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Sex, Chromosomes, and Immunity in Bladder Cancer

Award Number: P01CA278732
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2023
PERIOD OF PERFORMANCE END DATE: 05/31/2028

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Sex, Chromosomes, and Immunity in Bladder Cancer - OVERALL – SUMMARY Bladder cancer (BC) is 3-5 times more common in men even when adjusted for environmental factors such as smoking, the primary risk factor for this disease. The goal of this Program Project Grant (PPG) is to advance our knowledge of “sex as a biological variable (SABV)” in BC, with the ultimate objective of improving patient outcomes by discovering sex-specific drivers that can be targeted therapeutically. Benchmarks of Success and Impact for the Program include identification of key immunological, hormonal, chromosomal, genetic, and epigenetic pathways responsible for sex-driven biological phenotypes in BC to inspire the design of a novel line of BC therapeutics based on each patient’s biological sex. To this end, the PPG will unite three leading laboratories in their respective fields, each tackling the problem of SABV from a unique and complementary standpoint of expertise: immunology, cancer biology/functional genomics, and epigenetics. These three research groups, supported by Cedars-Sinai Medical Center Cancer Center and the Ohio State University Comprehensive Cancer Center, have a proven history of collaboration, with nine joint publications since 2017 and multiple co- authored papers in the pipeline. Project 1 aims to uncover the immunological basis of sex differences in BC, taking advantage of a recent discovery in T cell intrinsic androgen receptor signaling in CD8+ T cell exhaustion. Project 2 will focus on the role of the Y chromosome and the Y-lined epigenetic regulators in driving BC progression and resistance to immune checkpoint blockade (ICB); and Project 3 will investigate tumor suppressing activity of the X chromosome-linked epigenetic regulator and the roles of androgen and estrogen- dependent sex hormone pathways, aiming to elucidate the epigenetic basis of sex differences in BC. All three Projects will be supported by an Administrative Core (Admin Core) and two shared resource Cores – the Systems Pathology Core (Core 1) and the Data Science Core (Core 2). Admin Core will manage and support the entire program by offering administrative and fiscal management support and facilitating communication and scientific interactions. Core 1 will provide state-of-the-art digital pathology services, automated and personalized image analyses, and multiparameter immune monitoring. Core 2 will provide unified data processing, analytical pipelines, data integration, data repository, and statistical consultation. Because male prevalence in cancer incidence and mortality is observed across many other cancer types, our scientific findings will likely have broad implications in cancer medicine far beyond BC.


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: 2025 ( Subtotal = $2,255,521 )
2025	2025	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Cancer Biology Research	000	3	6/27/2025	NON-COMPETING CONTINUATION	$2,255,521
														Subtotal = $2,255,521

Issue Date FY: 2024 ( Subtotal = $2,142,746 )
2024	2024	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Cancer Biology Research	000	2	7/17/2024	NON-COMPETING CONTINUATION	$2,142,746
														Subtotal = $2,142,746

Issue Date FY: 2023 ( Subtotal = $2,272,271 )
2023	2023	CEDARS-SINAI MEDICAL CENTER	8700 BEVERLY BLVD	WEST HOLLYWOOD	CA	90048	LOS ANGELES	USA	Cancer Biology Research	000	1	5/30/2023	NEW	$2,272,271
														Subtotal = $2,272,271

Grand Total All Awards = $6,670,538

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Sex, Chromosomes, and Immunity in Bladder Cancer

Award Number: P01CA278732

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/01/2023

PERIOD OF PERFORMANCE END DATE: 05/31/2028

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