Wednesday, February 18, 2026 2/18/2026

Investigating the function of subclonal cooperation in breast cancer progression

Award Number: F31CA265248
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 12/01/2021
PERIOD OF PERFORMANCE END DATE: 12/31/2024

Group Awards By:

View Award Description

Investigating the function of subclonal cooperation in breast cancer progression - Project Summary/Abstract Intratumor genetic heterogeneity is present in a vast majority of solid cancers and correlates with tumor aggressiveness and poor therapeutic response. Whether tumor heterogeneity promotes tumor growth and survival, and the potential mechanisms driving these phenotypic changes, are open areas of investigation. To explore this fundamental gap in knowledge, I generated a model for studying subclonal cooperation and tumor heterogeneity in vitro and in vivo, respectively, using isogenic MCF10A cell lines that either overexpress MYC (MYC) or oncogenic HRASG12V (HRAS). MYC and oncogenic RAS are two canonical oncogenes that are known to signal in distinct pathways, though studies focused on MYC and HRAS interactions have primarily explored cell intrinsic mechanisms of cooperation. Therefore, I will use MYC and HRAS as an exemplar for subclonal cooperation to study their cooperativity in distinct cell populations. In preliminary studies using the MYC and HRAS model, I made the exciting observation that individual subclones expressing MYC or HRAS cooperate non-cell autonomously: cell proliferation increases when subclones are grown together in vitro and tumor growth is more rapid when subclones are co-injected into mice. Importantly, these data suggest targeting clonal interdependence may be necessary to improve therapeutic strategies. We hypothesize tumor subclones cooperate to elicit emergent tumor properties promoting tumor growth, and, potentially, tumor metastasis and drug resistance. The three Experimental Aims of this proposed research will rigorously test my hypothesis, studying the phenomenon of subclonal cooperation in cell culture and in orthotopic and patient derived xenograft (PDX) models. Experimental Aim 1 will test if subclonal cooperation is necessary for more rapid tumor initiation and proliferation, by deconstructing heterogenous tumors at distinct timepoints during tumor progression. Experimental Aim 2 will explore how tumor heterogeneity is functional by defining how exosome mediated protein transfer contributes to subclonal cooperation. Finally, in Experimental Aim 3, I will test whether subclonal interactions promote therapeutic resistance in orthotopic mouse mammary tumors generated using human- derived cell lines. Additionally, I will validate our findings of subclonal heterogeneity by characterizing the subclonal expression of specific oncogenes present in in a library of readily available PDX models. Together, these data will improve our understanding of subclonal cooperation in tumor progression, providing key insights for future work aimed at efficiently deconstructing and treating complex, heterogenous tumors.


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 = -$4,732 )
2026	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Research Manpower	000	3	1/27/2026	NON-COMPETING CONTINUATION	-$4,732
														Subtotal = -$4,732

Issue Date FY: 2025 ( Subtotal = -$4,021 )
2025	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Research Manpower	000	3	1/24/2025	NON-COMPETING CONTINUATION	-$4,021
														Subtotal = -$4,021

Issue Date FY: 2024 ( Subtotal = $40,673 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Cancer Research Manpower	001	3	5/7/2024	NON-COMPETING CONTINUATION	$1,280
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Research Manpower	000	3	1/26/2024	NON-COMPETING CONTINUATION	$39,393
														Subtotal = $40,673

Issue Date FY: 2023 ( Subtotal = $39,393 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Research Manpower	000	2	2/16/2023	NON-COMPETING CONTINUATION	$39,393
														Subtotal = $39,393

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Research Manpower	000	1	3/10/2022	NEW	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $37,735 )
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Research Manpower	001	1	7/26/2021	NEW	$0
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cancer Research Manpower	000	1	7/26/2021	NEW	$37,735
														Subtotal = $37,735

Grand Total All Awards = $109,048

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Investigating the function of subclonal cooperation in breast cancer progression

Award Number: F31CA265248

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 12/01/2021

PERIOD OF PERFORMANCE END DATE: 12/31/2024

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer