A5016255536- Connexins and lens biology
- Cardiac electrophysiology and arrhythmias
- Congenital heart defects research
- Ion channel regulation and function
- Heat shock proteins research
- Cardiomyopathy and Myosin Studies
- Nicotinic Acetylcholine Receptors Study
- Cardiovascular Effects of Exercise
- Cardiac Fibrosis and Remodeling
- Wound Healing and Treatments
- Neuroscience and Neural Engineering
- Tissue Engineering and Regenerative Medicine
- Cardiac Arrhythmias and Treatments
- RNA Interference and Gene Delivery
- Extracellular vesicles in disease
- Nitric Oxide and Endothelin Effects
- Molecular Biology Techniques and Applications
- RNA and protein synthesis mechanisms
- Yersinia bacterium, plague, ectoparasites research
- Coronary Artery Anomalies
- Barrier Structure and Function Studies
- Cancer-related molecular mechanisms research
- S100 Proteins and Annexins
- Dermatologic Treatments and Research
- Electrospun Nanofibers in Biomedical Applications
Carilion Roanoke Memorial Hospital
2016-2025
Virginia Tech
2016-2025
Carilion Clinic
2016-2025
Biomedical Research Institute
2019-2025
Virginia Tech - Wake Forest University School of Biomedical Engineering & Sciences
2014-2023
Center for Neuroscience and Regenerative Medicine
2019
Mechanics' Institute
2018
Medical University of South Carolina
2004-2013
Clemson University
2006-2013
College of Charleston
2011
The vascular smooth muscle cells of coronary arteries are distinguished from those the proximal aorta by a number structural and functional criteria which may include an increased propensity for atherosclerotic transformation. At present, source this variation between subpopulations is uncertain. Whilst thought to be derived neural crest, origin remains uncharacterized. We have previously shown that precursors vasculature enter tubular heart on same day as epicardial mantle starts envelop...
Abstract —The epicardium and dorsal mesocardium are known to be the source of structures that form wall coronary vessels. Because mouse knockout studies have shown proper epicardial formation is also essential for myocardial development, we studied in detail migration differentiation epicardium-derived cells (EPDCs) within developing heart. We constructed chicken-quail chimeras by grafting quail organ, including a piece primordial liver, at essentially stages 16 17. The embryos were 25 43....
Myocardial infarction is a prevalent major cardiovascular event that arises from myocardial ischemia with or without reperfusion, and basic translational research needed to better understand its underlying mechanisms consequences for cardiac structure function. Ischemia underlies broad range of clinical scenarios ranging angina hibernation permanent occlusion, while reperfusion mandatory salvage ischemic injury, also inflicts injury on own. In this consensus statement, we present...
Regulation of gap junction (GJ) organization is critical for proper function excitable tissues such as heart and brain, yet mechanisms that govern the dynamic patterning GJs remain poorly defined. Here, we show zonula occludens (ZO)-1 localizes preferentially to periphery connexin43 (Cx43) GJ plaques. Blockade PDS95/dlg/ZO-1 (PDZ)-mediated interaction between ZO-1 Cx43, by genetic tagging Cx43 or a membrane-permeable peptide inhibitor contains PDZ-binding domain, led reduction peripherally...
Connexin 43 (Cx43) is a gap junction (GJ) protein widely expressed in mammalian tissues that mediates cell-to-cell coupling. Intercellular channels comprising GJ aggregates form from docking of paired connexons, with one each contributed by apposing cells. Zonula occludens-1 (ZO-1) binds the carboxy terminus Cx43, and we have previously shown inhibition Cx43/ZO-1 interaction increases size 48 h. Here demonstrated aggregation occur within 2 h (∼Cx43 half-life) following disruption Cx43/ZO-1....
Electrical coupling between heart muscle cells is mediated by specialised regions of sarcolemmal interaction termed gap junctions. In previous work, we have demonstrated that connexin42, a recently identified gap-junctional protein, present in the conduction tissues avian heart. study, spatial distribution mammalian homologue this connexin40, was examined using immunofluorescence, confocal scanning laser microscopy and quantitative digital image analysis order to determine whether parallel...
Heterozygous mutations of the cardiac transcription factor Nkx2-5 cause atrioventricular conduction defects in humans by unknown mechanisms. We show KO mice that number cells system is directly related to gene dosage. Null mutant embryos appear lack primordium node. In haploinsufficiency, has half normal cells. addition, an entire population connexin40(-)/connexin45(+) missing node heterozygous mice. Specific functional associated with loss function can be attributed hypoplastic development...
Nonuniformity in the spatial patterning of gap junctions between heart muscle cells is now recognized as an important determinant electromechanical function working myocardium. Breakdown normal geometry electrical intercellular connectivity diseased myocardium correlates with reentry, arrhythmia, and conduction disturbance. The developmental mechanism(s) that determines this precise order junction organization at present unknown. To examine question, we have used immunoelectron...
