Although heart failure is a leading cause of morbidity and mortality, the treatments of cardiac diseases associated with heart failure are inadequate. Understanding the molecular mechanisms promoting the transition of cardiac hypertrophy to heart failure will facilitate discovering new therapies for heart diseases. TRIB3 protein plays important roles in various diseases but its function in the heart is largely unknown. Our preliminary results indicated that TRIB3 protein expression is promoted in pressure overloaded mice hearts and its deletion attenuates cardiac hypertrophy. Our hypothesis is that TRIB3 is a novel protein that mediates progression of pathologic hypertrophy to heart failure by interacting with essential molecular pathways leading to cardiac dysfunction. Our hypothesis will be investigated by carrying out three aims to assess: 1) the role of TRIB3 deletion in attenuating hypertrophic response to pressure overload as well as to determine the role of TRIB3 in transition from pathologic hypertrophy to heart failure. 2) the role of TRIB3 in regulating MAPK pathway as a hallmark mechanism that regulates cardiac hypertrophy and failure. 3) the role of TRIB3 in modulating the mitochondrial fission machinery associated with pathologic hypertrophy. Progression of pathologic myocardial hypertrophy to heart failure will be assessed by using WT (control) and TRIB3 Knockout mice subjected to Transverse Aortic Constriction or sham operations. Mechanistic studies will be performed in vitro using neonatal rat cardiomyocytes. The candidate will be mentored by Dr. Douglas E Vaughan, a recognized pioneer in translational research of cardiovascular diseases. The primary goal of this AHA Career Development Award application is to provide the training and expertise that will allow Dr. Abdelwahid to transition from the mentored stage into his own research program as an independent investigator. The Award will allow him to gain multidisciplinary in-depth training in: 1) genetic modeling of heart hypertrophy and failure; 2) dissecting key signaling pathways in progression of hypertrophy to heart failure; 3) advancing his expertise in mitochondrial dynamic analyses in cardiac system; 4) improving his professional skills such as leading a multidisciplinary scientific team, managing his own laboratory, supervising others, writing grants, network building, advancement to promotion, writing skills, effective presentations and leadership.
|Effective start/end date||4/1/19 → 4/2/19|
- American Heart Association (19CDA34760076)