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Pfn1’s Role in Genomic Stability and Immune Response in Breast Cancer

Award Number: F31CA306130
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/01/2025
PERIOD OF PERFORMANCE END DATE: 08/31/2027

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Pfn1’s Role in Genomic Stability and Immune Response in Breast Cancer - Project Summary Breast cancer is the second leading cause of cancer related deaths in women in the United States Immune checkpoint blockade immunotherapy is an emerging treatment for breast cancer, particularly for triple-negative breast cancer which lacks targeted therapies. Immune checkpoint blockade failure is often due to immune- excluded tumor microenvironments, specifically the absence of CD8+ T cell infiltration. Currently immune checkpoint blockade agents are used in combination with conventional chemotherapies which enhance the function of immunotherapy by inducing DNA damage a trigger for an anti-tumor immunological response. However, tumors are known to become resistant to chemotherapies, therefore identification of novel mechanisms to induce DNA damage and thus CD8+ T cell infiltration is key for improving immune checkpoint blockade immunotherapy success. Profilin-1 (Pfn1) is an actin-binding protein that has been reported to have context dependent tumor intrinsic roles in breast cancer. While overexpression of Pfn1 has been shown to suppress tumorigenesis, knockdown of Pfn1 has been demonstrated to limit metastatic outgrowth. However, the impact of Pfn1 modulation on the tumor immune microenvironment in breast cancer remains uninvestigated. My preliminary data suggests genetic disruption of the Pfn1 gene leads to an increase in CD8+ T cell infiltration and significant tumor regression. The goal of this project is to investigate whether and how loss of Pfn1 causes a pro-inflammatory, anti-tumor microenvironment thereby increasing immunotherapy efficacy. The proposed research will be complemented by a training plan I designed to achieve the aims of this project and prepare myself for the next phase of my research career. My undergraduate and early graduate school research focused on molecular mechanisms of cancer cell migration and tumor biology. During the F31 fellowship period I will extend my understanding of cancer to the tumor immune microenvironment and immunotherapy treatment. I will learn technical skills including how to perform flow cytometry analysis, immunotherapy administration, and microfluidic device fabrication. I will build upon my skills in the design of rigorous scientific approaches, mentorship, and outreach.


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 = $50,114 )
2026	2026	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Cancer Research Manpower	000	2	8/12/2026	NON-COMPETING CONTINUATION	$50,114
														Subtotal = $50,114

Issue Date FY: 2025 ( Subtotal = $49,538 )
2025	2025	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Cancer Research Manpower	001	1	7/16/2025	NEW	$0
2025	2025	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Cancer Research Manpower	000	1	7/16/2025	NEW	$49,538
														Subtotal = $49,538

Grand Total All Awards = $99,652

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Pfn1’s Role in Genomic Stability and Immune Response in Breast Cancer

Award Number: F31CA306130

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/01/2025

PERIOD OF PERFORMANCE END DATE: 08/31/2027

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