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Tuft cell heterogeneity in function, lineage, and structure in ileal inflammatory disease

Award Number: R01DK103831
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY/ABSTRACT Inflammatory Bowel Disease (IBD) and its subtype Crohn’s disease (CD) arise due to a loss of tolerance to environmental antigens in genetically susceptible individuals. Longitudinal analysis has identified an inverse correlation between rates of communicable parasitic diseases and IBD, a phenomenon termed the “hygiene hypothesis.” Tuft cells have recently been identified as a critical component for sensing and responding to parasitic infections. Our lab has recently identified that tuft cells may be heterogeneous in their lineage and function in microbiome response, and specific populations may be critical for mitigating inflammation in ileal inflammatory disease. Here, we propose innovative experimental and computational approaches to dissect the heterogeneity of tuft cell lineage, structure, and function as they relate to regulating immune responses in in vivo models of CD. In aim 1, we will conduct single-cell sequencing, high resolution microscopy, and functional secretory assays to understand lineage-structure-function relationships in different tuft cell populations in mouse and enteroid models. In aim 2, we utilize multiplex imaging, Cytometry Time-of-Flight (CyTOF), and cytokine profiling to probe the downstream tuft-type 2 response network by utilizing several chemical and genetic models of pathway ablation. Through our findings, we aim to make significant contributions to the current understanding of tuft cell biology and epithelial-microbiome crosstalk in the intestine. Ultimately, this research will allow us to diagnose, stratify, and, ultimately, treat patients with IBD and expand the pool of targets in this complex, multifactorial 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: 2024 ( Subtotal = $525,097 )
2024	2024	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	9	2/5/2024	NON-COMPETING CONTINUATION	$525,097
														Subtotal = $525,097

Issue Date FY: 2023 ( Subtotal = $583,441 )
2023	2023	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	8	2/17/2023	NON-COMPETING CONTINUATION	$583,441
														Subtotal = $583,441

Issue Date FY: 2022 ( Subtotal = $617,739 )
2022	2022	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	005	7	4/6/2022	NON-COMPETING CONTINUATION	$58,345
2022	2022	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	004	7	3/30/2022	NON-COMPETING CONTINUATION	$0
2022	2022	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	7	3/14/2022	SUPPLEMENT FOR EXPANSION	$34,298
2022	2022	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	7	3/10/2022	NON-COMPETING CONTINUATION	$525,096
2022	2021	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	6	3/24/2022	COMPETING CONTINUATION	$733
2022	2020	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	5	3/24/2022	NON-COMPETING CONTINUATION	-$733
														Subtotal = $617,739

Issue Date FY: 2021 ( Subtotal = $644,558 )
2021	2021	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	6	7/31/2021	COMPETING CONTINUATION	$12,645
2021	2021	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	6	8/6/2021	SUPPLEMENT FOR EXPANSION	$47,193
2021	2021	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	004	6	9/20/2021	SUPPLEMENT FOR EXPANSION	$0
2021	2021	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	6	2/2/2021	COMPETING CONTINUATION	$597,365
2021	2020	VANDERBILT UNIVERSITY, THE	2301 VANDERBILT PL	NASHVILLE	TN	37235	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	5	7/31/2021	NON-COMPETING CONTINUATION	-$12,645
														Subtotal = $644,558

Issue Date FY: 2020 ( Subtotal = $353,250 )
2020	2020	VANDERBILT UNIVERSITY, THE	2301 VANDERBILT PL	NASHVILLE	TN	37235	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	5	2/11/2020	NON-COMPETING CONTINUATION	$35,325
2020	2020	VANDERBILT UNIVERSITY, THE	2301 VANDERBILT PL	NASHVILLE	TN	37235	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	1/28/2020	NON-COMPETING CONTINUATION	$317,925
														Subtotal = $353,250

Issue Date FY: 2019 ( Subtotal = $376,005 )
2019	2019	VANDERBILT UNIVERSITY, THE	2301 VANDERBILT PL	NASHVILLE	TN	37235	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	2/1/2019	NON-COMPETING CONTINUATION	$376,005
														Subtotal = $376,005

Issue Date FY: 2018 ( Subtotal = $412,791 )
2018	2018	VANDERBILT UNIVERSITY, THE	2301 VANDERBILT PL	NASHVILLE	TN	37235	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	5/1/2018	NON-COMPETING CONTINUATION	$41,279
2018	2018	VANDERBILT UNIVERSITY, THE	211 KIRKLAND HALL	NASHVILLE	TN	37240	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	12/14/2017	NON-COMPETING CONTINUATION	$371,512
														Subtotal = $412,791

Issue Date FY: 2017 ( Subtotal = $422,178 )
2017	2017	VANDERBILT UNIVERSITY, THE	211 KIRKLAND HALL	NASHVILLE	TN	37240	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	2	6/22/2017	NON-COMPETING CONTINUATION	$138,102
2017	2017	VANDERBILT UNIVERSITY, THE	211 KIRKLAND HALL	NASHVILLE	TN	37240	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	1/4/2017	NON-COMPETING CONTINUATION	$356,313
2017	2017	VANDERBILT UNIVERSITY, THE	211 KIRKLAND HALL	NASHVILLE	TN	37240	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	2	9/12/2017	SUPPLEMENT FOR EXPANSION	$26,274
2017	2017	VANDERBILT UNIVERSITY, THE	211 KIRKLAND HALL	NASHVILLE	TN	37240	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	6/21/2017	NON-COMPETING CONTINUATION	-$98,511
														Subtotal = $422,178

Issue Date FY: 2016 ( Subtotal = $408,183 )
2016	2016	VANDERBILT UNIVERSITY HOSPITAL, CHILDREN'S REHAB UNIT	1161 21ST AVENUE SOUTH	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	2/3/2016	NEW	$408,183
														Subtotal = $408,183

Grand Total All Awards = $4,343,242

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Tuft cell heterogeneity in function, lineage, and structure in ileal inflammatory disease

Award Number: R01DK103831

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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