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Project

Modeling bladder cancer pathogenesis and tumor evolution

Funder: National Cancer Institute

Funding period
USD 3.4 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.

 
162
Projects
USD 103.9 M
Aggregated funding amount
USD 831 K
Average funding amount
Project list item
Dissecting myeloid cell-mediated resistance to immune checkpoint blockade in bladder cancer

National Cancer Institute to NINA BHARDWAJ, MATTHEW GALSKY, JUN ZHU

USD 703,400
2020 - 2025
Project list item
CD40 agonism for the treatment of bladder cancer

National Cancer Institute to CHRISTOPHER STUART GARRIS

USD 64,554
2020 - 2023
Project list item
A new bladder cancer model based on tissue reprogramming and gene targeting

National Cancer Institute to FLAMINIA TALOS, DAIFENG WANG

USD 203,843
2020 - 2021
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
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, Eugenio Zoni, Vera Genitsch, Martina Minoli, Marianna Kruithof-de Julio, Franziska Singer, Federico La Manna, Kiu Yan Charlotte Ng

USD 709,398
2019 - 2023
Project list item
[Efficacy and toxicity of bladder instillation of anti-tumor peptide for inhibition of bladder tumor in mice] - Original in Japanese

Japan Society for the Promotion of Science to Toru SHIMAZUI, Takahiro KOJIMA, Hiroyuki NISHIYAMA, Kazuhiro YOSHIKAWA

USD 39,492
2019 - 2022
Project list item
Combatting Bladder Cancer by Inducing Epithelial Turnover

National Cancer Institute to SOMAN N ABRAHAM

USD 372,404
2019 - 2021
Project list item
Chromatin Modifier Gene Mutation and Enhancer Dysfunction in Bladder Cancer

National Cancer Institute to BYRON H LEE

USD 486,410
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 821,670
2019 - 2024
Project list item
Clonal evolution and molecular stratification of urothelial carcinoma in situ of the urinary bladder

German Research Foundation to Nadine Gaisa, Stefan Garczyk

 
2019 -
Project list item
The role of a new molecular driver in bladder cancer

National Cancer Institute to DALEY MORERA

USD 90,032
2018 - 2021
Project list item
A co-clinical trial of chemotherapy response in bladder cancer using patient-derived tumor organoids

V Foundation for Cancer Research to Michael M Shen

USD 600,000
2018 - 2021
Project list item
Elucidating immunotherapy resistance mechanisms in non-T cell-inflamed bladder cancer

National Cancer Institute to RANDY F. SWEIS

USD 425,338
2018 - 2022
Project list item
Novel recombinant BCG for immunotherapy of bladder cancer

National Cancer Institute to BORIS SHOR

USD 290,014
2018 - 2020
Project list item
SPORE in Bladder Cancer

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

USD 4,438,686
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
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