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Project

Generating molecular markers that selectively label urothelial sub-populations

Funder: National Institute of Diabetes and Digestive and Kidney Diseases

Funding period
USD 1.6 M
Funding amount
Abstract
DESCRIPTION (provided by applicant): The urinary outflow tract, including the renal pelvis, ureters, bladder and upper urethra, is lined by a specialized stratified epithelium called the urothelium, composed of a basal layer, an intermediate layer and a superficial layer consisting of umbrella cells. Umbrella cells are large multinucleated cells that are specialized for synthesis and trafficking of Uroplakins, a family of secreted proteins that assemble into the crystallin plaque lining the apical surface ofthe urothelium that generates a leak-proof barrier between the urine and the blood. The urothelium can be rendered dysfunctional by damage, or disease, including interstitial cystitis, inflammation and UTI, but at present there is no way to repair/regenerate this tissue. In addition the urothelium is thought to be a source of stem/progenitor cells that give rise to different forms of bladder cancer. One impediment to progress has been the paucity of markers distinguishing urothelial sub-types including progenitors We propose to generate a collection of genetic markers specific for urothelial sub-populations beginning with those that we have defined using transgenic and lineage-tagged mouse models expressing RFP or GFP. In addition to umbrella cells and basal cells, we have been able to define a novel cell type that resides in the intermediate layer that is a likely umbrella cell progenitor. Flow sorted cell populations will be genetically profiled by the Potter/Aronow labs using RNA-Seq, a technique that they have successfully used to expression profile kidney cell types. Once validated candidates are in hand, we will map their distribution in the LUT using in situ hybridization and immunohistochemistry. We will also map the distribution of existing candidates identified in GUDMAP1 as potentially urothelial-cell specific. We have been part of the GUDMAP1 consortium for the past 3 years, and during this time we have successfully generated LUT-focused expression data which has been incorporated into the existing alas. The relationships that we have developed with GUDMAP collaborators and experience with expression analysis in the LUT will be an advantage as we undertake the proposed studies.

 
95
Projects
USD 74.9 M
Aggregated funding amount
USD 1.1 M
Average funding amount
Project list item
Roles of epigenetic regulators in bladder cancer progression

University of California - Cancer Research Coordinating Committee to Zhu Wang

USD 74,960
2020 - 2020
Project list item
Engineering Smart Solutions for Disorders of the Bladder Urothelium

Engineering and Physical Sciences Research Council

 
2019 - 2023
Project list item
Transdifferentiation of fibroblasts to urothelial progenitors for definitive urothelial replacement therapy in non-muscle invasive bladder cancer

Bladder Cancer Advocacy Network to Philip A Beachy, Kris Butalid Prado

USD 300,000
2019 - 2021
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Role of Fgfr2 signaling in bladder injury and regeneration

National Institute of Diabetes and Digestive and Kidney Diseases to CARLTON MATTHEW BATES

USD 234,750
2019 - 2022
Project list item
[Clinicopathological and molecular analyses of precursor lesions of urothelial carcinoma] - Original in Japanese

Japan Society for the Promotion of Science to Shin-ichi MURATA, 生笛 松崎

USD 39,492
2019 - 2022
Project list item
Cell-biological mechanisms of the urinary bladder multifocal tumor formation (postdoctoral research project)

Slovenian Research Agency to Jerman Urška Dragin

 
2019 - 2021
Project list item
Regulation of Bladder Umbrella Cell Paracellular Permeability by Stretch

National Institute of Diabetes and Digestive and Kidney Diseases to AMITY FENN EATON

USD 77,959
2018 - 2019
Project list item
Challenging dogma: an alternative non-hierarchical, epigenetically regulated model of the urothelium.

Biotechnology and Biological Sciences Research Council to Andrew Feber

USD 468,019
2018 - 2021
Project list item
Challenging dogma: an alternative non-hierarchical, epigenetically regulated model of the urothelium.

Biotechnology and Biological Sciences Research Council to Jennifer Southgate

USD 605,256
2018 - 2021
Project list item
Regulatory networks in basal-like bladder cancer

Fondation ARC pour la Recherche sur le Cancer to Jacqueline Fontugne

 
2017 - 2019
Project list item
Urothelial Stem Cells

National Institute of Diabetes and Digestive and Kidney Diseases to XUE-RU WU, TUNG-TIEN SUN

USD 2,073,748
2017 - 2021
Project list item
Pluripotent stem cell-derived bladder epithelial progenitors for definitive cell replacement therapy of bladder cancer

California Institute for Regenerative Medicine to Philip Beachy

USD 1,400,033
2016 - 2016
Project list item
Analysis of Heparanase for invasion abilities of bladder cancer cells

Japan Society for the Promotion of Science to Yoshihiro Tatsumi

USD 32,892
2016 - 2018
Project list item
Urothelial cancer in the context of normal urothelial differentiation

Swedish Research Council to Mattias Höglund, Håkan Axelson, Fredrik Liedberg, Kristian Pietras

USD 454,630
2016 - 2019
Project list item
Dissecting the Role of APOBEC3 Mutagenic Proteins as Drivers of Genomic Instability and Chemotherapy Resistance in Urothelial Carcinoma

Congressionally Directed Medical Research Programs to Bishoy M Faltas

USD 610,199
2015 - 2016
Project list item
Investigating the cell of origin for bladder cancer

National Cancer Institute to CORY ABATE-SHEN

USD 2,359,626
2015 - 2020
Project list item
Development of novel diagnostic markers for low grade urothelial cancer in urine cytology

Japan Society for the Promotion of Science to Katsuya MATSUDA, Masachika ISEKI, Tatsuhiko KAWASAKI, Masahiro NAKASHIMA

USD 43,742
2015 - 2018
Project list item
Autologous cell engineered bladder augmentation

Medical Research Council to Paolo De Coppi, Martin Birchall, Daniel Wood, Jennifer Southgate, Imran Mushtaq, Massimo Garriboli

USD 555,432
2014 - 2016
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