Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Mechanistic Understanding of Hypoxia-Induced Peroxisome loss: Implications for Heart Failure

Award Number: K99HL163396
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 06/01/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2023

Group Awards By:

View Award Description

Mechanistic Understanding of Hypoxia-Induced Peroxisome loss: Implications for Heart Failure - Project Summary/Abstract Heart failure is characterized by decreased fatty acid oxidation (FAO) and increased glycolysis. Increasing FAO is beneficial in animal models of heart failure however why it is beneficial is unclear. FAO inhibition during heart failure occurs in part due to increased hypoxia during ischemia and ischemic cardiomyopathy now accounts for nearly 70% of heart failure cases. The mechanisms by which hypoxia inhibits FAO remain poorly understood. FAO is compartmentalized into mitochondria and peroxisomes. I have discovered that HIFa, the master regulator in the response to hypoxia, depletes peroxisomes. Mechanistically. I have identified HIFa activates DEPP1, a protein of unknown function that is necessary and sufficient for hypoxia- induced peroxisome loss. In Aim 1, I propose complementary biochemical and genetic experiments to identify the mechanism of DEPP1-mediated peroxisome loss. In Aim 2, I will determine how DEPP1 loss reduces cardiomyocyte death during chronic HIFa activation. In Aim 3, I propose to test the role of DEPP1 in ischemic cardiomyopathy animal models. These studies will contribute to the understanding of how heart failure inhibits FAO and identify a novel mechanism in heart failure. I am a biologist with a background in metabolism and nutrient sensing, applying for a K99 award with the long-term goal of becoming a tenure-track, independent laboratory investigator. I envision developing a research program focused on how the common pathophysiology of limited oxygen availability regulates metabolism at the cellular, tissue, and organismal level to ultimately harness that knowledge to develop new therapies for ischemic diseases, such as heart failure and stroke. During my proposed K99 research training, I will perform mentored research in the lab of Dr. William Kaelin at the Dana-Farber Cancer Institute (DFCI), a world’s expert in oxygen sensing. In the K99 phase of this award, I will focus on identifying the mechanism by which DEPP1 mediates hypoxia-induced peroxisome loss. As I transition into the R00 phase of this award, I will determine how maintaining peroxisome function reduces cardiac death during ischemia and test the role of DEPP1 in animal models of ischemic cardiomyopathy. I have assembled an expert scientific advisory committee to help guide my development including: Dr. Bruce Spiegelman (DFCI/HMS), Dr. Jean Schaffer (Joslin/HMS), Dr. Christine Seidman (HMS), and Dr. John Asara (BIDMC/DFCI). I believe that training at DFCI, a world-class clinical and research environment, along with additional coursework and conferences will help me achieve my long-term career goals.


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: 2024 ( Subtotal = -$76 )
2024	2022	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cardiovascular Diseases Research	000	1	1/22/2024	NEW	-$76
														Subtotal = -$76

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cardiovascular Diseases Research	000	1	6/16/2023	NEW	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $149,850 )
2022	2022	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02115	SUFFOLK	USA	Cardiovascular Diseases Research	000	1	5/26/2022	NEW	$149,850
														Subtotal = $149,850

Grand Total All Awards = $149,774

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Mechanistic Understanding of Hypoxia-Induced Peroxisome loss: Implications for Heart Failure

Award Number: K99HL163396

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 06/01/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2023

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer