Thursday, July 3, 2025 7/3/2025

Epigenetic regulation of intestinal tuft cells

Award Number: R01DK137771
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: 08/01/2024
PERIOD OF PERFORMANCE END DATE: 06/30/2028

Group Awards By:

View Award Description

Epigenetic regulation of intestinal tuft cells - Intestinal epithelial cells reside at the direct interface between the microbiota and mammalian host, and are thus uniquely poised to sense microbial signals that calibrate intestinal immunity and function. Tuft cells are a specialized epithelial cell that have recently been shown to respond to microbial stimuli and initiate and amplify type 2 immune responses in the intestine. However, despite a clear relationship between the microbiota and intestinal health, the mechanisms underlying how the microbiota instruct tuft cell homeostasis and function remain poorly understood. Epigenetics represent a central mechanism that can potentially link microbial triggers in the pathogenesis of intestinal disease. Consistent with this concept, we previously identified that epithelial loss of an epigenetic-modifying enzyme disrupted microbiota-sensitive intestinal homeostasis and increased susceptibility to intestinal damage. Our new preliminary data suggest that regulation of tuft cell development and homeostasis may be epigenetically regulated and dynamically controlled by distinct metabolites produced by the intestinal microbiota. Based on these findings, we hypothesize that (1) tuft cell responses in the intestine may be calibrated by distinct components of the microbiota through an epigenetic sensor and that (2) epigenetic mechanisms in stem cells may regulate tuft cell development and function. To investigate these hypotheses, we will (i) interrogate how distinct commensal bacterial-derived metabolites instruct intestinal stem cell differentiation to tuft cells through an epigenetic-modifying enzyme, and (ii) directly identify and investigate new mechanisms by which the stem cell epigenetic landscape can be modulated to control tuft cell differentiation in the intestine. This work will uncover novel epigenetically-regulated pathways that direct tuft cell biology in the intestine, and therefore guide personalized approaches for treating intestinal diseases.


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 = $627,541 )
2025	2025	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	6/18/2025	NON-COMPETING CONTINUATION	$627,541
														Subtotal = $627,541

Issue Date FY: 2024 ( Subtotal = $627,541 )
2024	2024	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	7/23/2024	NEW	$627,541
														Subtotal = $627,541

Grand Total All Awards = $1,255,082

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Epigenetic regulation of intestinal tuft cells

Award Number: R01DK137771

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: 08/01/2024

PERIOD OF PERFORMANCE END DATE: 06/30/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer