Sunday, August 17, 2025 8/17/2025

Functional Contributions of the Noncoding Genome in Atherosclerosis Risk Factors

Award Number: K99HL175030
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 08/01/2025
PERIOD OF PERFORMANCE END DATE: 07/31/2027

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Functional Contributions of the Noncoding Genome in Atherosclerosis Risk Factors - PROJECT SUMMARY/ABSTRACT This application describes a five-year plan for my career development to define the contributions of mouse and human noncoding RNAs in cardiometabolic disorders. Sex differences are well-known in cardiometabolic diseases including atherosclerosis. There are significant numbers of long noncoding RNAs (lncRNAs) that have been implicated in executing functions in a highly context-specific manner, but their role in cardiovascular disease remains a work in progress. A major limitation to appreciating the significance of lncRNAs between sexes is the inability to test their function in vivo and having logical paradigms that prioritize lncRNA discovery. Thus, the overarching scientific goal of this application is to examine the contribution of long noncoding RNAs in hepatic lipid metabolism and their potential implications for cardiovascular and metabolic diseases. Leveraging an ambitious in vivo screen, I have prioritized and focused on one lncRNA, Xtendr, that shows lipid sensitive and highly sexually dimorphic effects. My preliminary data suggest that activating this lncRNA affects liver lipid content using the liver specific CRISPR modulation mice. Capitalizing on my preliminary data and the cutting- edge CRISPR activation and inhibition mouse models, I will test the influence and mechanism of Xtendr on hepatic lipid homeostasis and sex-specific hepatic traits (Aim 1). In Aim 2, I will capitalize on an advanced humanized liver mouse model that will be applied to interrogate the functional conservation of mouse lncRNAs with their syntenic human orthologs. Collectively, this project will reveal the importance of uncharacterized lncRNAs in sex dimorphic hepatic lipid metabolism within an in vivo system and uncover the challenging question about the complex relationships between sequence, synteny, and functional conservation.


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 = $129,137 )
2025	2025	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cardiovascular Diseases Research	000	1	7/23/2025	NEW	$129,137
														Subtotal = $129,137

Grand Total All Awards = $129,137

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Functional Contributions of the Noncoding Genome in Atherosclerosis Risk Factors

Award Number: K99HL175030

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 08/01/2025

PERIOD OF PERFORMANCE END DATE: 07/31/2027

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