# Modeling bladder cancer pathogenesis and tumor evolution

> **NIH NIH P01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $1,718,998

## 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
Pro...

## Key facts

- **NIH application ID:** 9972885
- **Project number:** 5P01CA221757-03
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Cory Abate-Shen
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,718,998
- **Award type:** 5
- **Project period:** 2018-09-11 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9972885

## Citation

> US National Institutes of Health, RePORTER application 9972885, Modeling bladder cancer pathogenesis and tumor evolution (5P01CA221757-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9972885. Licensed CC0.

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