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The role of apelin in the skeletal muscle during cancer cachexia development and recovery

Award Number: F30CA310112
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 05/18/2026
PERIOD OF PERFORMANCE END DATE: 05/17/2029

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The role of apelin in the skeletal muscle during cancer cachexia development and recovery - ABSTRACT The goal of this proposal is to elucidate the role of apelin in skeletal muscle during cancer cachexia (CC) development and recovery. CC affects multiple organs and failure to recover from the condition ultimately leads to death. CC results in decreased physical ability, reduced therapy efficacy, and increased mortality and morbidity. CC is estimated to affect as many as 80% of patients with cancer and accounts for up to 20% of cancer deaths. The Janowitz lab and others have identified interleukin (IL)-6, as well as other circulating factors and hormones, as drivers of CC development. However, targetable mechanisms underlying CC remain to be discovered, and there are no effective treatments for patients with CC. Studying CC from a recovery perspective may lead to identification of treatments that could improve patient health and enhance cancer therapy responses. I have developed a CC mouse model in which both CC development and recovery can be studied in the same animal. Using this model, I observed decreased muscle mass during CC development and increased muscle mass during CC recovery. By analyzing quadriceps RNA sequencing data from cachectic and recovering mouse, I identified increased denervation during CC development and increased reinnervation during CC recovery. This suggests that neuromuscular junctions (NMJ) may play a role in muscle atrophy and regeneration in CC. By focusing my analyses on circulating hormones, I identified apelin as the most upregulated hormone in the skeletal muscle during CC recovery. Apelin is anti-inflammatory and is involved in metabolism and muscle regeneration. My hypothesis is that apelin contributes to muscle atrophy and regain in CC development and recovery through NMJ disassembly and reassembly. In Aim 1, I will use scRNA-seq to identify the cells expressing apelin and the apelin receptor during CC development and recovery. I will modulate apelin levels, both locally and systemically, to determine the importance of apelin signaling in muscle during CC development and recovery. In Aim 2, I will investigate the causes of NMJ disassembly and reassembly in CC. I will perform casual-inference analysis to confirm the role of apelin in driving muscle recovery and identify additional targets contributing to CC recovery. I will interrogate the cascade connecting apelin and NMJ by altering apelin downstream neurotrophic factor brain- derived neurotrophic factor. I will analyze the results of both Aims using survival and recovery data, weight and muscle mass measurements, and NMJ gene expression changes. Finally, I will utilize co-detection by indexing (CODEX) and whole-tissue imaging to quantify denervation and reinnervation with or without genetics modulations. Through this project, I will uncover the role of apelin in skeletal muscle during CC development and recovery and identify possible treatment targets that could prevent CC or facilitate CC recovery.


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 = $42,647 )
2026	2026	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Research Manpower	000	1	4/29/2026	NEW	$42,647
2026	2026	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	W5510 FRANKS MELVILLE MEMORIAL LIBRARY	STONY BROOK	NY	11794	SUFFOLK	USA	Cancer Research Manpower	001	1	4/29/2026	NEW	$0
														Subtotal = $42,647

Grand Total All Awards = $42,647

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The role of apelin in the skeletal muscle during cancer cachexia development and recovery

Award Number: F30CA310112

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 05/18/2026

PERIOD OF PERFORMANCE END DATE: 05/17/2029

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