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Engrailed-1 and Epigenetic Vulnerabilities in Metastatic Pancreatic Cancer

Award Number: R37CA249007
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/08/2021
PERIOD OF PERFORMANCE END DATE: 02/28/2026

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Engrailed-1 and Epigenetic Vulnerabilities in Metastatic Pancreatic Cancer - Project Summary/Abstract Pancreatic cancer is the most deadly disease in human malignancies and effective treatment options are limited. Here, we hypothesize that Engrailed-1 (EN1), a neuro-development transcription factor, plays a critical role in pancreatic cancer progression and metastasis via epigenetic mechanism of gene regulation. EN1 is a homeo-domain transcription factor, acting as a transcriptional repressor via recruiting transcriptional repressive complexes. Our preliminary data show that EN1 is highly expressed in metastasis-derived organoids and metastatic lesions of pancreatic cancer mouse model. In addition, EN1 expression is associated with poor prognosis and the squamous molecular subtype of pancreatic cancer. Here, we find that EN1 expression endows aggressive characteristics to pancreatic cancer cells and induces the squamous-PDA identity gene signature. Our data strongly suggest that EN1-mediated epigenetic alterations create a new vulnerability for metastatic pancreatic cancer. Therefore, it is critical to identify the underlying molecular mechanism by which EN1 regulates pancreatic epigenome and contributes to PDA progression and metastasis. To address this, we will employ multi-orthogonal approaches to understand the precise role of EN1 in PDA progression. Here, we propose 1) to determine the role of EN1 in the pancreatic cancer epigenome, and 2) to determine the role of EN1 in pancreatic cancer progression. The proposed study will provide a new insight how EN1-mediated epigenetic alterations impact on aggressive traits of pancreatic cancer. This may open novel avenues for the treatment of pancreatic cancer.


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 = $354,974 )
2025	2025	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Biology Research	001	5	5/22/2025	NON-COMPETING CONTINUATION	$35,497
2025	2025	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Biology Research	000	5	2/12/2025	NON-COMPETING CONTINUATION	$319,477
														Subtotal = $354,974

Issue Date FY: 2024 ( Subtotal = $337,341 )
2024	2024	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Biology Research	000	4	2/8/2024	NON-COMPETING CONTINUATION	$319,585
2024	2024	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Biology Research	001	4	4/16/2024	NON-COMPETING CONTINUATION	$17,756
														Subtotal = $337,341

Issue Date FY: 2023 ( Subtotal = $348,109 )
2023	2023	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Biology Research	000	3	2/24/2023	NON-COMPETING CONTINUATION	$348,109
														Subtotal = $348,109

Issue Date FY: 2022 ( Subtotal = $355,328 )
2022	2022	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Biology Research	001	2	5/3/2022	NON-COMPETING CONTINUATION	$35,533
2022	2022	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Biology Research	000	2	2/21/2022	NON-COMPETING CONTINUATION	$319,795
														Subtotal = $355,328

Issue Date FY: 2021 ( Subtotal = $346,099 )
2021	2021	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Cancer Biology Research	000	1	3/8/2021	NEW	$346,099
														Subtotal = $346,099

Grand Total All Awards = $1,741,851

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Engrailed-1 and Epigenetic Vulnerabilities in Metastatic Pancreatic Cancer

Award Number: R37CA249007

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/08/2021

PERIOD OF PERFORMANCE END DATE: 02/28/2026

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