A5018423651- Cardiomyopathy and Myosin Studies
- Cardiovascular Function and Risk Factors
- Cardiac electrophysiology and arrhythmias
- Cardiovascular Effects of Exercise
- Cardiac pacing and defibrillation studies
- Protein Tyrosine Phosphatases
- Ion channel regulation and function
- Viral Infections and Immunology Research
- Cardiac Imaging and Diagnostics
- Acute Myocardial Infarction Research
- Cardiac tumors and thrombi
- Lipoproteins and Cardiovascular Health
University of Arizona
2018-2024
BACKGROUND: Impaired left ventricular relaxation, high filling pressures, and dysregulation of Ca 2+ homeostasis are common findings contributing to diastolic dysfunction in hypertrophic cardiomyopathy (HCM). Studies have shown that impaired relaxation is an early observation the sarcomere-gene-positive preclinical HCM cohort, which suggests potential involvement myofilament regulators relaxation. A molecular-level understanding mechanism(s) at level lacking. We hypothesized...
In the heart, Ca/Calmodulin Kinase IIδ (CaMKIIδ) functions to maintain electromechanical and calcium homeostasis. Post-translational modifications (PTMs) of CaMKIIδ render its activity autonomous Ca/CaM. hypertrophic cardiomyopathy (HCM), increased levels are linked disease progression. We have shown that pathogenic role in HCM is mutation-specific: elevated cardiac troponin T (cTnT)-R92W mice, but not cTnT-R92L mice. These results pose a clinically relevant critical question: what trigger...
Anthracyclines are a key component in the management of pediatric cancers long recognized to carry significant risk dose-dependent cardiotoxicity. Despite advancements clinical management, considerable variation incidence cardiotoxicity persists across dosing regimens suggesting modifiers exist. Recently, changes splicing TNNT2, gene encoding cardiac troponin T (cTnT), were postulated contribute anthracycline cardiotoxicity, potentially providing direct link myofilament. Previous studies our...
ABSTRACT Background Impaired left ventricular relaxation, high filling pressures, and dysregulation of Ca 2+ homeostasis are common findings contributing to diastolic dysfunction in hypertrophic cardiomyopathy (HCM). Studies have shown that impaired relaxation is an early observation the sarcomere-gene-positive preclinical HCM cohort which suggests potential involvement myofilament regulators relaxation. Yet, a molecular level understanding mechanism(s) at lacking. We hypothesized...
Autophosphorylation of Calmodulin-Kinase IIδ (CaMKIIδ) at Thr-287 leads to autoactivation such that kinase activity is autonomous Ca 2+ /CaM. In the heart, CaMKIIδ functions regulate homeostasis by targeting handling proteins, including phospholamban (PLB). sarcomeric hypertrophic cardiomyopathy (HCM), disruption and aberrant has been linked disease progression. We have previously shown pathogenic role in HCM mutation-specific. Transgenic mice expressing mutation R92W cardiac troponin T...