Contact
Office: 305-243-2908
Roles
Professor of Molecular and Cellular Pharmacology
Sylvester Comprehensive Cancer Center
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Biography
Dr. Szczesna-Cordary received her Master of Science degree in Biophysical Chemistry from the University of Warsaw in Poland. In 1983, she initiated her research on skeletal muscle contraction and myosin regulatory light chain phosphorylation under the tutelage of Prof. Irena Kakol at the Nencki Institute of Experimental Biology of the Polish Academy of Sciences in Warsaw. During her PhD thesis work, she completed two fellowships in muscle physiology, biochemistry, and biophysics, first at the Institute of Cytology in St. Petersburg, Russia, and then at the Institute of Molecular Biology, Austrian Academy of Sciences, Salzburg, Austria. She received her PhD degree in Natural Sciences in 1989 from the Nencki Institute, Polish Academy of Sciences.
In 1990, she secured a postdoctoral position in Shervin Lehrer's laboratory at the Boston Biomedical Institute, Boston, USA, where she studied muscle tropomyosin using fluorescence spectroscopy. In 1993, she utilized EPR to study the steric blocking mechanism at Florida State University, Institute of Molecular Biophysics, Tallahassee, FL. In 1994, she was recruited by Dr. James D. Potter to study the structure-function relationships of sarcomeric proteins, specifically muscle troponin T, I, and C, at the Department of Molecular and Cellular Pharmacology (MCP), University of Miami Miller School of Medicine, Miami, FL.
She advanced through several academic positions at the University of Miami: Sr. Postdoctoral Associate (1994-1995), Instructor (1995-1997), Research Assistant Professor (1997-2003), Research Associate Professor (2003-2006), Associate Professor (tenure track, 2006-2012), tenured (June 2010), and Professor with tenure in Molecular and Cellular Pharmacology.
Dr. Szczesna-Cordary's research has been continually supported by grants from the National Institutes of Health (NIH) and the American Heart Association. Between 2005 and 2018, she served as a member on two NIH study sections (CCHF and SMEP). She has published over 100 scientific papers and serves as an editor and reviewer for prestigious scientific journals. -
Education & Training
Education
Post Graduate Training
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Teaching Interests
Dr. Szczesna-Cordary’s teaching interests are in the area of molecular, and cellular mechanisms controlling the physiology of cardiac function with a focus on the regulation of the molecular motors of the heart. Specific objectives include 1) the molecular mechanisms by which thick and thin filament proteins turn on and modulate the activity of heart muscle cells, 2) alterations in this mechanism that occur during cardiac pathologies including genetic cardiomyopathies, and 3) pharmacological or small molecule manipulation of the molecular signaling process by agents acting directly or indirectly on the myofilament response to Ca2+. The approaches have made use of a broad array of technologies including 1) mutagenesis, expression, purification, and in vitro reconstitution of myosin subunits (myosin light chains) combined with measurements of regulation of force and energy coupling, 2) transgenesis using overexpression of myofilament proteins including myosin RLC, and ELC, 3) in situ and in vitro determination of cardiac function employing isolated cardiomyocytes (muscle fibers), and in situ heart function. -
Research Interests
The general research interests of my laboratory focus on striated (skeletal and cardiac) muscle contraction and the mechanisms that control force generation in muscle and work in parallel with the Ca2+-dependent regulatory system, tropomyosin (Tm), and troponin (Tn). Calcium-binding to the thin filament is the major element controlling active force in muscle, but other processes regulate contractile force and sarcomere shortening. In particular, we are interested in the regulation of contraction by the myosin regulatory (RLC) and essential (ELC) light chains encoded by MYL2 and MYL3 genes, respectively. Myosin-II is an actin-dependent molecular motor that uses chemical energy derived from Mg·ATP hydrolysis to produce mechanical work and filament movement. Both myosin light chains (RLC and ELC) constitute an essential part of the myosin molecule by supporting the neck region (lever arm) of the myosin head (cross-bridge) but they also contribute to the regulation of the acto-myosin ATPase cycle and the power stroke. We hypothesize that both myosin light chains interact with the myosin heavy chain (MHC) to provide structural stability to the myosin lever arm and support its function in propagating the conformational changes from the motor domain to the myosin backbone and in the transmission of external loads to the myosin active site.
The importance of both myosin light chains has been highlighted by the identification of about 30 missense mutations in MYL2 and MYL3 genes in patients suffering from familial Hypertrophic (HCM), Dilated (DCM), or Restrictive (RCM) Cardiomyopathy.
Using transgenic mouse models of human HCM, DCM, or RCM, the Szczesna-Cordary Lab is studying the biomechanics of heart muscle from the organ down to the molecular level employing a combination of physiological, hemodynamic, and molecular approaches. The research work has predominantly focused on identifying novel mechanisms and validating new targets and/or treatments to battle cardiomyopathy and heart failure. These studies have been a very rich source of information for a variety of aspects of myosin light chain-induced cardiomyopathy providing mechanistic insight into this highly detrimental cardiac disease. We have already reached the next step and are making our findings applicable in translational research experiments developing target-specific therapeutic approaches. -
Publications
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