A5103150543- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Mitochondrial Function and Pathology
- Neuroscience and Neural Engineering
- ATP Synthase and ATPases Research
- Neuroscience and Neuropharmacology Research
- Adipose Tissue and Metabolism
- Advanced Fluorescence Microscopy Techniques
- Receptor Mechanisms and Signaling
- Cardiac Arrhythmias and Treatments
- Cardiac Ischemia and Reperfusion
- Nitric Oxide and Endothelin Effects
- Cardiomyopathy and Myosin Studies
- Protein Structure and Dynamics
- Electron Spin Resonance Studies
- Fuel Cells and Related Materials
- Analytical Chemistry and Sensors
- Gene Regulatory Network Analysis
- ECG Monitoring and Analysis
- 14-3-3 protein interactions
- Microtubule and mitosis dynamics
- Cardiovascular Effects of Exercise
- Cellular transport and secretion
- Metabolism, Diabetes, and Cancer
- Viral Infectious Diseases and Gene Expression in Insects
University of Maryland, Baltimore
2011-2020
University of Baltimore
2013-2017
George Mason University
2009-2014
Université Paris Cité
2012
Max Planck Institute for Dynamics and Self-Organization
2012
Cornell University
2012
Max Planck Institute for Biophysical Chemistry
2012
William & Mary
2003-2008
Williams (United States)
2003-2008
Rationale: Transverse tubules (TTs) couple electric surface signals to remote intracellular Ca 2+ release units (CRUs). Diffraction-limited imaging studies have proposed loss of TT components as disease mechanism in heart failure (HF). Objectives: Objectives were develop quantitative super-resolution strategies for live-cell membranes intact cardiomyocytes and show that structures are progressively remodeled during HF development, causing early CRU dysfunction. Methods Results: Using...
The canonical atrial myocyte (AM) is characterized by sparse transverse tubule (TT) invaginations and slow intracellular Ca2+ propagation but exhibits rapid contractile activation that susceptible to loss of function during hypertrophic remodeling. Here, we have identified a membrane structure Ca2+-signaling complex may enhance the speed contraction independently phospholamban regulation. This axial couplon was observed in human mouse atria composed voluminous tubules (ATs) with extensive...
Atrial fibrillation (AF) is characterized by sustained high atrial activation rates and arrhythmogenic cellular Ca2+ signaling instability; however, it not clear how a rate instability may be related. Here, we subcellular after 5 days of in rabbit model. While some changes were similar to those persistent AF, identified distinct pattern stabilized signaling. sparks, waves, sarcoplasmic reticulum (SR) leak, SR content largely unaltered. Based on computational analysis, these findings...
Stable calcium-induced calcium release (CICR) is critical for maintaining normal cellular contraction during cardiac excitation-contraction coupling. The fundamental element of CICR in the heart (Ca2+) spark, which arises from a cluster ryanodine receptors (RyR). Opening these RyR clusters triggered to produce local, regenerative Ca2+ sarcoplasmic reticulum (SR). leak out SR an important process management, and it critically influenced by spark fidelity, i.e., probability that spontaneous...
Abstract The sympathetic nervous system is essential for maintenance of cardiac function via activation post-junctional adrenergic receptors. Prolonged receptor activation, however, has deleterious long-term effects leading to hypertrophy and the development heart failure. Here we investigate effect chronic receptors on excitation-contraction coupling (ECC) in ventricular cardiomyocytes from a previously characterized mouse model hyperactivity, which are genetically deficient adrenoceptor...
Key points Our group previously discovered and characterized the microtubule mechanotransduction pathway linking diastolic stretch to NADPH oxidase 2‐derived reactive oxygen species signals that regulate calcium sparks influx pathways. Here we used focused experimental tests constrain expand our existing computational models of signalling in heart. Mechanistic quantitative modelling revealed new insights disease including: changes network density properties, elevated NOX2 expression, altered...
This work explores dynamical couplings between global enzymatic fluctuation patterns and the catalytic fitness of a model enzyme system. A genetic algorithm drives evolution population molecules toward greater by modifying via recombination mutation events interaction strengths subunits. We've identified, through combination molecular dynamics simulation an approximate normal-mode analysis, two features that are tuned for increased efficacy throughout evolutionary process. First, average...