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The Washington Research Foundation Fellowship
Kate Buckley, Bioengineering - 2009-10 WRFF
Kate Buckley’s strong interest in cardiac repair began when she was introduced to the field by her mentor, Dr. Mike Regnier. Kate has been passionate about research since she arrived in the lab in the fall of her freshman year, and is motivated by a continuing interest in the therapies she investigates and the constant need for translational research that aims to address current health problems. Kate is particularly interested in creating genetic and cellular therapies in cardiac muscle that could be applied to different forms of heart disease. The Washington Research Foundation Fellowship has given her the opportunity to explore a novel research question that will allow her to delve deeper into the exciting opportunities that research offers.
Mentor: Michael Regnier, Bioengineering
Project Title: Myofilament Targeted Genetic Therapy as a Treatement for Heart Attack: Studies in the Whole Organ
Abstract: Heart disease is currently the leading cause of death in the United States, killing over half a million people every year. One of the most common forms of heart disease is the heart attack (cardiac infarction). After a cardiac infarction occurs, the heart undergoes an extensive remodeling process in which normal cardiovascular function is disrupted. Gene-based therapies offer an alternative to current treatments as a method to improve cardiac function post-cardiac infarction. The genetic therapy L48Q in cardiac Troponin C offers potential as a therapeutic tool by enhancing Ca2+ binding within cardiac muscle tissue upon contraction, which may halt or even reverse the deleterious remodeling process by altering contractile properties within the myofilament. Current studies in virally tranfected rat cardiomyocytes have shown that that cTnC L48Q enhances contractile properties by increasing the amplitude of contraction in normal cells by 50% and increasing the rate of contraction by 55%, but the effect of this genetic therapy in the whole organ is unknown. To study the action of cTnC L48Q in the whole heart in the normal and infarcted hearts, both in vivo and in vitro methods will be utilized. Functional changes in vivo will be investigated using echocardiography to obtain measurements of ventricular diameter, ejection fraction, and fractional shortening. In vitro studies will be conducted using a modified Langendorff isolated working heart preparation to measure the preload responsiveness of the heart and the adrenergic responsiveness of normal and infarcted hearts after transfection with cTnC L48Q. Additionally, functional measurements in demembranated muscle strips will investigate contractile changes. The in vivo and the in vitro studies of the whole organ will provide a comprehensive functional assessment of the genetic therapy in the whole organ, providing essential information about the future feasibility of this therapeutic for use as a clinical treatment for heart disease.