A5081340005- Chromosomal and Genetic Variations
- Genomics and Chromatin Dynamics
- Microtubule and mitosis dynamics
- Retinal Development and Disorders
- DNA Repair Mechanisms
- Ion channel regulation and function
- Nicotinic Acetylcholine Receptors Study
- RNA modifications and cancer
- Neuroscience and Neuropharmacology Research
- Gene Regulatory Network Analysis
- Nuclear Structure and Function
- Photosynthetic Processes and Mechanisms
- Cardiomyopathy and Myosin Studies
- RNA and protein synthesis mechanisms
- CRISPR and Genetic Engineering
- Cardiac electrophysiology and arrhythmias
- RNA Research and Splicing
- Metabolism, Diabetes, and Cancer
- Advanced Fluorescence Microscopy Techniques
- Genomic variations and chromosomal abnormalities
- Atherosclerosis and Cardiovascular Diseases
- Advanced biosensing and bioanalysis techniques
- Cellular transport and secretion
- Muscle and Compartmental Disorders
- Plant Virus Research Studies
University of Pennsylvania
2009-2025
Children's Hospital of Philadelphia
2023
Penn Center for AIDS Research
2023
Consumer Healthcare Products Association
2023
Institute of Molecular Biology and Biophysics
2015
Interface (United States)
2009
Queen's University Belfast
2004-2007
University of Ulster
2004
Royal Victoria Hospital
2004
Activated platelets, which release platelet factor 4 (PF4) are present in patients with atherosclerosis. To date, no direct in-vivo evidence exists for the involvement of PF4 atherogenesis. In current study, we tested hypothesis that is atherogenic, and genetic elimination would protect mice from We have bred PF4(-/-) onto two athero-susceptible backgrounds, WT-C57Bl/6(WT) apoE(-/-) to examine importance order induce atherosclerosis, WT were fed an atherogenic diet 30 weeks, while a high-fat...
The centromere—defined by the presence of nucleosomes containing histone H3 variant, CENP-A—is chromosomal locus required for accurate segregation chromosomes during cell division. Although sequence determinants human CENP-A to maintain a centromere were reported, those that are early steps in establishing new unknown. In this paper, we used gain-of-function chimeras various regions unique investigate events establishment. We targeted chromosomally integrated Lac operator sequences fusing...
Abstract Maintaining centromere identity relies upon the persistence of epigenetic mark provided by histone H3 variant, protein A (CENP-A), but molecular mechanisms that underlie its remarkable stability remain unclear. Here, we define contributions each three candidate CENP-A nucleosome-binding domains (two on CENP-C and one CENP-N) to using gene replacement rapid degradation. Surprisingly, most conserved domain, motif, is dispensable. Instead, conferred unfolded central domain folded...
Summary Emerging evidence supports a role for platelets in the progression of atherosclerosis addition to an involvement thrombotic vascular occlusion. Platelet Factor 4 (PF4), chemokine released by activated platelets, stimulates several pro-atherogenic processes. Therefore, we examined localization PF4 and homologous protein, Neutrophil Activating Protein-2 (NAP-2) lesions representing evolution human atherosclerotic plaques. Carotid plaques from 132 patients with critical carotid stenosis...
Retinal vasoconstriction and reduced retinal blood flow precede the onset of diabetic retinopathy. The pathophysiological mechanisms that underlie increased arteriolar tone during diabetes remain unclear. Normally, local Ca(2+) release events (Ca(2+)-sparks), trigger activation large-conductance Ca(2+)-activated K(+)(BK)-channels which hyperpolarize relax vascular smooth muscle cells, thereby causing vasodilatation. In present study, we examined BK channel function in cells from...
Abstract Alternative splicing of neuronal genes is controlled partly by the coordinated action polypyrimidine tract binding proteins (PTBPs). While PTBP1 ubiquitously expressed, PTBP2 predominantly neuronal. Here, we define footprint in human transcriptome using brain tissue and induced pluripotent stem cell-derived neurons (iPSC-neurons). We map sites, characterize PTBP2-dependent alternative events, identify novel targets including SYNGAP1 , a synaptic gene whose loss-of-function leads to...
