Monday, June 30, 2025 6/30/2025

Role of LSD1 in Triple Negative Breast Cancer Development and Therapeutic Response

Award Number: R01CA260357
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2023
PERIOD OF PERFORMANCE END DATE: 02/28/2025

Group Awards By:

View Award Description

Role of LSD1 in Triple Negative Breast Cancer Development and Therapeutic Response - PROJECT SUMMARY/ABSTRACT About 10-20% of breast cancers are triple-negative breast cancers (TNBC), which have a poorer prognosis and worse clinical outcome than other types of BC. Due to the lack of target therapies, chemotherapy remains the mainstay of treatment of TNBC, but acquired resistance often develops followed by metastasis and mortality. This supplemental project is closely relevant to the ongoing research proposed in the parent grant R01CA260357 and significantly extends the scope of the current project. Our recent study demonstrated that LSD1 depletion significantly reduced the incidence of BRCA1-deficiency induced mouse mammary gland tumors. Based on this finding, we hypothesize that LSD1 overexpression is essential for breast cancer initiation and development due to BRCA1 loss. In Aim 1, we will validate our preliminary findings and characterize the functional role of LSD1 in BRCA1 mutation mediated TNBC progression. We will also investigate if LSD1 overexpression contributes to PARPi resistance. Furthermore, we will explore the in vivo roles of LSD1 in tumor progression using xenograft and mammary gland BRCA1 deficient TNBC mouse models. Cumulative evidence has suggested that epigenetic silencing of a subset of cytotoxic T-cell lymphocyte (CTL) attracting chemokines (e.g. Th1-type CXCL9 and CXCL10) plays an important role in shaping the tumor-promoting immune environment. However, the exact epigenetic mechanisms underlying chemokine silencing are still unclear. Our recent studies showed that LSD1- mediated silencing of CTL chemokines is associated with H3K4 demethylation at proximal promoter regions. Tissue Factor Pathway Inhibitor 2 (TFPI2), a tumor suppressor gene, was identified as a key LSD1 targeted gene. Induction of TFPI2 by LSD1 inhibition downregulates activity of matrix metalloproteinases (MMPs) and promotes stability of chemokines, leading to enhanced CD8+ T-cell infiltration in tumors. Based on these new findings, we hypothesize that overexpression of LSD1 facilities TNBC progression through promoting immune suppressive environment. In Aim 2, we will characterize the crosstalk between epigenetic changes and TNBC immune environment and further elucidate the molecular basis of LSD1-medicated chemokine silencing in promoting TNBC progression. The proposed studies are expected to provide key preclinical data, novel mechanistic insight, and rationales to address mechanistic and clinical associations between epigenetic defects and TNBC tumor environment and tackles a significant clinical problem. Thus, this project has high scientific significance and clinical relevance.


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 = $345,700 )
2025	2025	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cancer Treatment Research	002	6	2/12/2025	NON-COMPETING CONTINUATION	$311,131
2025	2025	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cancer Treatment Research	004	6	5/22/2025	NON-COMPETING CONTINUATION	$34,569
2025	2025	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cancer Treatment Research	003	6	5/1/2025	NON-COMPETING CONTINUATION	$0
2025	2024	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cancer Treatment Research	005	5	6/16/2025	SUPPLEMENT FOR EXPANSION	$0
2025	2023	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cancer Treatment Research	001	4	1/17/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$110,454
2025	2022	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Cancer Treatment Research	000	2	1/17/2025	NON-COMPETING CONTINUATION	-$110,454
														Subtotal = $345,700

Issue Date FY: 2024 ( Subtotal = $352,726 )
2024	2024	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cancer Treatment Research	003	5	4/17/2024	NON-COMPETING CONTINUATION	$17,479
2024	2024	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cancer Treatment Research	004	5	9/3/2024	SUPPLEMENT FOR EXPANSION	$40,735
2024	2024	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cancer Treatment Research	002	5	2/7/2024	NON-COMPETING CONTINUATION	$314,645
2024	2023	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Cancer Treatment Research	000	3	10/31/2023	NON-COMPETING CONTINUATION	-$368,725
2024	2023	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cancer Treatment Research	001	4	10/31/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$348,592
														Subtotal = $352,726

Issue Date FY: 2023 ( Subtotal = $368,725 )
2023	2023	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Cancer Treatment Research	000	3	2/25/2023	NON-COMPETING CONTINUATION	$368,725
														Subtotal = $368,725

Issue Date FY: 2022 ( Subtotal = $366,683 )
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Cancer Treatment Research	001	2	5/11/2022	NON-COMPETING CONTINUATION	$29,934
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Cancer Treatment Research	000	2	2/3/2022	NON-COMPETING CONTINUATION	$336,749
														Subtotal = $366,683

Issue Date FY: 2021 ( Subtotal = $357,994 )
2021	2021	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Cancer Treatment Research	000	1	2/16/2021	NEW	$357,994
														Subtotal = $357,994

Grand Total All Awards = $1,791,828

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Role of LSD1 in Triple Negative Breast Cancer Development and Therapeutic Response

Award Number: R01CA260357

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/15/2023

PERIOD OF PERFORMANCE END DATE: 02/28/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer