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Investigating the role of cell cycle plasticity in the growth and progression of bladder cancers

Award Number: R21CA309329
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2028

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Investigating the role of cell cycle plasticity in the growth and progression of bladder cancers - ABSTRACT Cell cycle dysregulation is a fundamental driver of cancer progression, yet our understanding of cell cycle regulation remains largely based on a singular, canonical model. Recent technological advances have revealed that cells can execute distinct cell cycle programs - unique configurations of molecular networks that emerge from genetic and microenvironmental inputs. However, the prevalence and consequence of this cell cycle plasticity in cancer remain poorly understood. This study introduces cell cycle plasticity as a novel conceptual framework to understand bladder cancer heterogeneity. Using innovative single-cell spatial proteomics and machine learning approaches, we will map cell cycle programs across 661 bladder tumors spanning diverse histological and molecular subtypes. We hypothesize that bladder cancer cells execute distinct cell cycle programs that contribute to tumor progression and are shaped by the tumor microenvironment (TME). Through three integrated aims, we will: (1) catalog cell cycle programs driving bladder cancer growth and their association with histological/molecular subtypes, (2) investigate how specific TME configurations influence cell cycles using graph neural networks, and (3) develop experimental models that recapitulate cell cycle programs for mechanistic studies. This work will generate the first systematic catalog of cell cycle heterogeneity in bladder cancer and establish a publicly available resource of single-cell proteomic data mapping cell cycle effectors and TME biomarkers. Beyond advancing our fundamental understanding of bladder cancer biology, this study will provide a foundation for future biomarker discovery and therapeutic targeting strategies aimed at improving patient outcomes through precision oncology.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $412,856 )
2026	2026	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Cancer Biology Research	000	1	4/17/2026	NEW	$412,856
														Subtotal = $412,856

Grand Total All Awards = $412,856

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Investigating the role of cell cycle plasticity in the growth and progression of bladder cancers

Award Number: R21CA309329

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 05/01/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2028

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