Thursday, September 18, 2025 9/18/2025

Molecular Drivers of FABP-mediated Endocannabinoid Signaling for Appetite Regulation

Award Number: R16GM145403
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2022
PERIOD OF PERFORMANCE END DATE: 07/31/2026

Group Awards By:

View Award Description

Molecular Drivers of FABP-mediated Endocannabinoid Signaling for Appetite Regulation - Stark, Ruth E. Molecular Drivers of FABP-mediated Endocannabinoid Signaling for Appetite Regulation Metabolic signaling by endogenous cannabinoids (ECs) is essential to the regulation of human appetite, pain, and neuroprotection. Fatty acid-binding proteins (FABPs) can either sequester the hydrophobic ECs or transport them to hydrolytic enzymes; ECs routed to the nucleus also activate the peroxisome proliferator-activated receptors (PPARs). EC levels have been correlated with obesity in knockout mice for liver (L) FABP that is co-expressed with intestinal (I) FABP in enterocytes and also for PPARa knockouts, underscoring the regulatory roles of these proteins. We will probe poorly understood EC-FABP, EC-PPAR, and FABP-EC-PPAR complexes in vitro at near-physiological concentrations, determining affinities, metabolic fates, molecular binding interfaces, and conformational changes to test mechanistic hypotheses regarding EC signaling. Trainees at multiple career stages, including those recruited from underrepresented groups in STEM, will be integrally involved in this research program. Specific questions to be addressed are as follows: (1) How do ECs choose between FABP chaperones to produce obese or lean outcomes? The possibility that ECs are delivered by LFABP to hydrolytic enzymes for metabolic breakdown rather than sequestered by IFABP in the enterocyte will be tested enzymatically, whereas the rationale for LFABP’s diminished affinity will be explored using high- pressure solution-state NMR to identify energetically favored candidate sites for binding. (2) Could transcriptional activity be driven by EC binding preferences for LFABP vs. PPARa? The PPARa ligand-binding domain (PPARa_LBD) will be purified, rigorously delipidated, and tested in vitro for EC- modulated transcriptional activity. EC binding affinities will be compared for PPARa_LBD and FABPs. (3) Could transcriptional activity be driven by EC-modulated FABP-PPAR collisions that cause conformational changes? To determine the interactions involved in the proposed FABP-mediated EC activation of PPARa transcriptional function, we will first use surface plasmon resonance to measure the binding affinity of LFABP-PPARa_LBD protein complexes, on their own and in the presence of ligands with a range of known activation efficacies. The site-specific collision-associated impact on the LFABP partner will be probed by solution-state NMR spectroscopy of the [U-15N]-enriched protein, using chemical shift perturbations of each backbone NH resonance to define the binding interface with PPARa_LBD, any allosteric structural changes that occur upon complex formation, and their modulation by EC ligands. Taken together, these experiments will advance our understanding of (macro)molecular networks that function to achieve metabolic signaling by ECs involved in appetite and pain regulation, thereby advancing our understanding of health risks related to obesity and inflammation. This understanding can guide the design of drugs that modulate these biomedically important ligand-protein and protein-protein interactions. NIH SuRE Grant Proposal


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: 2025 ( Subtotal = $234,402 )
2025	2025	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Biomedical Research and Research Training	000	4	8/6/2025	NON-COMPETING CONTINUATION	$157,000
2025	2025	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Biomedical Research and Research Training	001	4	8/7/2025	SUPPLEMENT FOR EXPANSION	$77,402
														Subtotal = $234,402

Issue Date FY: 2024 ( Subtotal = $393,042 )
2024	2024	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Biomedical Research and Research Training	001	3	7/23/2024	NON-COMPETING CONTINUATION	$157,000
2024	2024	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Biomedical Research and Research Training	000	2	6/18/2024	SUPPLEMENT FOR EXPANSION	$15,480
2024	2024	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Biomedical Research and Research Training	005	3	8/29/2024	SUPPLEMENT FOR EXPANSION	$25,374
2024	2024	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Biomedical Research and Research Training	002	2	7/31/2024	SUPPLEMENT FOR EXPANSION	$2,308
2024	2024	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Biomedical Research and Research Training	004	3	8/28/2024	SUPPLEMENT FOR EXPANSION	$99,999
2024	2024	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Biomedical Research and Research Training	003	3	8/1/2024	SUPPLEMENT FOR EXPANSION	$92,881
														Subtotal = $393,042

Issue Date FY: 2023 ( Subtotal = $255,799 )
2023	2023	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Biomedical Research and Research Training	001	2	9/5/2023	SUPPLEMENT FOR EXPANSION	$98,799
2023	2023	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Biomedical Research and Research Training	000	2	7/17/2023	NON-COMPETING CONTINUATION	$157,000
														Subtotal = $255,799

Issue Date FY: 2022 ( Subtotal = $154,150 )
2022	2022	RESEARCH FOUNDATION OF THE CITY UNIVERSITY OF NEW YORK	160 CONVENT AVE	NEW YORK	NY	10031	NEW YORK	USA	Biomedical Research and Research Training	000	1	8/12/2022	NEW	$154,150
														Subtotal = $154,150

Grand Total All Awards = $1,037,393

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Molecular Drivers of FABP-mediated Endocannabinoid Signaling for Appetite Regulation

Award Number: R16GM145403

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/15/2022

PERIOD OF PERFORMANCE END DATE: 07/31/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer