Xue-Ru Wu

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Xue-Ru Wu

Professor, Department of Urology;Professor, Department of Pathology

Contact Info

423 East 23rd Street
New York, NY 10010



— Shanghai, Medical Education

Research Summary

Diseases involving the urinary bladder are of major clinical and social concerns. Bladder cancer is the fifth most common neoplasm and the twelfth leading cause of cancer deaths in the United States. Urinary tract infections are one of most common infectious diseases, accounting for 8-10 million physician''s visits annually. Together, these two diseases cost over 5 billion health care dollars in the clinical management. Despite extensive studies, little is known about the pathogenesis of these bladder disorders.

Our approach to better understand the molecular pathogenesis of bladder diseases is to utilize a group of bladder-specific markers?the uroplakins?that we have recently identified. These proteins, naturally forming two-dimensional crystals, are synthesized by all mammalian bladders studied, represent the major differentiation products of the normal bladder epithelium and are retained by a majority of the human bladder cancers. They are therefore excellent lineage-specific markers for bladder epithelium and for differentiating bladder cancers from cancers from other tissue origins. In addition, we have found that two of the uroplakins, uroplakins Ia and Ib, can serve as the major urothelial receptors for type 1-fimbriated E. coli, which cause more than 85% of the urinary tract infections. The preferential binding between a sub-population of E. coli that are predominant in urinary tract infection and uroplakins provides a molecular explanation for the recently recognized tissue tropism of uropathogenic E. coli. To study the bladder tumorigenesis, we have developed transgenic mouse models by specifically expressing activated oncogenes and mutated tumor suppressor genes in bladder epithelium. Mice harboring simian virus 40 large T oncogene, whose protein product inactivates p53 and retinoblastoma tumor suppressor protein, induced carcinoma in situ which progresses to invasive and metastatic transitional cell carcinomas. Mice harboring an activated H-ras induced bladder epithelial hyperplasia which progresses to superficial papillary tumors. These transgenic models provide strong experimental evidence that bladder cancers develop and progress via two distinctive pathways each of which is caused by unique genetic defects. Ongoing research efforts include the development of novel transgenic and knockout models, and the identification of molecular signatures of cancer progression through high-throughput screening, biochemical and cell biologic approaches.

Research Interests

Molecular Pathogenesis of Urinary Bladder Diseases

Tamm-Horsfall Protein Regulates Granulopoiesis and Systemic Neutrophil Homeostasis
Micanovic, Radmila; Chitteti, Brahmananda R; Dagher, Pierre C; Srour, Edward F; Khan, Shehnaz; Hato, Takashi; Lyle, Allison; Tong, Yan; Wu, Xue-Ru; El-Achkar, Tarek M
2015-01-04; 1046-6673,Journal of the American Society of Nephrology - id: 1420212, year: 2015 JOURNAL ARTICLE

Loss of FOXA1 Drives Sexually Dimorphic Changes in Urothelial Differentiation and Is an Independent Predictor of Poor Prognosis in Bladder Cancer
Reddy, Opal L; Cates, Justin M; Gellert, Lan L; Crist, Henry S; Yang, Zhaohai; Yamashita, Hironobu; Taylor, John A 3rd; Smith, Joseph A Jr; Chang, Sam S; Cookson, Michael S; You, Chaochen; Barocas, Daniel A; Grabowska, Magdalena M; Ye, Fei; Wu, Xue-Ru; Yi, Yajun; Matusik, Robert J; Kaestner, Klaus H; Clark, Peter E; DeGraff, David J
2015-05-04; 1525-2191,American journal of pathology - id: 1556562, year: 2015 Journal Article

Interstitial calcinosis in renal papillae of genetically engineered mouse models: relation to Randall's plaques
Wu, Xue-Ru
2015-02-05; 2194-7236,Urolithiasis - id: 1450422, year: 2015

A new tumor suppression mechanism by p27Kip1: EGFR down-regulation mediated by JNK/c-Jun pathway inhibition
Fang, Yong; Wang, Yihong; Wang, Yulei; Meng, Yan; Zhu, Junlan; Jin, Honglei; Li, Jingxia; Zhang, Dongyun; Yu, Yonghui; Wu, Xue-Ru; Huang, Chuanshu
2014-10-05; 0264-6021,Biochemical journal - id: 1283272, year: 2014 JOURNAL ARTICLE

Estrogen receptor alpha prevents bladder cancer via INPP4B inhibited akt pathway in vitro and in vivo
Hsu, Iawen; Yeh, Chiuan-Ren; Slavin, Spencer; Miyamoto, Hiroshi; Netto, George J; Tsai, Yu-Chieh; Muyan, Mesut; Wu, Xue-Ru; Messing, Edward M; Guancial, Elizabeth A; Yeh, Shuyuan
2014-10-05; 1949-2553,Oncotarget - id: 1283252, year: 2014 Journal Article