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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.

 
44
Projects
USD 34.2 M
Aggregated funding amount
USD 877 K
Average funding amount
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
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
SPORE in Bladder Cancer

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

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
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

USD 639,521
2018 - 2022
Project list item
The Role of EZH2 in Non-Muscle Invasive Bladder Cancer

United States Department of Veterans Affairs to JOSHUA JAMES MEEKS

 
2016 - 2020
Project list item
Regulation of ATDC by TP63 and its role in bladder cancer

National Cancer Institute to PHILLIP L PALMBOS

USD 524,880
2016 - 2021
Project list item
Notch in bladder cancer: oncogene and tumour suppressor

Canadian Cancer Society to Peter Black, Colin Collins, Mads Daugaard, Yuzhuo Wang

USD 758,595
2016 - 2020
Project list item
Determinants of T-Cell Activity in Bladder Cancer

Congressionally Directed Medical Research Programs to Vivek K Arora

USD 549,000
2015 - 2016
Project list item
Synergistic Immuno-Photo-Nanotherapy for Bladder Cancer

Congressionally Directed Medical Research Programs to Brant A. Inman

USD 624,398
2015 - 2016
Project list item
The Role of TP63 and ATDC in Invasive Bladder Cancers

Bladder Cancer Advocacy Network to Phillip Palmbos, Diane Simeone, Mats Ljungman, Stephanie Daignault

USD 100,000
2015 - 2017
Project list item
Epigenetic regulation of bladder cancer progression

Bladder Cancer Advocacy Network to Cory Abate-Shen, Michael M Shen, David Brian Solit, James M. McKiernan, Cathy Mendelsohn, Hikmat Al-Ahmadie

USD 300,000
2015 - 2017
Project list item
Investigating the cell of origin for bladder cancer

National Cancer Institute to CORY ABATE-SHEN

USD 1,899,096
2015 - 2020
Project list item
Biology and Therapy of Basal Bladder Cancers

Cancer Prevention and Research Institute of Texas to Colin Dinney

USD 865,587
2014 -
Project list item
Consequences of ARID1A Inactivation in Bladder Cancer

Bladder Cancer Advocacy Network to RYOICHI SAITO, William Y. Kim

USD 100,000
2014 - 2016
Project list item
Oncogenic Function of ATDC in Bladder Cancer

National Cancer Institute to DIANE M SIMEONE

USD 2,306,274
2014 - 2019
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