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Investigating the relationship between the systemic response to infection and tumor initiation and progression in Brca1 breast cancer

Award Number: F30CA281082
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 06/01/2023
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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Investigating the relationship between the systemic response to infection and tumor initiation and progression in Brca1 breast cancer - Abstract Breast cancer (BC) is one of the most common solid tumors in women world-wide. Loss-of-function mutations in the DNA repair gene, BRCA1, is among the most clinically relevant factors that increases BC incidence. Despite such a strong link with BC, not every woman with a BRCA1 mutation will develop BC. Therefore, identification of cooperating risk factors, such as life history events, that initiate tumor development will enable development of biomarkers for early detection, prevention and potentially targeted treatments. The dos Santos lab has found that whole body changes resulting from urinary tract infection (UTI) remodel the transcriptome of mammary epithelial cells (MECs) and the tissue microenvironment. Therefore, we hypothesize that UTI is a life history event that promotes BC incidence. Specifically, I hypothesize that UTI induces alterations to MECs and modifies mammary stromal and immune cells in such a way that tumors in Brca1 knockout mice will develop faster. I have evaluated changes to mammary tissue with single cell RNA-sequencing and will further investigate these findings through the proposed aims using multi-color flow cytometry, histopathology, transplantation experiments and organoid studies. Overall, the significance of this proposed research is to: i) better understand mechanisms of tumor initiation and early progression in Brca1-BC, ii) identify immune-suppressive cellular changes in mammary tissue resulting from UTI, and iii) provide justification for UTI as a novel BC risk factor in patients with BRCA1 mutations. The outcome of these approaches will provide a deeper mechanistic understanding of how a specific life history event modulates the responsiveness of MECs to cancer promoting signals. Additionally, this proposal will provide a novel appreciation of the role of Brca1, and the effects of systemic signals produced after infection, in modifying mammary stromal and immune cell function.


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 = $54,538 )
2025	2025	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Research Manpower	003	3	5/26/2025	NON-COMPETING CONTINUATION	$564
2025	2025	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Research Manpower	002	3	5/13/2025	NON-COMPETING CONTINUATION	$53,974
2025	2024	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Research Manpower	000	2	10/30/2024	NON-COMPETING CONTINUATION	$0
2025	2024	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Research Manpower	001	2	3/12/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $54,538

Issue Date FY: 2024 ( Subtotal = $41,277 )
2024	2024	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Research Manpower	000	2	5/23/2024	NON-COMPETING CONTINUATION	$41,277
														Subtotal = $41,277

Issue Date FY: 2023 ( Subtotal = $39,997 )
2023	2023	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Research Manpower	001	1	5/10/2023	NEW	$0
2023	2023	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Research Manpower	000	1	5/10/2023	NEW	$39,997
														Subtotal = $39,997

Grand Total All Awards = $135,812

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Investigating the relationship between the systemic response to infection and tumor initiation and progression in Brca1 breast cancer

Award Number: F30CA281082

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 06/01/2023

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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