A5048599780- Angiogenesis and VEGF in Cancer
- Barrier Structure and Function Studies
- Hippo pathway signaling and YAP/TAZ
- Ultrasound and Hyperthermia Applications
- Zebrafish Biomedical Research Applications
- Axon Guidance and Neuronal Signaling
- Congenital heart defects research
- Electrospun Nanofibers in Biomedical Applications
- Cancer-related molecular mechanisms research
- Connexins and lens biology
- Photoacoustic and Ultrasonic Imaging
- Pregnancy and preeclampsia studies
- Neuroscience and Neuropharmacology Research
- TGF-β signaling in diseases
- Lymphatic System and Diseases
- Cell Adhesion Molecules Research
- Ultrasound and Cavitation Phenomena
- Cardiac and Coronary Surgery Techniques
- Retinal Imaging and Analysis
- Kruppel-like factors research
- RNA Research and Splicing
- Mathematical Biology Tumor Growth
- Cancer, Hypoxia, and Metabolism
- Acute Ischemic Stroke Management
- Retinal Diseases and Treatments
Biomedical Research Institute
2019-2023
Virginia Tech
2016-2023
Carilion Clinic
2018-2023
Carilion Roanoke Memorial Hospital
2016-2022
University of North Carolina at Chapel Hill
2008-2019
Pfizer (United States)
2011
UNC Lineberger Comprehensive Cancer Center
2011
Franklin & Marshall College
2011
Yale University
2011
University of Virginia Health System
2007-2008
Blood vessel formation requires the integrated regulation of endothelial cell proliferation and branching morphogenesis, but how this coordinated is achieved not well understood. Flt-1 (vascular growth factor [VEGF] receptor 1) a high affinity VEGF-A whose loss leads to overgrowth dysmorphogenesis. We examined ability isoform transgenes rescue vascular development embryonic stem cell–derived flt-1−/− mutant vessels. Endothelial was equivalently rescued by both soluble (sFlt-1)...
Perisynaptic Schwann cells (PSCs) are specialized, non-myelinating, synaptic glia of the neuromuscular junction (NMJ), that participate in synapse development, function, maintenance, and repair. The study PSCs has relied on an anatomy-based approach, as identities cell-specific PSC molecular markers have remained elusive. This limited approach precluded our ability to isolate genetically manipulate a cell specific manner. We identified neuron-glia antigen 2 (NG2) unique marker S100β+...
Abstract Therapeutic strategies in which recombinant growth factors are injected to stimulate arteriogenesis patients suffering from occlusive vascular disease stand benefit improved targeting, less invasiveness, better growth‐factor stability, and more sustained release. A microbubble contrast‐agent‐based system facilitates nanoparticle deposition tissues that targeted by 1‐MHz ultrasound. This can then be used deliver poly( D , L ‐lactic‐co‐glycolic acid) nanoparticles containing...
Blood vessel formation is essential for vertebrate development and primarily achieved by angiogenesis - endothelial cell sprouting from pre-existing vessels. Vessel networks expand when sprouts form new connections, a process whose regulation poorly understood. Here, we show that anastomosis spatially regulated Flt1 (VEGFR1), VEGFA receptor acts as decoy receptor. In vivo, expanding favor interactions with mutant mouse cells. Live imaging in human cells vitro revealed stable connections are...
In developing blood vessel networks, the overall level of branching often correlates with angiogenic sprout initiations, but in some pathological situations, increased initiations paradoxically lead to reduced and impaired vascular function. We examine hypothesis that defects discrete stages angiogenesis can uniquely contribute outcomes. Time-lapse movies mammalian development were used define quantify dynamics sprouting. characterized formation new functional conduits by classifying...
Objective— Vascular endothelial growth factor (VEGF) signaling induces Notch during angiogenesis. Flt-1/VEGF receptor-1 negatively modulates VEGF signaling. Therefore, we tested the hypothesis that disrupted Flt-1 regulation of causes pathway defects contribute to dysmorphogenesis mutant vessels. Approach and Results— Wild-type flt-1 −/− mouse embryonic stem cell–derived vessels were exposed pharmacological protein-based inhibitors with without added VEGF. Vessel morphology, cell...
Diabetic retinopathy is a potentially blinding eye disease that threatens the vision of one-ninth patients with diabetes. Progression has long been attributed to an initial dropout pericytes enwrap retinal microvasculature. Revealed through vascular digests, subsequent increase in basement membrane bridges was also observed. Using cell-specific markers, we demonstrate rather than endothelial cells colocalize these bridges. We show density transiently increases elevation Ang-2, PDGF-BB, and...
Vascular pericytes stabilize blood vessels and contribute to their maturation, while playing other key roles in microvascular function. Nevertheless, relatively little is known about involvement of precursors the earliest stages vascular development, specifically during vasculogenesis.
We developed an agent-based model of endothelial sprout initiations based on time-lapse confocal imaging <italic>in vitro</italic> that outperforms Monte Carlo simulations, suggesting location and frequency are not purely stochastic behaviors.
Abstract Pericytes are critical for microvascular stability and maintenance, among other important physiological functions, yet their involvement in vessel formation processes remains poorly understood. To gain insight into pericyte behaviors during vascular remodeling, we developed two complementary tissue explant models utilizing ‘double reporter’ animals with fluorescently-labeled pericytes endothelial cells (via Ng2:DsRed Flk-1:eGFP genes, respectively). Time-lapse confocal imaging of...
Experimental data indicates that soluble vascular endothelial growth factor (VEGF) receptor 1 (sFlt-1) modulates the guidance cues provided to sprouting blood vessels by VEGF-A. To better delineate role of sFlt-1 in VEGF signaling, we have developed an experimentally based computational model. This model describes dynamic spatial transport VEGF, and its binding receptors Flt-1 Flk-1, a mouse embryonic stem cell vessel morphogenesis. The represents local environment single vessel. Our...
Define a role for perivascular cells during developmental retinal angiogenesis in the context of EC Notch1-DLL4 signaling at multicellular network level.The vasculature is highly sensitive to growth factor-mediated intercellular signaling. Although has been explored detail, it remains unclear how PC function modulate these signals that lead diverse set vascular patterns health and disease. We have developed an ABM incorporates both ECs PCs investigate formation as pericyte coverage. use our...
Objective— We have previously shown that, under certain conditions, ultrasonic microbubble destruction creates arteriogenesis and angiogenesis in skeletal muscle. Here, we tested whether this neovascularization response enhances hyperemia a rat model of arterial insufficiency is dependent on the recruitment bone marrow–derived cells (BMDCs) to treated tissues via β2 integrin (CD18)-dependent mechanism. Methods Results— Sprague-Dawley rats, C57BL/6 wild-type mice, chimeric mice engrafted with...