Three-dimensional (3D) tracking can provide valuable biological insights that are missing in conventional microscopy. Here we developed a single molecule 3D microscopy technique, named Parallax, with high localization precision and temporal resolution. We demonstrated its capabilities by studying the trafficking of glucose-transporter-4 containing vesicles living adipocytes as well walking path myosin VI molecules along actin filaments.
Little is known about the molecular characteristics of voltage-activated K(+) (K(v)) channels that underlie A-type current in vascular smooth muscle cells systemic circulation. We investigated identity retinal arteriolar myocytes using patch-clamp techniques, RT-PCR, immunohistochemistry, and neutralizing antibody studies. The was resistant to actions specific inhibitors for K(v)3 K(v)4 but blocked by K(v)1 antagonist correolide. No effects were observed with pharmacological agents against...
myo1c is a single-headed myosin that dynamically links membranes to the actin cytoskeleton. A putative pleckstrin homology domain has been identified in tail binds phosphoinositides and soluble inositol phosphates with high affinity. However, kinetics of association dissociation influence phospholipid composition on have not determined. Stopped-flow spectroscopy was used measure binding recombinant construct containing regulatory domains (myo1cIQ-tail) from 100-nm diameter large unilamellar...
By their control of membrane potential and intracellular free Ca(2+) ([Ca(2+)](i)), K(+) currents are pivotal in the regulation arterial smooth muscle tone. The goal present study was to identify characterize A-type current retinal microvascular (MVSM) examine its role modulating cellular contractility.Whole-cell perforated patch-clamp recordings were made from MVSM cells within intact isolated arteriolar segments. Before patch-clamping, arterioles anchored physiological recording bath...
In adipocytes, vesicles containing glucose transporter-4 (GLUT4) redistribute from intracellular stores to the cell periphery in response insulin stimulation. Vesicles then fuse with plasma membrane, facilitating transport into cell. To gain insight details of microtubule involvement, we examined spatial organization and dynamics microtubules relation GLUT4 vesicle trafficking living 3T3-L1 adipocytes using total internal reflection fluorescence (TIRF) microscopy. Insulin stimulated an...
Mammalian centromeres direct faithful genetic inheritance and are typically characterized by regions of highly repetitive rapidly evolving DNA. We focused on a mouse species,
To identify spontaneous Ca(2+) sparks and global oscillations in microvascular smooth muscle (MVSM) cells within intact retinal arterioles to characterize their spatiotemporal properties physiological functions.Retinal were mechanically dispersed from freshly isolated rat retinas loaded with Fluo-4, a Ca(2+)-sensitive dye. Changes [Ca(2+)](i) imaged MVSM situ by confocal scanning laser microscopy x-y mode or line-scan mode.The scans revealed discretely localized, events resembling more...
Aurora B, together with IN-box, the C-terminal part of INCENP, forms an enzymatic complex that ensures faithful cell division. The [Aurora B/IN-box] is activated by autophosphorylation in B activation loop and but it not clear how these phosphorylations activate enzyme. We used a combination experimental computational studies to investigate effects phosphorylation on molecular dynamics structure B/IN-box]. In addition, we generated partially phosphorylated intermediates analyze contribution...
The Small Business Innovation Research (SBIR) program was created to stimulate technological innovation and business development at early stage companies in the United States. In its 21-year history, has channeled over $35 billion of public funds private businesses form approximately 137,000 grants. However, question whether SBIR funding effectively spurs new promotes commercialization remains controversial. Here, we review efforts answer this perform an independent analysis evaluate success...
Mammalian centromeres direct faithful genetic inheritance and are typically characterized by regions of highly repetitive rapidly evolving DNA. We focused on a mouse species, Mus pahari, that we found has evolved to house centromere-specifying CENP-A nucleosomes at the nexus satellite repeat identified term π-satellite (π-sat), small number recruitment sites for CENP-B, short stretches perfect telomere repeats. One M. pahari chromosome, however, houses radically divergent centromere...