This proposal describes a five year training program to develop an academic career in Cardiology. The principal investigator has completed structured residency training in Medicine at Duke University Medical Center and is completing Cardiology fellowship training at the same institution. Now, he will expand upon his clinical and scientific skills through uniquely developed interdepartmental collaborations and mentoring. This program will develop a new field of study, namely the integration of Drosophila genetics and human cardiovascular disease to identify novel genes that cause dilated cardiomyopathy. Dr. Howard Rockman will mentor the principle investigator's scientific development. Dr. Rockman is a recognized leader in the field of receptor biology and the genetics of cardiomyopathy and heart failure. To enhance the training, the program will include the expertise of Dr. Joseph A. Izatt, Assistant Professor of Biomedical Engineering and Dr. Hubert Amrein, Assistant Professor in Molecular Genetics and Microbiology. In addition, a committee of highly-regarded medical scientists will provide scientific and career advice. Recent work in the laboratories of Drs. Rockman and Izatt has demonstrated that optical coherence tomography can accurately and rapidly detect normal and abnormal cardiac function in awake, adult Drosophila. This proposal hypothesizes that studies employing of Drosophila genetics can lead to the identification of genes causing human dilated cardiomyopathies.
The specific aims are to: 1) Investigate the biochemical and genetic mechanisms through which mutations in the decapentaplegic (dpp) / bone morphogenetic protein (BMP) signaling pathway lead to dilated cardiomyopathy in adult Drosophila. 2) Identify novel genes that cause cardiomyopathy through a genome-wide screen of adult Drosophila. 3) Investigate the genetic mechanisms that modify survival and cardiac function in adult Drosophila with dilated cardiomyopathy.
|Casad, Michelle E; Yu, Lin; Daniels, Joseph P et al. (2012) Deletion of Siah-interacting protein gene in Drosophila causes cardiomyopathy. Mol Genet Genomics 287:351-60|
|Wolf, Matthew J (2012) Modeling dilated cardiomyopathies in Drosophila. Trends Cardiovasc Med 22:55-61|
|Lin, Na; Badie, Nima; Yu, Lin et al. (2011) A method to measure myocardial calcium handling in adult Drosophila. Circ Res 108:1306-15|
|Wolf, Matthew J; Rockman, Howard A (2011) Drosophila, genetic screens, and cardiac function. Circ Res 109:794-806|
|Casad, Michelle E; Abraham, Dennis; Kim, Il-Man et al. (2011) Cardiomyopathy is associated with ribosomal protein gene haplo-insufficiency in Drosophila melanogaster. Genetics 189:861-70|
|Yu, Lin; Lee, Teresa; Lin, Na et al. (2010) Affecting Rhomboid-3 function causes a dilated heart in adult Drosophila. PLoS Genet 6:e1000969|
|Kim, Il-Man; Wolf, Matthew J; Rockman, Howard A (2010) Gene deletion screen for cardiomyopathy in adult Drosophila identifies a new notch ligand. Circ Res 106:1233-43|
|Kim, Il-Man; Wolf, Matthew J (2009) Serial examination of an inducible and reversible dilated cardiomyopathy in individual adult Drosophila. PLoS One 4:e7132|