A5024970293- Ion Channels and Receptors
- Ion channel regulation and function
- Neurobiology and Insect Physiology Research
- Angiogenesis and VEGF in Cancer
- Muscle Physiology and Disorders
- Cardiac electrophysiology and arrhythmias
- Cell Adhesion Molecules Research
- Respiratory and Cough-Related Research
- Ubiquitin and proteasome pathways
- Congenital heart defects research
- Lung Cancer Treatments and Mutations
- Coronary Interventions and Diagnostics
- Connexins and lens biology
- Blood properties and coagulation
- Asthma and respiratory diseases
- Postharvest Quality and Shelf Life Management
- Intraocular Surgery and Lenses
- interferon and immune responses
- Atherosclerosis and Cardiovascular Diseases
- Chemical and Physical Studies
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- NF-κB Signaling Pathways
- Fibroblast Growth Factor Research
- Neuroscience and Neuropharmacology Research
- Magnesium in Health and Disease
Duke University
2013-2024
Duke Medical Center
2008-2023
Duke University Hospital
2008-2018
King's College London
2016
University of Oklahoma Health Sciences Center
2009
National Institute of Environmental Health Sciences
2009
The University of Texas Southwestern Medical Center
2004
Yonsei University
2004
National Heart Lung and Blood Institute
1995-2000
National Institutes of Health
1995-2000
We have shown that the angiogenic peptides basic fibroblast growth factor (bFGF) and vascular endothelial (VEGF) enhance canine coronary collateral development when administered for > or = 4 weeks. bFGF, a pluripotent mitogen of mesodermally derived cells, could theoretically exacerbate neointimal smooth muscle cell hyperplasia, fundamental component atherosclerosis. VEGF, an cell-specific permeability factor, deleterious effects related to hyperpermeability. The present investigation had...
Recently we reported that intracoronary administration of basic fibroblast growth factor (bFGF), a potent angiogenic peptide, increases collateral blood flow in dogs subjected to progressive left circumflex coronary artery (LCx) occlusion. The aim the present study was examine effect systemically administered bFGF on and assess its pharmacokinetics potential side effects.Forty-seven were ameroid-induced occlusion LCx, an intervention known induce development vessels. In phase I...
Rationale: Cardiac muscle adapts to increase workload by altering cardiomyocyte size and function resulting in cardiac hypertrophy. G protein–coupled receptor signaling is known govern the hypertrophic response through regulation of ion channel activity downstream failing cardiomyocytes. Objective: Transient potential canonical (TRPC) channels are operated previously implicated Our objective this study better understand how TRPC influence calcium signaling. Methods Results: Here, we used...
The G protein-coupled receptor kinases (GRKs) and beta-arrestins, families of molecules essential to the desensitization protein-dependent signaling via seven-transmembrane receptors (7TMRs), have been recently shown also transduce protein-independent signals from receptors. However, physiologic consequences this protein-independent, GRK/beta-arrestin-dependent are largely unknown. Here, we establish that GRK/beta-arrestin-mediated signal transduction angiotensin II (ANG) type 1A (AT(1A)R)...
We have shown that basic fibroblast growth factor (bFGF/FGF-2) enhances myocardial collateral development in a canine model of progressive coronary occlusion when delivered via the left atrial or intracoronary routes; however, we found intravenous bFGF ineffective same model. Data on fate and efficacy are limited. hypothesized first pass lung uptake might limit availability after injection. postulated delivery through distal port wedged Swan Ganz catheter circumvent this problem by...
Skeletal muscle adapts to different patterns of motor nerve activity by alterations in gene expression that match specialized properties contraction, metabolism, and mass changing work demands (muscle plasticity). Calcineurin, a calcium/calmodulin-dependent, serine–threonine protein phosphatase, has been shown control programs skeletal muscles, as other cell types, through the transcription factor nuclear activated T cells (NFAT). This study provides evidence function NFAT transcriptional...
Transient receptor potential (TRP) channels are nonselective cation channels, several of which expressed in striated muscle. Because the scaffolding protein Homer 1 has been implicated TRP channel regulation, we hypothesized that proteins play a significant role skeletal muscle function. Mice lacking exhibited myopathy characterized by decreased fiber cross-sectional area and force generation. knockout myotubes displayed increased basal current density spontaneous influx. This influx was...
