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Efferent vagal modulation of neuropod cells in the small intestine

Award Number: K01DK131403
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 03/20/2025
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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Efferent vagal modulation of neuropod cells in the small intestine - ABSTRACT Functional gastrointestinal (GI) diseases are the most common diagnoses in gastroenterology. Such disorders, like irritable bowel syndrome or functional dyspepsia, are recognized by altered GI sensitivity and motility. Though the pathophysiology is complex, a conserved feature is the bidirectional alteration in brain- gut signaling. Thus, these are classified as disorders of brain-gut interaction. While the vagus nerve is the main brain-gut link, how the brain relays neural signals that modulate GI epithelial sensory function is unknown. My long-term career goal is to document how neural circuits originating from the brain alter the gut’s ability to sense nutrients. With the support of the NIH Mentored Research Scientist Development Award — K01, the objective of this proposal is to delineate a brain-to-gut neural circuit that could be used to alter sensory transduction at the gut epithelium. This will be accomplished in three aims: Aim 1. Determine the neurotransmitters and hormones released by intestinal sensory cells in response to excitatory neurotransmitter stimulation. An in vitro organoid and sorted single cell assay will be used to measure release in culture. This aim will demonstrate that an excitatory neurotransmitter can stimulate vesicular release in enteroendocrine cells. Aim 2. Pair vagal stimulation with sensory epithelial cell calcium imaging and electrophysiology to evaluate the functional connectivity of vagal neurons synapsing onto intestinal sensory cells. This aim will demonstrate a functional connection where neurons increase the excitability of sensory cells in the proximal small intestine. Aim 3. Utilize both retrograde (post- to pre-synapse) rabies virus and anterograde (pre- to post- synapse) herpes simplex virus to trace a mono-synaptic connection between the brainstem and intestinal sensory epithelial cells. This aim will establish an anatomical map for how the brainstem is connected to neuropod cells. Identifying functional neural circuits connecting the brain and the gut will enable the understanding of the mechanisms behind visceral hypersensitivity. Together with my mentoring team, we have designed this project to provide me with the necessary research and professional training for me to excel as an independent investigator in the field of sensory neurogastroenterology.


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 = $155,304 )
2026	2026	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	6/1/2026	NON-COMPETING CONTINUATION	$155,304
														Subtotal = $155,304

Issue Date FY: 2025 ( Subtotal = $155,304 )
2025	2025	UNIVERSITY OF ARIZONA	845 N PARK AVE RM 538	TUCSON	AZ	85721	PIMA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	4	8/20/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$155,304
2025	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	3	8/26/2025	NON-COMPETING CONTINUATION	$0
2025	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	8/19/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $155,304

Issue Date FY: 2024 ( Subtotal = $118,770 )
2024	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	5/20/2024	NON-COMPETING CONTINUATION	$118,770
														Subtotal = $118,770

Issue Date FY: 2023 ( Subtotal = $118,770 )
2023	2023	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	6/2/2023	NON-COMPETING CONTINUATION	$118,770
														Subtotal = $118,770

Issue Date FY: 2022 ( Subtotal = $120,270 )
2022	2022	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	8/12/2022	NEW	$120,270
														Subtotal = $120,270

Grand Total All Awards = $668,418

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Efferent vagal modulation of neuropod cells in the small intestine

Award Number: K01DK131403

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 03/20/2025

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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