A5006439084- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Erythrocyte Function and Pathophysiology
- Cardiac Fibrosis and Remodeling
- Receptor Mechanisms and Signaling
- Cardiomyopathy and Myosin Studies
- Pancreatic function and diabetes
- Neuroscience and Neural Engineering
- Signaling Pathways in Disease
- Diabetes and associated disorders
- Celiac Disease Research and Management
- Mindfulness and Compassion Interventions
- Central Venous Catheters and Hemodialysis
- Peripheral Artery Disease Management
- Vascular anomalies and interventions
- Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Cardiac and Coronary Surgery Techniques
- Long-Term Effects of COVID-19
- Cell Image Analysis Techniques
- Cardiac Arrhythmias and Treatments
- NF-κB Signaling Pathways
- Mechanical Circulatory Support Devices
- Metabolism, Diabetes, and Cancer
- Galectins and Cancer Biology
- Gene Regulatory Network Analysis
The Ohio State University Wexner Medical Center
2014-2021
The Ohio State University
2014-2020
Masonic Medical Research Laboratory
2020
Lung Institute
2015
Howard Hughes Medical Institute
2014
Duke University Hospital
2014
Duke Medical Center
2014
National University of Singapore
2013
Rationale: Na v 1.5 ( SCN5A ) is the primary cardiac voltage-gated channel. critical for excitability and conduction, human mutations cause sinus node dysfunction, atrial fibrillation, conductional abnormalities, ventricular arrhythmias. Further, defects in regulation are linked with malignant arrhythmias associated heart failure. Consequently, therapies to target select properties have remained at forefront of cardiovascular medicine. However, despite years investigation, fundamental...
Voltage-gated Na(+) channels (Nav) are essential for myocyte membrane excitability and cardiac function. Nav current (INa) is a large-amplitude, short-duration spike generated by rapid channel activation followed immediately inactivation. However, even under normal conditions, small late component of INa (INa,L) persists because incomplete/failed inactivation subpopulation channels. Notably, INa,L directly linked with both congenital acquired disease states. The multifunctional...
Two-pore K(+) channels have emerged as potential targets to selectively regulate cardiac cell membrane excitability; however, lack of specific inhibitors and relevant animal models has impeded the effort understand role 2-pore in heart their a therapeutic target. The objective this study was determine mechanosensitive channel family member TREK-1 control excitability.Cardiac-specific TREK-1-deficient mice (αMHC-Kcnk(f/f)) were generated found prevalent sinoatrial phenotype characterized by...
Cardiac function depends on the highly regulated and co-ordinate activity of a large ensemble potassium channels that control myocyte repolarization. While voltage-gated K+ have been well characterized in heart, much less is known about regulation and/or targeting two-pore channel (K2P) family members, despite their potential importance modulation heart function. Here, we report novel molecular pathway for membrane TREK-1, mechano-sensitive K2P by environmental physical factors including...
Although triggered arrhythmias including catecholaminergic polymorphic ventricular tachycardia (CPVT) are often caused by increased levels of circulating catecholamines, the mechanistic link between β-adrenergic receptor (AR) stimulation and subcellular/molecular arrhythmogenic trigger(s) is unclear. Here, we systematically investigated subcellular molecular consequences β-AR in promotion catecholamine-induced cardiac arrhythmias. Using mouse models calsequestrin-associated CPVT, demonstrate...
Heart failure (HF) remains a major source of morbidity and mortality in the US. The multifunctional Ca2+/calmodulin-dependent kinase II (CaMKII) has emerged as critical regulator cardiac hypertrophy failure, although mechanisms remain unclear. Previous studies have established that cytoskeletal protein βIV-spectrin coordinates local CaMKII signaling. Here, we sought to determine role spectrin-CaMKII complex maladaptive remodeling HF. Chronic pressure overload (6 weeks transaortic...
Cardiac calsequestrin (CASQ2) and histidine-rich Ca-binding protein (HRC) are sarcoplasmic reticulum (SR) proteins that regulate SR Ca release in mammalian heart. Deletion of either CASQ2 or HRC results relatively mild phenotypes characterized by preserved cardiac structure function, although knockout (KO), Cnull, shows increased arrhythmia burden under conditions catecholaminergic stress. We hypothesized given the apparent overlap functions HRC, simultaneous ablation both would deteriorate...
Image processing and quantification is a routine important task across disciplines in biomedical research. Understanding the effects of disease on tissue organ level often requires use images, however process interpreting those images into data which can be tested for significance time intensive, tedious prone to inaccuracy or bias. When working within resource constraints, these different issues present trade-off between invested analysis accuracy. To address issues, we two novel open...
Increased fibrosis is a characteristic remodeling response to biomechanical and neurohumoral stress determinant of cardiac mechanical electrical dysfunction in disease. Stress-induced activation fibroblasts (CFs) critical step the fibrotic response, although precise sequence events underlying these cells vivo remain unclear. Here, we tested hypothesis that βIV-spectrin/STAT3 complex essential for maintenance quiescent phenotype (basal nonactivated state) CFs. We reported increased fibrosis,...
In the heart, pathways that transduce extracellular environmental cues (e.g. mechanical force, inflammatory stress) into electrical and/or chemical signals at cellular level are critical for organ-level response to chronic biomechanical/neurohumoral stress. Specifically, a diverse array of membrane-bound receptors and stretch-activated proteins converge on network intracellular signaling cascades control gene expression, protein translation, degradation regulation. These reprogramming events...
Ankyrin polypeptides are intracellular proteins responsible for targeting cardiac membrane proteins. Here, the authors demonstrate that ankyrin-G plays an unexpected role in normal compensatory physiological remodeling response to myocardial stress and aging; implicate disruption of human heart failure. Mechanistically, illustrate serves as a key nodal protein required myofilament integration with intercalated disc. Their data define novel vivo mechanistic roles ankyrin-G, necessary under...
Fibrosis is a pronounced feature of heart disease and the result dysregulated activation resident cardiac fibroblasts (CFs). Recent work identified stress-induced degradation cytoskeletal protein βIV-spectrin as an important step in CF fibrosis. Furthermore, loss was found to depend on Ca2+/calmodulin-dependent kinase II (CaMKII). Therefore, we sought determine mechanism for CaMKII-dependent regulation activity. Computational screening MS revealed critical serine residue (S2250 mouse S2254...
Opioid use disorder (OUD) is widely prevalent in the United States and there are high levels of comorbidity between OUD mental illnesses, such as depression, anxiety, posttraumatic stress disorder. Psychotherapy, addition to medication-assisted therapy, considered important components long-term treatment. Sudarshan Kriya Yoga (SKY) a breathing-based mind–body intervention that has been demonstrated have multiple physiological psychological benefits. In current study, participants ( N = 8)...
Our immune system constantly samples peptides found inside the body as a means to detect foreign pathogens, infected cells, and tumorous cells. T which carry out critical task of distinguishing self from nonself peptides, can only survey that are presented by major histocompatibility complex protein. We investigated how secondary structure peptide, namely, polyproline II helix content, influences binding. synthesized 12 analogues wheat gluten derived α-I-gliadin peptide tested their binding...
Increased fibrosis is associated with cardiac dysfunction and arrhythmias. Activation of quiescent fibroblasts (CFs) occurs in response to injury although the underlying mechanistic pathways remain unclear. The cytoskeletal protein β IV -spectrin has been shown control targeting activity multifunctional transcription factor Signal Transducer Activator Transcription 3 (STAT3) for maladaptive remodeling. mechanism linking spectrin altered STAT3 signaling, fibrosis, function remains unknown....