Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Dissecting roles of Lunatic Fringe-dependent Notch signaling in pancreatic cancer

Award Number: R01CA276347
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2024
PERIOD OF PERFORMANCE END DATE: 04/30/2029

Group Awards By:

View Award Description

Dissecting roles of Lunatic Fringe-dependent Notch signaling in pancreatic cancer - Despite improvements in overall survival for most cancers, survival for patients with pancreatic cancer remains dismally low due to the late diagnosis and rapid spreading. Understanding pancreatic cancer initiation and progression is of great importance for the development of effective intervention strategy. Mouse models recapitulating human pancreatic ductal adenocarcinoma (PDAC) have been generated through activation of oncogenic Kras combined with various genetic mutations in different pancreatic cell types, and studies using mouse genetics suggest that both acinar and ductal cells can give rise to PDAC, and cellular origins and specific gene mutations may determine the precursor lesion initiation, progression, as well as molecular subtype of PDAC. Notch signaling pathway is a master regulator of cell fate decision and differentiation critical for pancreatic development and is dysregulated in pancreatic cancer. We recently discovered that expression of a Notch modulator, Lunatic Fringe (Lfng), is confined to a subset of centroacinar cells in the normal pancreas. Lfng-expressing centroacinar cells are uniquely susceptible to oncogenic transformation and deletion of Lfng blocks tumor initiation from these cells. Lfng is upregulated in acinar and ductal cell-derived precursor lesions, and deletion of Lfng decelerates tumor development from these two cell types. Thus, Lfng exerts oncogenic roles in the development of PDAC from three distinct cellular origins: centroacinar, acinar and ductal cells. Amplification and upregulation of LFNG are noted in human PDAC and are associated with poor survival. Therefore, we propose to dissect roles of Lfng-dependent Notch signaling in pancreatic cancer using multiple approaches including organoid culture, lineage tracing, temporal and lineage-specific genetic manipulations, differential gene expression analysis, as well as functional analysis of candidate genes in human PDAC cell lines to address the following Specific Aims: 1) determine roles of Lfng-dependent Notch signaling in pancreatic cancer development from Lfng- expressing centroacinar cells; 2) determine roles of Lfng-dependent Notch signaling in acinar- and ductal-derived PDAC pathogenesis; and 3) characterize Lfng-expressing pancreatic cancer cells and identify genes differentially expressed in these cells as potential therapeutic targets. We hope to demonstrate that Lfng is critical for the initiation and progression of pancreatic cancers arising from different cell types of the pancreas, and that Lfng marks pancreatic cancer stem cells thought to be responsible for drug resistance and cancer relapse. Identification of genes downstream of Lfng-dependent Notch signaling may lead to the development of biomarkers for targeted therapy for this particularly deadly disease.


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 = $354,563 )
2026	2026	UNIVERSITY OF MISSISSIPPI MEDICAL CENTER	2500 N STATE ST	JACKSON	MS	39216	HINDS	USA	Cancer Biology Research	000	3	5/5/2026	NON-COMPETING CONTINUATION	$354,563
														Subtotal = $354,563

Issue Date FY: 2025 ( Subtotal = $354,563 )
2025	2025	UNIVERSITY OF MISSISSIPPI MEDICAL CENTER	2500 N STATE ST	JACKSON	MS	39216	HINDS	USA	Cancer Biology Research	000	2	4/11/2025	NON-COMPETING CONTINUATION	$319,106
2025	2025	UNIVERSITY OF MISSISSIPPI MEDICAL CENTER	2500 N STATE ST	JACKSON	MS	39216	HINDS	USA	Cancer Biology Research	001	2	6/6/2025	NON-COMPETING CONTINUATION	$35,457
														Subtotal = $354,563

Issue Date FY: 2024 ( Subtotal = $354,563 )
2024	2024	UNIVERSITY OF MISSISSIPPI MEDICAL CENTER	2500 N STATE ST	JACKSON	MS	39216	HINDS	USA	Cancer Biology Research	000	1	4/16/2024	NEW	$354,563
														Subtotal = $354,563

Grand Total All Awards = $1,063,689

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Dissecting roles of Lunatic Fringe-dependent Notch signaling in pancreatic cancer

Award Number: R01CA276347

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2024

PERIOD OF PERFORMANCE END DATE: 04/30/2029

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer