Ongoing Projects

1. Structural and functional basis of myocardial dysregulation in genetic cardiomyopathy

R01HL172492    06/2024 – 06/2028

NHLBI                               

Major Goals: The proposed activities aim to investigate the structural basis of cardiomyopathies resulting from sarcomere protein variants, revealing the translational mechanistic understanding necessary to treat these diseases.

2. Thick filament regulation mechanisms in healthy and diseased myocardium

R01HL171657        12/2023 – 11/2028

NHLBI                            

Major Goals: This project aims to understand the thick filament-based regulation in large mammalian hearts.

3. The Biophysics Collaborative Access Team

P30GM138395  01/2021 – 12/2025

NIGMS                           

Major Goals: To operate BioCAT facilities for X-ray diffraction and scattering from non-crystalline biological as a mature synchrotron facility for a national and international community of collaborators and service users.

4. Analysis tools for fiber diffraction of muscle

5R01GM144555    06/2022 – 05/2026

NIGMS                               

Major Goals: This project aims to develop a comprehensive software suite for analyzing and interpreting data from synchrotron small-angle X-ray diffraction studies of muscle.

Collaborative projects

MuscleX lab collaborates with more than 15 groups from all over the world, with a turnover rate of 2-3 groups per year. Being scientifically involved with multiple interdisciplinary projects gives lab members tremendous opportunities to broaden their knowledge and make invaluable collaborative relationships.

Selected current collaborative projects:

*In collaboration with Mike Regnier (5R01HL128368) from the University of Washington, we want to understand why deoxy-ATP can improve cardiac muscle performance.

*In collaboration with Henk Granzier (R01AR053897) from the University of Arizona, we want to study the novel nebulin/Lmod2 dual regulation system of thin filament length and include a focus on whether upregulating Lmod2 in NEM2 can ameliorate muscle weakness

*In collaboration with Henk Granzier (R01AR083233) from the University of Arizona, we want to understand how mutations in titin alter thick filament-based regulation of skeletal muscle

*In collaboration with Coen Ottenheijm (R01HL121500) from the University of Arizona, we want to understand why the diaphragm is so extremely sensitive to inactivity during mechanical ventilation, and we will test the novel concept that the giant elastic muscle protein titin plays a central role

* In collaboration with David Kass and Steven Hsu (R01HL172830) from Johns Hopkins University, we want to investigate thick filament dysregulation in human heart failure and how novel small-molecule myotropes might ameliorate the disease pathology.