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Understanding the development and function of a newly discovered intestinal cell type

Award Number: R00HD115786
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2026
PERIOD OF PERFORMANCE END DATE: 04/30/2029

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Understanding the development and function of a newly discovered intestinal cell type - PROJECT SUMMARY (See instructions): The long-term goal of this project is to characterize the transcriptional regulation underlying development and understand function of a newly discovered intestinal cell type called best4+ cells, that is depleted in inflammatory bowel disease patients, It is however unresolved whether best4+ cell loss causes disease or whether disease kills best4+ cells, Improper differentiation of intestinal cells often leads to loss of specialized functions that manifest in disease, Since it is not well understood how best4+ cells contribute to intestinal homeostasis and how their dysfunction leads to disease, this proposal also focuses on understanding the function of best4+ cells, The function of best4+ cells remain largely unknown in any organism; however, previous single-cell profiling predicted some physiological roles such as pH sensing, electrolyte homeostasis, and regulation of satiety, Since best4+ cells are absent from mouse models, experiments will ablate best4+ cells in the zebrafish intestine and study the response of other intestinal cell types using single-cell RNA sequencing as well as measure disease hallmarks in the intestine (pH changes, epithelial barrier loss, inflammation etc,), Furthermore, factors predicted from single-cell RNAseq studies will be perturbed to understand the roles of each of these genes in regulating overall best4+ cell function, To test the alternate hypothesis whether best4+ cell loss is a symptom of disease rather than cause, this proposal will also induce inflammation in the zebrafish intestine in the presence and absence of best4+ cells to characterize how various intestinal cells including best4+ cells respond to changes in the intestinal environment and what aspects of the overall intestinal response to disease is regulated by best4+ cells.


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 = $249,000 )
2026	2026	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Child Health and Human Development Extramural Research	000	2	5/7/2026	EXTENSION WITH OR WITHOUT FUNDS	$249,000
														Subtotal = $249,000

Grand Total All Awards = $249,000

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Understanding the development and function of a newly discovered intestinal cell type

Award Number: R00HD115786

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2026

PERIOD OF PERFORMANCE END DATE: 04/30/2029

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