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The Role of SCN-expressed Ghrelin Receptors (GHSRs) in Time-of-Day Aligned Feeding

Award Number: F30DK145145
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 07/01/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2030

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The Role of SCN-expressed Ghrelin Receptors (GHSRs) in Time-of-Day Aligned Feeding - PROJECT SUMMARY/ABSTRACT Circadian rhythms are vital to overall health. These ~24-hour cycles regulate behavior, physiology, and molecular functions, enabling organisms to anticipate daily environmental changes. However, modern 24/7 lifestyles increasingly lead to circadian misalignment – a mismatch between internal biological clocks and the external environment. This misalignment can result in abnormal behaviors, such as nighttime eating or difficulty staying awake in the daytime. Both human and animal studies link circadian disruption to poor metabolic outcomes. This is especially relevant today, as over 43% of U.S. adults are overweight and more than 16% live with obesity. While the association between circadian misalignment and metabolic health is well-documented, the biological mechanisms behind this link remain unclear. Understanding these mechanisms would directly support the NIDDK’s mission to advance knowledge of metabolic disease and improve human health. A promising candidate linking circadian biology and metabolism is the hormone ghrelin. Ghrelin is secreted by gastric mucosal cells in response to fasting or in anticipation of food and powerfully stimulates hunger while decreasing energy expenditure. Ghrelin acts on the brain via its receptor, GHSR, which is expressed in multiple regions. One region with high GHSR expression is the primary circadian clock – the suprachiasmatic nucleus (SCN) of the hypothalamus. However, the role of GHSRs in the SCN is not known. This proposal tests the hypothesis that GHSRs in the SCN help regulate feeding behavior and circadian alignment of food intake. Aim 1 will determine whether GHSR expression in the SCN is necessary and sufficient for proper circadian feeding patterns. This will be done by selectively deleting or re-expressing GHSR in SCN neurons, then measuring food intake rhythms and responses to peripheral ghrelin. Aim 2 will explore whether SCN GHSRs contribute to night eating syndrome (NES), a disorder characterized by delayed and dysregulated feeding. It is predicted that disrupting GHSR expression in the SCN will lead to abnormal feeding rhythms and that restoring GHSR to the SCN may may be sufficient to recover circadian alignment of feeding. In addition, SCN GHSRs may contribute to the development and symptoms of NES. This research will be conducted under the co- mentorship of Dr. Jeffrey Zigman and Dr. Joseph Takahashi at UT Southwestern Medical Center. Dr. Zigman is a leader in ghrelin biology, and Dr. Takahashi is a pioneer in circadian research. Their combined expertise offers an ideal environment for mentorship and collaboration. In addition to advancing scientific understanding, this project will provide the applicant with hands-on training in genetic mouse model development, circadian data analysis, and neural control of metabolism. These skills will serve as a foundation for a future career as a physician-scientist. Through this fellowship, the applicant will also develop critical professional competencies, including scientific writing, leadership, and networking – key elements for long-term success in translational biomedical research.


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 = $41,448 )
2026	2026	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	6/16/2026	NEW	$41,448
2026	2026	THE UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	6/16/2026	NEW	$0
														Subtotal = $41,448

Grand Total All Awards = $41,448

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The Role of SCN-expressed Ghrelin Receptors (GHSRs) in Time-of-Day Aligned Feeding

Award Number: F30DK145145

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 07/01/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2030

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