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

Mechanisms of Sarcomere Functional Remodeling in the Postprandial Python Heart

Award Number: F31HL184667
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 06/01/2026
PERIOD OF PERFORMANCE END DATE: 05/31/2028

Group Awards By:

View Award Description

Mechanisms of Sarcomere Functional Remodeling in the Postprandial Python Heart - PROJECT SUMMARY/ABSTRACT Common pathological signatures of heart failure include decreased contractility and increased stiffness, leading to decreased cardiac output. Identifying the underlying molecular mechanisms behind these phenotypes is critical for targeted therapeutic development to address heart disease. Pythons represent a unique model organism to study cardiac hypertrophy and altered cardiac function. After feeding, pythons undergo rapid physiological cardiac hypertrophy within 72 hours, followed by subsequent regression. Recent work from our lab also showed that pythons rapidly increase cardiac myofibril active tension and decrease myofibril passive tension after feeding. Identifying the regulatory mechanisms that promote rapid tension changes in the post-fed python heart may allow for the discovery of novel, conserved mechanistic targets for modifying cardiac function in humans. We conducted a preliminary global phospho-proteomics study with samples from fasted and fed ball python ventricles. I identified 19 differentially phosphorylated resides on cardiac myosin heavy chain (a key determinant of active tension/force) and 133 differentially phosphorylated sites on titin (a key determinant of passive tension). The majority of these sites are conserved in humans and reside within known myosin and titin functional domains. We have also generated biochemical data suggesting that ATP turnover of myosin is altered after feeding. The goals of this work are to further our mechanistic understanding of how phosphorylation of specific residues regulates titin stiffness and be the first study to assess how phosphorylation in the motor domain and proximal rod region affects myosin heavy chain function. Specifically, I will conduct single molecule atomic force microscopy (with the Perkins Lab at CU Boulder) and thermodynamic stability assays to determine how phospho-mimetic mutations affect the elastic and thermodynamic properties of titin. I will also use phospho-null/mimetic mutations within the motor and proximal rod regions of cardiac myosin heavy chain to mimic changes that occur after feeding and characterize the impact on myosin function and structural states with biochemical and electron microscopy assays. My long- term goals are to identify how pythons rapidly tune cardiac function and undergo hypertrophy in a physiological fashion (specifically through alternative splicing and post-translational modifications), and how this compares with mammalian models of physiological and pathological remodeling. This fellowship will allow me to learn single molecule force microscopy techniques from world-leading experts, gain expertise with myosin functional assays that our lab has significant experience in, and improve my background in muscle biophysics. These skills will help prepare me for a future career as an independent investigator in the field of cardiac remodeling.


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 = $43,527 )
2026	2026	THE REGENTS OF THE UNIVERSITY OF COLORADO	3100 MARINE ST	BOULDER	CO	80309	BOULDER	USA	Cardiovascular Diseases Research	001	1	5/7/2026	NEW	$0
2026	2026	THE REGENTS OF THE UNIVERSITY OF COLORADO	3100 MARINE ST	BOULDER	CO	80309	BOULDER	USA	Cardiovascular Diseases Research	000	1	5/7/2026	NEW	$43,527
														Subtotal = $43,527

Grand Total All Awards = $43,527

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Mechanisms of Sarcomere Functional Remodeling in the Postprandial Python Heart

Award Number: F31HL184667

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 06/01/2026

PERIOD OF PERFORMANCE END DATE: 05/31/2028

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer