Contents
Research
The Cardiac Mechanics Research Group uses experimental and computational models to investigate the relationships between the cellular and extracellular structure of cardiac muscle and the electrical and mechanical function of the heart during ventricular remodeling, repair and arrhythmia. The PIs are Drs. Andrew McCulloch, Jeff Omens, Roy Kerckhoffs and Anushka Michailova.
In vivo, genetically engineered mouse models are used for studies of the roles of cytoskeletal, sarcomeric, intercalated disk and membrane associated molecules in mechanotransduction and mechanoelectric feedback, ventricular hypertrophy and cardiomyopathy, post-myocardial infarction remodeling and regeneration, arrhythhmia mechanisms. These studies are conducted in collaboration with Cardiology faculty including Drs. Kirk Knowlton, Robert Ross, Ju Chen, and Kirk Peterson, and include the use of imaging modalities such as MRI and optical mapping.
In collaboration with Dr. Michael Berns, Robert Ross, we are investigating the single cell biophysics of ventricular myocytes in vitro subjected to localized loading using laser traps and FRET.
Tissue engineering of the cell microenvironment using microlithography and microfluidics are used to investigate the role of cell-cell and cell-matrix interactions in cardiac mechanical signaling, mechanoelectric feedback and the pathogenesis of heart failure. At present we are interested in methods to promote stem cell differentiation and integration for cardiac regenerative medicine. Collaborators in this research include Drs. Sylvia Evans, Karen Christman and Mark Mercola.
The systems biology of cardiac hypoxia responses are being studied in hypoxia, and the role of network structure in the development of combination drug therapies is also under investigation. Collaborators include Drs. Giovanni Paternostro and Jacob Feala.
Multi-scale computational modeling together with in-vitro experimental studies are used to investigate excitation-contraction coupling and contractile mechanisms and their regulation and the role of mechanoelectric feedback in action potential propagation. Collaborators include Drs. Michael Holst, J. Andrew McCammon, Mark Ellisman, Maryann Martone, Masa Hoshijima, Wolfgang Dillmann, Ju Chen and Philip Papadopoulous.
Experimental and computational studies of ventricular electromechanical interactions in the normal and failing heart are being used to investigate the relationships between alectrical activation sequence, regional structural and functional heterogeneities and regional 3D myocardial mechanics in vivo. These studies are being performed in collaboration with Professor James Covell and Dr. Larry Mulligan (Medtronic).
Patient-specific modeling based on non-invasive medical imaging and in-vivo clinical measurements is being used to explore atrial fibrillation and cardiac resynchronization therapy for heart failure, in collaboration with Dr. Sanjiv Narayan at the San Diego VA Medical Center. This work also relies on basic experimental studies in collaboration with Drs. James Covell and Larry Mulligan.
At present, the main research projects in the laboratory are:
Cardiac Biomechanics and Biophysics
- Ventricular remodeling and heart failure
- Ventricular electromechanics and pacing in heart failure
- Cardiac mechanoelectric feedback mechanisms
- Cardiac MRI
Cardiac Tissue Engineering and Regenerative Medicine
- Cardiac stem cells and regeneration
- Myocyte mechanotransduction and cardiomyopathy
Multi-Scale Modeling of the Heart
- Multi-scale computational modeling of cardiac excitation-contraction coupling
- Patient specific models for atrial fibrillation and heart failure
Cardiac Systems Biology
Genome-scale analysis of cardiac hypoxia in Drosophila
- Systems biology of combination drug therapies
Available Projects
We are currently accepting applications from undergraduate students, graduate students, and post-doctoral researchers interested in the following projects:
Modeling, in-vivo experiments and clinical studies of electrical pacing in congestive heart failure including patient-specific modeling of cardiac resynchronization therapy.
- Microscopic reconstruction, magnetic resonance imaging and multi-scale modeling of the mouse heart
- Multi-scale modeling of intracellular calcium transients in structurally detailed models of myocyte subcellular microanatomy
In-vitro studies of mechanoelectric feedback mechanisms using optical mapping in isolated hearts and myocytes.
In-vitro and in-vivo studies of mechanotransduction mechanisms in murine cardiac muscle.
Multi-scale modeling and in-vitro studies of signaling pathways regulating cardiac excitation-contraction coupling and myofilament interactions.
Systems biology of cardiac hypoxia in Drosophila and mice using microarrays, metabolomics and high-throughput phenotyping.
Studies of physical factors regulating cardiomyogenesis in stem-cell derived cardiac myocytes. Learn more...
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