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Role of trefoil factor family proteins in beta cell function.

Award Number: R01DK134652
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/20/2023
PERIOD OF PERFORMANCE END DATE: 11/30/2026

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Role of trefoil factor family proteins in beta cell function. - Modified Project Summary/Abstract Section In the United States, nearly 10% of the population (more than 30 million) has type 2 diabetes (T2D) and this number is growing not only in older adults but also in children, teens, and young adults. The alarming and continued increase of T2D incidence, especially among young Americans, creates an urgent need for new therapeutics and interventions. One of the underlying conditions leading to T2D is the dysfunction of beta cells. While discovering the molecular changes in beta cells leading to their dysfunction has been a focused effort in the field, less is known about how the microenvironment, such as secreted factors from exocrine pancreas, may also contribute to pathogenesis. Trefoil factor family peptides (TFF1, TFF2, and TFF3) are unique secreted proteins in that they contain six cysteine residues that form three intramolecular disulfide bridges, which makes them more stable and resistant to proteases and other harsh conditions. Trefoil factors have been shown to play essential roles in maintaining the integrity of gut and lung epithelium, and in repairing epithelial cells after injury. Trefoil factors are expressed in the pancreas, but their roles are not well understood. We have preliminary data revealing that Tff2 is expressed by the exocrine pancreas and the knockout of this gene in the pancreas leads to beta cell dysfunction in adult mice. However, the molecular and cellular mechanisms by which Tff2 exerts on beta cells are unknown. Our central hypothesis is that Tff2 protects against the damaging effects of diabetogenic stress. We will use our pancreas-specific knockout mouse model of Tff2 and primary human tissues/cells for our studies. In Aim 1, we will examine how the lack of Tff2 in the murine pancreas affects beta cell dysfunction in aged mice and under diabetogenic conditions. In Aim 2, we will clarify the distribution patterns of trefoil factor family proteins and their receptors in human pancreatic tissues and study the crosstalk between exocrine and islet cells via TFF2 by using in vitro model systems. We will use innovative tools to test novel hypotheses on the actions about trefoil factors within a translation-focused institutional environment at City of Hope. This work will positively impact diabetes research by addressing a promising candidate secretory factor for diabetes prevention/treatment.


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 = $568,098 )
2026	2026	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	12/5/2025	NON-COMPETING CONTINUATION	$568,098
														Subtotal = $568,098

Issue Date FY: 2025 ( Subtotal = $568,098 )
2025	2025	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	7/16/2025	NON-COMPETING CONTINUATION	$56,809
2025	2025	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	11/13/2024	NON-COMPETING CONTINUATION	$511,289
														Subtotal = $568,098

Issue Date FY: 2024 ( Subtotal = $545,375 )
2024	2024	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	11/9/2023	NON-COMPETING CONTINUATION	$511,289
2024	2024	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	5/8/2024	NON-COMPETING CONTINUATION	$34,086
														Subtotal = $545,375

Issue Date FY: 2023 ( Subtotal = $565,036 )
2023	2023	BECKMAN RESEARCH INSTITUTE OF THE CITY OF HOPE	1500 DUARTE RD	DUARTE	CA	91010	LOS ANGELES	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	1/19/2023	NEW	$565,036
														Subtotal = $565,036

Grand Total All Awards = $2,246,607

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Role of trefoil factor family proteins in beta cell function.

Award Number: R01DK134652

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/20/2023

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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