CT Surgery Research Lab
Research Director: J. Yasha Kresh, Ph.D.
Learning and scholarly interaction are fostered in an atmosphere of discovery within the Cardiothoracic Research and Cardiovascular Biophysics Laboratory, which is an interdisciplinary core facility bridging the Department of Cardiothoracic Surgery and the Division of Cardiovascular Diseases. The research projects draw on a large multidisciplinary knowledge base, applying the principles, phenomena, techniques, and technology of cardiovascular engineering, cellular and tissue engineering, biophysics, mathematical/computational biology and systems theory to the solution of basic and clinical cardiovascular problems.
The broad range of research projects that been pursued reflects this unique interdisciplinary approach. Importantly, this facility also serves as an educational cardiac research center to direct the scientific projects of medical and surgical residents, as well as graduate and medical students.
In addition, the collaborative efforts include projects with the Tissue Engineering, Cellular Mechanics and BIOMEMS groups at Drexel University and University of Pennsylvania.
Our research effort consists of:
1. Projects focused on the mechanobiology and surgical engineering of end-stage heart-failure
This overarching effort includes investigation of:
- Cardiac mechanotransduction in heart failure and recovery
- Topobiology of cellular cardiomyoplasty (milieu-dependent cardiomyocyte differentiation and adaptation)
- Imaging and assessment of remodeled human hearts (structure and biomechanics)
- Effects of cardiac-assist devices on cellular structure, function and reverse-remodeling
- Surgical cardioplasty (design of ventricular reshaping and constrainment devices)
2. Efforts to improve the capabilities of robot-assisted cardiac surgery, through the incorporation of smart sensors and manipulators with haptic (tactile) feedback
- Computer-assisted surgical planning, endoscopic manipulators
Cardiac Mechanotransduction in Failure and Recovery
In this study we are testing the hypothesis that cardomyocytes sense and respond to alterations in their mechanical microenvironment via different mechanisms depending on the timing of mechanical load within the cardiac cycle. Based on this concept, we believe that myocyte mechanical loading can be manipulated to promote reverse remodeling in heart failure. This multidisciplinary research project will address the role that mechanical load-dependent events play in establishing the fine balance between myocyte remodeling and recovery (‘reverse remodeling’), as well as advance our understanding of interaction between myocyte contractile function (calcium cycling) and mechanosensing. The mechanistic insight into load-induced cardiac remodeling will help identify biologically rationalized surgical and medical therapies to maximize cardiac function recovery. We may discover new myocyte cytoskeletal targets for pharmacological therapies that mimic the beneficial effects of mechanical reprogramming (mechanical unloading, surgical reshaping/remodeling). The transplational offshoot is the engineering of novel surgical reconstructive and tissue repair strategies (e.g. injectable matrix scaffolds).
Cellular Repair and Regeneration: Topobiology of Stem Cells
Our work is focused on cell based therapy for heart failure. The goal is to utilize autologous human stem (adult stromal bone marrow, i.e., mesenchymal) cells (hMSC) for the repair and /or regeneration of the damaged cardiac tissue.
In particular, understanding the microenvironment-dependent (target niche) signals (e.g. growth factors, cytokines) that can induce transdifferentiation of hMSC to cardiac phenotype is of paramount importance. The Microarray-based gene expression profiling technology will enable us to identify the key network of genes that are activated by the various ex-vivo imposed culture conditions (e.g. growth factors, ECM, mechanical/electrical "preconditioning"). Understanding the conditions and cues involved in controlling the plasticity of hMSC is a prerequisite for engineering functional and large scale cardiac tissue integration.
For more information, please see Cardiovascular Surgery and Biophysics Research Laboratory website.
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