BACKGROUND Crizotinib is used for the treatment of advanced anaplastic lymphoma kinase ( ALK )‐rearranged nonsmall cell lung cancer (NSCLC). Sinus bradycardia (SB) a side effect listed in its package insert. We investigated frequency and timing SB, patient characteristics associated with SB during crizotinib treatment, potential correlation between heart rate (HR) changes clinical response to crizotinib. METHODS A retrospective chart review was conducted characteristics, patients treatment....
Cardiac pacemaking is governed by specialized cardiomyocytes located in the sinoatrial node (SAN). SAN cells (SANCs) integrate voltage-gated currents from channels on membrane surface (membrane clock) with rhythmic Ca(2+) release internal stores (Ca(2+) to adjust heart rate meet hemodynamic demand. Here, we report that stromal interaction molecule 1 (STIM1) and Orai1 channels, key components of store-operated entry, are selectively expressed SANCs. Cardiac-specific deletion STIM1 mice...
Objective— Signaling that activates NFκB (nuclear factor κB) in smooth muscle cells (SMCs) is integral to atherosclerosis and involves reversible ubiquitination proteins downstream of proatherogenic receptors. Deubiquitination these mediated by USP20 (ubiquitin-specific protease 20), among other deubiquitinases. We sought determine whether activity SMCs decreases atherosclerosis. Approach Results— To address this question, we used male Ldlr −/− mice without (control) or with SMC-specific...
Excitation-contraction (EC) coupling in striated muscles is mediated by the cardiac or skeletal muscle isoform of voltage-dependent L-type Ca(2+) channel (Ca(v)1.2 and Ca(v)1.1, respectively) that senses a depolarization cell membrane, response, activates its corresponding intracellular release channel/ryanodine receptor (RyR) to stored Ca(2+), thereby initiating contraction. Specifically, following membrane depolarization, Ca(v)1.2 RyR (RyR2) through an influx extracellular Ca(2+). In...
Ryanodine receptors (RyRs), intracellular calcium release channels essential for skeletal and cardiac muscle contraction, are also expressed in various types of smooth cells. In particular, recent studies have suggested that airway cells (ASMCs) provoked by spasmogens, stored the isoform RyR (RyR2) contributes to response leads constriction (bronchoconstriction). Here we report mouse ASMCs express brain isoforms RyRs (RyR1 RyR3, respectively). these cells, RyR1 is localized periphery near...
Alveolar septation increases gas-exchange surface area and requires coordinated cytoskeletal rearrangement in lung fibroblasts (LFs) to balance the demands of contraction cell migration. We hypothesized that DBN (drebrin), a modulator actin cytoskeleton neuronal dendrites, regulates remodeling LF cytoskeleton. Using mice bearing transgelin-Cre–targeted deletion Dbn pulmonary pericytes, we examined alterations alveolar septal outgrowth, spreading migration, actomyosin function. The number...
During muscle development, the sarco/endoplasmic reticulum (SR/ER) undergoes remodeling to establish a specialized internal Ca(2+) store for contraction. We hypothesized that operated entry (SOCE) is required fill stores and is, therefore, critical creating mature SR/ER. Stromal interaction molecule 1 (STIM1) functions as sensor of content an activator SOCE channels. Myocytes lacking STIM1 display reduced SR altered expression key proteins. Sarcolipin (SLN), inhibitor calcium pump, was...
The oncoprotein Mdm2 is a RING domain-containing E3 ubiquitin ligase that ubiquitinates G protein-coupled receptor kinase 2 (GRK2) and β-arrestin2, thereby regulating β-adrenergic (βAR) signaling endocytosis. Previous studies showed cardiac expression critical for controlling p53-dependent apoptosis during early embryonic development, but the role of in developed adult heart unknown. We aimed to identify if affects βAR function mice. Using Mdm2/p53-KO mice, which survive 9-12 months, we...
Sinus bradycardia is frequently observed in patients treated with crizotinib, a receptor tyrosine kinase inhibitor used for the treatment of anaplastic lymphoma (ALK)-rearranged non-small cell lung cancer (NSCLC). We investigated whether crizotinib could influence heart rate (HR) through direct cardiac effects.The effect on HR was studied using ECG analysis Langendorff-perfused mouse hearts. The whole-cell patch clamp technique to measure effects hyperpolarization-activated funny current,...