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Enteric neurochemical plasticity and its modulation for future personalized treatment for enteric neuropathies

Award Number: R21HD118634
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: 06/01/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2028

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Enteric neurochemical plasticity and its modulation for future personalized treatment for enteric neuropathies - PROJECT SUMMARY Enteric neuropathies are serious conditions caused by abnormalities in the enteric nervous system (ENS), an extensive neural network that spans the entire gastrointestinal tract and controls gut functions. Reduction in number of neuronal nitric oxide synthesis (nNOS) expressing enteric neurons is a hallmark of many human gastrointestinal diseases, including esophageal achalasia, gastroparesis, and Chagas disease. Despite the prevalence of these conditions and the morbidity they cause, current treatment options are significantly limited and do not directly address the underlying pathophysiology. Cell therapy represents a novel, curative approach to alleviating enteric neuropathies by replacing the absent or injured neurons. Although we have achieved significant successes in our preclinical cell therapy studies using animal models of enteric neuropathy, an enteric neural cell therapy approach specifically tailored for nNOS-deficient diseases would be a significant advance. Recent studies, and our own preliminary experiments, have demonstrated that enteric neural stem cells (ENSCs) generate two neuronal classes that subsequently differentiate into specific phenotypes and that this process includes phenotype switching. This led us to hypothesize that manipulation of this enteric neurochemical plasticity (ENCP) would allow us to optimize ENSC therapy by generating therapeutically relevant, disease- specific neuron subtypes. By utilizing optimized ENSC culture conditions, cell transplantation techniques, transcriptomic analysis, and genetic manipulation, we propose to test our hypothesis that enteric neuronal subtype plasticity occurs postnatally and can be leveraged for cell therapy application. We will also elucidate the role of the transcription factors, Pbx3 and Tbx3 in postnatal ENCP. The proposed studies will advance our understanding of the mechanisms underlying cell commitment in the ENS and how this knowledge could be leveraged to optimize the therapeutic efficacy of cell therapy applications in the future.


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 = $397,173 )
2026	2026	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Child Health and Human Development Extramural Research	001	1	6/25/2026	NEW	$0
2026	2026	THE GENERAL HOSPITAL CORPORATION	55 FRUIT ST	BOSTON	MA	02114	SUFFOLK	USA	Child Health and Human Development Extramural Research	000	1	5/27/2026	NEW	$397,173
														Subtotal = $397,173

Grand Total All Awards = $397,173

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Enteric neurochemical plasticity and its modulation for future personalized treatment for enteric neuropathies

Award Number: R21HD118634

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: 06/01/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2028

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