ABSTRACT Transgenic mice were generated containing a cytomegaloviral promoter driven construct (CMV43) expressing the gap junction polylpeptide connexin 43. RNA and protein analysis confirmed that transgene was being expressed. In situ hybridization of embryo sections revealed expression targeted to dorsal neural tube in subpopulations crest cells. This pattern identical seen transgenic harboring other constructs by (Kothary, R., Barton, S. C., Franz, T., Norris, M. L., Hettle, Surani, A. H....
ABSTRACT The rhythmic contraction of the vertebrate heart is dependent on organized propagation electrical excitation through cardiac conduction system. Because both muscleand neuron-specific genes are co-expressed in cells forming myocardial tissues, two origins, myogenic and neural, have been suggested for this specialized tissue. Using replication-defective retroviruses, encoding recombinant β-galactosidase (β-gal), we analyzed cell lineage Purkinje fibers (i.e., peripheral elements...
Zebrafish and Xenopus have become popular model organisms for studying vertebrate development of many organ systems, including the heart. However, it is not clear whether single ventricular hearts these species possess any equivalent specialized conduction system found in higher vertebrates. Isolated adult zebrafish ( Danio rerio) African toads laevis) were stained with voltage-sensitive dye optically mapped spontaneous paced rhythms followed by histological examination focusing on...
The His-Purkinje system (HPS) is a network of conduction cells responsible for coordinating the contraction ventricles. Earlier studies using bipolar electrodes indicated that functional maturation HPS in chick embryo marked by topological shift sequence activation ventricle. Namely, at around completion septation, an immature base-to-apex ventricular was reported to convert apex-to-base pattern characteristic mature heart. Previously, we have proposed hemodynamics and/or mechanical...
Rationale: Remodeling of connexin (Cx)43 gap junctions (GJs) is linked to ventricular arrhythmia. Objectives: A peptide mimetic the carboxyl terminal (CT) Cx43, incorporating a postsynaptic density-95/ d isks-large/ Z O-1 (PDZ)-binding domain, reduces Cx43/ZO-1 interaction and GJ size remodeling in vitro. Here, we determined: (1) whether Cx43-CT αCT1 altered following left (LV) injury vivo; (2) affected arrhythmic propensity; (3) mechanism effects on arrhythmogenicity remodeling. Methods...
Resistance of glioblastoma (GBM) to the front-line chemotherapeutic agent temozolomide (TMZ) continues challenge GBM treatment efforts. The repair TMZ-induced DNA damage by O-6-methylguanine-DNA methyltransferase (MGMT) confers one mechanism TMZ resistance. Paradoxically, MGMT-deficient patients survive longer despite still developing resistance TMZ. Recent studies indicate that gap junction protein connexin 43 (Cx43) renders cells resistant through its carboxyl terminus (CT). In this study,...
It has long been held that electrical excitation spreads from cell-to-cell in the heart via low resistance gap junctions (GJ). However, it also proposed myocytes could interact by non-GJ-mediated "ephaptic" mechanisms, facilitating propagation of action potentials tandem with direct GJ-mediated coupling. We sought evidence such mechanisms contribute to cardiac conduction. Using super-resolution microscopy, we demonstrate Nav1.5 is localized within 200 nm GJ plaque (a region termed...
Computational modeling indicates that cardiac conduction may involve ephaptic coupling - intercellular communication involving electrochemical signaling across narrow extracellular clefts between cardiomyocytes. We hypothesized β1(SCN1B) -mediated adhesion scaffolds trans-activating NaV1.5 (SCN5A) channels within (<30 nm) perinexal adjacent to gap junctions (GJs), facilitating coupling. Super-resolution imaging indicated preferential β1 localization at the perinexus, where it co-locates with...
The gap junction protein, connexin43 (Cx43), has critical roles in the inflammatory, edematous, and fibrotic processes following dermal injury during wound healing, is abnormally upregulated at epidermal margins of venous leg ulcers (VLUs). Targeting Cx43 with ACT1, a peptide mimetic carboxyl-terminus Cx43, accelerates fibroblast migration proliferation, reepithelialization. In prospective, multicenter clinical trial conducted India, adults chronic VLUs were randomized to treatment an ACT1...
BACKGROUND: Viral cardiac infection represents a significant clinical challenge encompassing several etiological agents, disease stages, complex presentation, and resulting lack of mechanistic understanding. Myocarditis is major cause sudden death in young adults, where current knowledge the field dominated by later phases pathological immune responses. However, little known regarding how can acutely induce an arrhythmogenic substrate before Adenovirus leading myocarditis, but due to species...
Abstract Extracellular vesicles (EVs) are widely investigated for their implications in cell-cell signaling, immune modulation, disease pathogenesis, cancer, regenerative medicine, and as a potential drug delivery vector. However, maintaining integrity bioactivity of EVs between Good Manufacturing Practice separation/filtration end-user application remains consistent bottleneck towards commercialization. Milk-derived extracellular (mEVs), separated from bovine milk, could provide relatively...