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

Defining mechanisms of epithelial surveillance by intestinal T cells

Award Number: R01DK113375
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: 07/01/2017
PERIOD OF PERFORMANCE END DATE: 06/30/2030

Group Awards By:

View Award Description

Defining mechanisms of epithelial surveillance by intestinal T cells - Colorectal cancer (CRC) remains a major cause of cancer-related mortality, and its incidence is increasing in younger adults. Immunotherapies have shown limited success in patients with microsatellite stable (MSS) CRC, underscoring the urgent need to define the mechanisms of early immune surveillance at mucosal sites. The intestinal epithelium is uniquely positioned at the interface of microbial, dietary, and host signals, and its crosstalk with resident and recruited lymphocytes is likely critical in shaping tumor initiation and progression. Work from the current funding cycle has demonstrated that intraepithelial γδ T cells possess distinct, stage-specific roles in CRC, with cytotoxic Vγ7⁺ and Vγ1⁺ cells enriched in early lesions and IL-17–producing Vγ6⁺ cells dominating established tumors. We also identified a microbiota-dependent role for IgA in suppressing epithelial cell proliferation and tumorigenesis. Building on this work, the Mucida and Beyaz labs generated compelling preliminary data using complementary models and tools from both labs. The Mucida lab used a fate-mapping approach labelling naïve cells (iSelltomato mice) to characterize T cells recently recruited to the tissue and implemented orthotopic implantation of genetically defined tumor organoids, revealing that early CD4⁺ T cell recruitment, clonal expansion, and cytokine production are predictive of tumor restraint. Additionally, the Mucida lab developed a novel fate-mapping approach (TRACK mice) to fate-map recently activated T cells, which will allow the labelling of T cells recently activated by the transformed epithelium, permitting the characterization of early T cell responses in secondary or organized lymphoid tissues. In parallel, the Beyaz lab demonstrated that colonization with specific Helicobacter species enhances epithelial MHC-II expression through YAP signaling, promotes T cell infiltration, and limits CRC progression; epithelial MHC-II is both necessary and sufficient for this effect. Together, these findings support a model in which microbial modulation of epithelial immunogenicity dictates the quality of early T cell responses. In this renewal, we will define how microbial cues regulate epithelial gene expression and antigen presentation through transcriptomic and chromatin profiling of IECs, including MHC-II and YAP-dependent pathways (Aim 1); use TRACK fate-mapping strategies, single-cell RNA/TCR sequencing, and AAV-mediated gene delivery strategy approaches to identify and functionally characterize early activated T cells responding to epithelial transformation (Aim 2); and employ uLIPSTIC-based proximity labelling, murine and human organoid–immune co-cultures to map direct interactions between epithelial cells and T cells in early CRC (Aim 3). By defining the earliest events that involve interactions between microbiota, epithelial cells and the immune system, this work will provide foundational insights into how mucosal homeostasis breaks down during cancer initiation, with broad implications for CRC prevention and epithelial immunoregulation, which are key priorities for the NIDDK.


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 = $916,243 )
2026	2026	ROCKEFELLER UNIVERSITY	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	10	9/11/2026	COMPETING CONTINUATION	$916,243
2026	2025	THE ROCKEFELLER UNIVERSITY	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	9	8/10/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $916,243

Issue Date FY: 2025 ( Subtotal = $522,060 )
2025	2025	ROCKEFELLER UNIVERSITY	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	9	5/2/2025	NON-COMPETING CONTINUATION	$522,060
														Subtotal = $522,060

Issue Date FY: 2024 ( Subtotal = $501,179 )
2024	2024	ROCKEFELLER UNIVERSITY	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	8	5/6/2024	NON-COMPETING CONTINUATION	$501,179
														Subtotal = $501,179

Issue Date FY: 2023 ( Subtotal = $522,060 )
2023	2023	ROCKEFELLER UNIVERSITY	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	7	4/5/2023	NON-COMPETING CONTINUATION	$522,060
														Subtotal = $522,060

Issue Date FY: 2022 ( Subtotal = $522,060 )
2022	2022	ROCKEFELLER UNIVERSITY, THE	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	6	4/8/2022	NON-COMPETING CONTINUATION	$522,060
2022	2021	ROCKEFELLER UNIVERSITY	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	5	11/12/2021	COMPETING CONTINUATION	$1,797
2022	2020	ROCKEFELLER UNIVERSITY	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	11/12/2021	NON-COMPETING CONTINUATION	-$1,797
														Subtotal = $522,060

Issue Date FY: 2021 ( Subtotal = $522,060 )
2021	2021	ROCKEFELLER UNIVERSITY, THE	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	5	6/7/2021	COMPETING CONTINUATION	$522,060
2021	2020	ROCKEFELLER UNIVERSITY, THE	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	5/28/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $522,060

Issue Date FY: 2020 ( Subtotal = $508,456 )
2020	2020	ROCKEFELLER UNIVERSITY, THE	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	4/3/2020	NON-COMPETING CONTINUATION	$508,456
														Subtotal = $508,456

Issue Date FY: 2019 ( Subtotal = $508,457 )
2019	2019	ROCKEFELLER UNIVERSITY, THE	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	4/16/2019	NON-COMPETING CONTINUATION	$508,457
														Subtotal = $508,457

Issue Date FY: 2018 ( Subtotal = $544,560 )
2018	2018	ROCKEFELLER UNIVERSITY, THE	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	4/23/2018	NON-COMPETING CONTINUATION	$477,810
2018	2018	ROCKEFELLER UNIVERSITY, THE	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	8/30/2018	SUPPLEMENT FOR EXPANSION	$66,750
														Subtotal = $544,560

Issue Date FY: 2017 ( Subtotal = $477,811 )
2017	2017	ROCKEFELLER UNIVERSITY, THE	1230 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	6/20/2017	NEW	$477,811
														Subtotal = $477,811

Grand Total All Awards = $5,544,946

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Defining mechanisms of epithelial surveillance by intestinal T cells

Award Number: R01DK113375

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: 07/01/2017

PERIOD OF PERFORMANCE END DATE: 06/30/2030

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer