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Project

Modeling bladder cancer pathogenesis and tumor evolution

Funder: National Cancer Institute

Funding period
USD 1.8 M
Funding amount
Abstract
Project Summary/Abstract: This new Program Project will investigate the molecular mechanisms underlying the pathogenesis of bladder cancer. Our objectives are: (i) to study clonal evolution from non-muscle invasive to invasive to metastatic disease, and to elucidate molecular drivers for each stage of evolution; (ii) to study mechanisms of disease pathogenesis, with a major focus on the functional role of mutations that affect the epigenome; (iii) to elucidate mechanisms of disease response and resistance, with a major focus on understanding those that affect response to chemotherapy; and (iv) to generate novel human patient-derived and genetically-engineered mouse models (GEMMs) to study disease pathogenesis and to pursue co-clinical investigations. To achieve these objectives, we have assembled a highly accomplished multi-disciplinary team at Columbia University Medical Center (Cory Abate-Shen, Michael Shen, James McKiernan, Tian Zheng) and Memorial Sloan Kettering Cancer Center (David B. Solit, Hikmat Al-Ahmadie, Barry Taylor) with complementary expertise in genomic analyses (DBS, HA, BT), molecular investigations (CAS, MS, DBS), treatment response (CAS, MS, DBS, JM, BT), biostatistics and bioinformatics (TZ, BT), molecular pathology (HAA), generation of human and mouse cancer models (CAS, MS), co-clinical and clinical investigations (DBS, JM, CAS, JM, MS). We will pursue three interrelated Projects that are supported by three Cores. Project 1, led by David Solit, will seek to define the biologic functions of the histone demethylase, KDM6A, in bladder cancer pathogenesis, as well as the temporal occurrence of mutations in this gene during tumor progression. Project 2, led by Cory Abate-Shen, will analyze the functions of the chromatin remodeling gene, ARID1A, in muscle- invasive bladder cancer, focusing on its role in disease pathogenesis, its effect on treatment response and its molecular mechanisms of action. Project 3, led by Michael Shen, will investigate tumor evolution and drug response in human patient-derived bladder cancer organoids, focusing on genetic determinants of genomic instability, alterations of the epigenome, and the role of heterogeneity in drug sensitivity and resistance. The Molecular Pathology Core (Core A), led by Hikmat Al-Ahmadie, will maintain a biorepository of urothelial cancer tumors, including the tissues used for organoid generation, and will provide histopathological analyses for all three projects. The Bladder Cancer Models Core (Core B), led by Michael Shen will serve as a central hub for the generation and analysis of cancer models for all three projects, including human patient-derived organoid and xenograft models, and GEMMs. The Administrative Core (Core C), led by Cory Abate-Shen, will provide support for bioinformatic and biostatistical analyses and organizational support for Program Project investigators, and will coordinate with the Internal and External Advisory Boards. In summary, this Program Project is led by a highly collaborative team of investigators with diverse but complementary expertise who have substantial track records in cancer research, and are located in close proximity in New York City.

 
232
Projects
USD 177.0 M
Aggregated funding amount
USD 859 K
Average funding amount
Project list item
Investigating underlying molecular mechanisms of epigenetic therapies in muscle-invasive bladder cancer

Bladder Cancer Advocacy Network to Swathi Ramakrishnan

USD 1,700
2019 - 2019
Project list item
Refined phenotyping and personalized targeting of muscle-invasive bladder cancer

Swiss National Science Foundation to Roland Seiler, Vera Genitsch, Franziska Singer, Kiu Yan Charlotte Ng, Marianna Kruithof-de Julio

USD 597,404
2019 - 2023
Project list item
Combatting Bladder Cancer by Inducing Epithelial Turnover

National Cancer Institute to SOMAN N ABRAHAM

USD 203,510
2019 - 2021
Project list item
Chromatin Modifier Gene Mutation and Enhancer Dysfunction in Bladder Cancer

National Cancer Institute to BYRON H LEE

USD 243,205
2019 - 2024
Project list item
Phase 1/2 Study of Modern Immunotherapy in BCG-Relapsing Urothelial Carcinoma of the Bladder - (ADAPT-BLADDER)

National Cancer Institute to NOAH M HAHN

USD 656,816
2019 - 2024
Project list item
Defining the impact of intra-tumoral morphologic, immune and mutational heterogeneity in urothelial carcinoma

National Cancer Institute to HIKMAT AL-AHMADIE

USD 410,835
2019 - 2024
Project list item
The role of a new molecular driver in bladder cancer

National Cancer Institute to DALEY MORERA

USD 45,016
2018 - 2021
Project list item
Elucidating immunotherapy resistance mechanisms in non-T cell-inflamed bladder cancer

National Cancer Institute to RANDY F. SWEIS

USD 212,669
2018 - 2022
Project list item
Novel recombinant BCG for immunotherapy of bladder cancer

National Cancer Institute to BORIS SHOR

USD 290,014
2018 - 2019
Project list item
SPORE in Bladder Cancer

National Cancer Institute to DEAN F. BAJORIN, TIMOTHY AN-THY CHAN, IRINA OSTROVNAYA, HIKMAT AL-AHMADIE, MICHAEL STEPHEN GLICKMAN, DAVID B SOLIT

USD 2,299,837
2018 - 2023
Project list item
Modeling bladder cancer metastasis using human patient-derived tumor organoids

Bladder Cancer Advocacy Network to Michael M Shen

USD 300,000
2018 - 2020
Project list item
Circulating tumor DNA as a predictive biomarker in metastatic bladder cancer

Canadian Institutes of Health Research to Gillian Rae Vandekerkhove, Alexander William Wyatt

USD 53,221
2018 - 2021
Project list item
Role of B-arrestins in bladder cancer progression and response to chemotherapy

United States Department of Veterans Affairs to BAL L LOKESHWAR

 
2018 - 2022
Project list item
Deciphering the neoantigen landscape in bladder cancer patients

Swiss National Science Foundation to Laurent Derré, Sylvain Nguyen, Alexandre Harari

USD 639,521
2018 - 2022
Project list item
Ty21a immunotherapy of non-muscle-invasive bladder cancer

Swiss National Science Foundation to Denise Nardelli Haefliger, Mathieu Chevalier, Patrice Jichlinski, Lenka Chalupova

USD 436,670
2018 - 2021
Project list item
Non invasive Cell Based Liquid Biopsy Platform for Bladder Cancer

European Commission

USD 4,291,985
2017 - 2020
Project list item
Circulating tumour DNA as a precision oncology tool for metastatic bladder cancer

Canadian Institutes of Health Research to Alexander William Wyatt

USD 98,846
2017 - 2020
Project list item
In silico analysis of early stage urothelial carcinoma to identify markers of invasion

Canadian Institutes of Health Research to Chelsea Jackson

USD 769
2017 - 2018
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