(Taken directly from the application) The overall objective of this program project is to develop a team consisting of investigators in the areas of epithelial biology, membrane biosynthesis, carcinogenesis and structural biology, that will interact closely and synergistically to study the cell and molecular biology and diseases of mammalian urothelium. Towards this long term goal, we will perform five interrelated projects focusing on a group of novel integral membrane proteins, the uroplakins, that form the urothelial plaques (also known as the asymmetrical unit membrane) that cover over 80% of the urothelial apical surface. These proteins represent excellent markers for terminally differentiated urothelial cells, and their genes are regulated in a urothelium-specific and differentiation-dependent fashion.
The aims of these five projects are to better understand: o What is the biological function of urothelial plaques, and how are the genes that encode the uroplakins regulated (Project 1)? o Once uroplakins are synthesized, how are they processed, assembled and targeted to the apical urothelial surface (Project 2)? o How do the uroplakin molecules interact with one another to form the 16-nm particles that naturally form two-dimensional crystalline arrays in urothelial plaques (Project 3)? o If we use uroplakin promoters to drive the expression of various oncogenes in urothelia of transgenic mice, what kinds of proliferative defects would we see (Project 4)?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Program Projects (P01)
Project #
3P01DK052206-05S1
Application #
6843695
Study Section
Special Emphasis Panel (ZDK1)
Program Officer
Mullins, Christopher V
Project Start
1999-03-01
Project End
2004-11-30
Budget Start
2002-12-01
Budget End
2004-11-30
Support Year
5
Fiscal Year
2004
Total Cost
$135,200
Indirect Cost
Name
New York University
Department
Dermatology
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
Chicote, Javier U; DeSalle, Rob; Segarra, José et al. (2017) The Tetraspanin-Associated Uroplakins Family (UPK2/3) Is Evolutionarily Related to PTPRQ, a Phosphotyrosine Phosphatase Receptor. PLoS One 12:e0170196
Norsworthy, Allison N; Pearson, Melanie M (2017) From Catheter to Kidney Stone: The Uropathogenic Lifestyle of Proteus mirabilis. Trends Microbiol 25:304-315
Wankel, Bret; Ouyang, Jiangyong; Guo, Xuemei et al. (2016) Sequential and compartmentalized action of Rabs, SNAREs, and MAL in the apical delivery of fusiform vesicles in urothelial umbrella cells. Mol Biol Cell 27:1621-34
Schaffer, Jessica N; Norsworthy, Allison N; Sun, Tung-Tien et al. (2016) Proteus mirabilis fimbriae- and urease-dependent clusters assemble in an extracellular niche to initiate bladder stone formation. Proc Natl Acad Sci U S A 113:4494-9
Kisiela, Dagmara I; Avagyan, Hovhannes; Friend, Della et al. (2015) Inhibition and Reversal of Microbial Attachment by an Antibody with Parasteric Activity against the FimH Adhesin of Uropathogenic E. coli. PLoS Pathog 11:e1004857
Liu, Yan; Mémet, Sylvie; Saban, Ricardo et al. (2015) Dual ligand/receptor interactions activate urothelial defenses against uropathogenic E. coli. Sci Rep 5:16234
Hickling, Duane R; Sun, Tung-Tien; Wu, Xue-Ru (2015) Anatomy and Physiology of the Urinary Tract: Relation to Host Defense and Microbial Infection. Microbiol Spectr 3:
Vieira, Neide; Deng, Fang-Ming; Liang, Feng-Xia et al. (2014) SNX31: a novel sorting nexin associated with the uroplakin-degrading multivesicular bodies in terminally differentiated urothelial cells. PLoS One 9:e99644
Desalle, Rob; Chicote, Javier U; Sun, Tung-Tien et al. (2014) Generation of divergent uroplakin tetraspanins and their partners during vertebrate evolution: identification of novel uroplakins. BMC Evol Biol 14:13
Mathai, John C; Zhou, Enhua H; Yu, Weiqun et al. (2014) Hypercompliant apical membranes of bladder umbrella cells. Biophys J 107:1273-9

Showing the most recent 10 out of 67 publications