered levels of certain epithelial cell growth factors in the urine of IC patients.  The antiproliferative factor (or APF), which is made in the lower urinary tract of IC patients, has been purified and partially characterized, and its structure is being determined.  Additional studies to determine the significance of altered growth factor levels in this disease are in progress.

We have discovered an antiproliferative factor (APF) that is made specifically by bladder epithelial cells from patients with interstitial cystitis (IC), a chronic painful bladder disorder. APF inhibits bladder epithelial proliferation, and inhibits the production of HB-EGF by bladder epithelial cells. The structure of APF was determined by mass spectrometry, affinity chromatography and enzymatic digestion. APF is a glycopeptide whose peptide sequence bears 100% homology to the sixth transmembrane segment of frizzled eight. Additional studies to identify a receptor for APF, and to determine the mechanism whereby APF regulates HB-EGF production, are in progress.

We have also identified a fusion protein receptor for HCMV on human fibroblasts, and a partial functional receptor clone has been generated and sequence obtained.

RECENT PUBLICATIONS

Keay S, Zhang C-O, Shoenfelt J, Erickson DR, Whitmore K, Warren JW, Marvel R, Chai T. Sensitivity and Specificity of Antiproliferative Factor, Heparin-Binding Epidermal Growth Factor-Like Growth Factor, and Epidermal Growth Factor as Urine Markers for Interstitial Cystitis. Urology 2001; 57 (6 Suppl 1): 9-14.

Keay S, Zhang C-O, Shoenfelt JL, Chai TC. Decreased In Vitro Proliferation of Bladder Epithelial Cells from Patients with Interstitial Cystitis. Urology 2003; 61: 1278-1284.

Keay S, Seillier-Moiseiwitsch F, Zhang C-O, Chai TC, Zhang J. Changes in Human Bladder Cell Gene Expression Associated with Interstitial Cystitis or Antiproliferative Factor Treatment. Physiological Genomics 2003; 14: 107-115.

Keay S, Zhang C-O, Chai T, Warren J, Koch K, Grkovic D, Colville H, Alexander R. Antiproliferative Factor, Heparin-Binding Epidermal Growth Factor-Like Growth Factor, and Epidermal Growth Factor in Men with Interstitial Cystitis vs. Chronic Pelvic Pain Syndrome. Urology 2004; 63:22-6.

Keay SK, Szekely Z, Conrads TP, Veenstra TD, Barchi JJ, Jr., Zhang C-O, Koch KR, Michejda CJ. An Antiproliferative Factor from Interstitial Cystitis Patients is a Frizzled 8 Protein-Related Sialoglycopeptide. Proc. Natl. Acad. Sci,, USA 2004; 101:11803-11808.

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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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