A5026125920- Caveolin-1 and cellular processes
- Erythrocyte Function and Pathophysiology
- Immunotherapy and Immune Responses
- Angiogenesis and VEGF in Cancer
- Ion Transport and Channel Regulation
- Phagocytosis and Immune Regulation
- Cancer Mechanisms and Therapy
- Fibroblast Growth Factor Research
- Cell Adhesion Molecules Research
- Cancer-related molecular mechanisms research
- Lipid metabolism and disorders
- Cancer Immunotherapy and Biomarkers
- Kruppel-like factors research
- Immune cells in cancer
- Cancer, Hypoxia, and Metabolism
- Cellular transport and secretion
- Renal Diseases and Glomerulopathies
- Chronic Obstructive Pulmonary Disease (COPD) Research
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Chronic Kidney Disease and Diabetes
- Glycosylation and Glycoproteins Research
- ATP Synthase and ATPases Research
- Signaling Pathways in Disease
- Proteoglycans and glycosaminoglycans research
Dartmouth College
2012-2023
Dartmouth–Hitchcock Medical Center
2017-2020
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2017
IFOM
2017
Uppsala University
2017
Yale University
2004-2016
VA Connecticut Healthcare System
2016
Cotton (United States)
2012
Angiogenesis Foundation
2007
Dartmouth Psychiatric Research Center
2006
Caveolins are important components of caveolae, which have been implicated in vesicular trafficking and signal transduction. To investigate the vivo significance mammals, we generated mice deficient caveolin-1 (cav-1) gene shown that, absence Cav-1, no caveolae structures were observed several nonmuscle cell types. Although cav-1(-/-) viable, histological examination echocardiography identified a spectrum characteristics dilated cardiomyopathy left ventricular chamber cav-1-deficient hearts,...
Mitochondrial division requires of both the inner and outer mitochondrial membranes (IMM OMM, respectively). Interaction with endoplasmic reticulum (ER) promotes OMM by recruitment dynamin Drp1, but effects on IMM are not well characterized. We previously showed that actin polymerization through ER-bound inverted formin 2 (INF2) stimulates Drp1 in mammalian cells. Here, we show INF2-mediated a second response independent Drp1: rise matrix calcium uniporter. ER stores supply increased...
The integrity of the endothelial monolayer is essential to blood vessel homeostasis and active regulation permeability. FGF system plays important roles in a wide variety physiologic pathologic conditions; however, its role adult vasculature has not been defined. To assess monolayer, we disrupted signaling bovine aortic cells human saphenous vein vitro mouse rat vivo using soluble traps or dominant inhibitor all receptors. inhibition these approaches resulted dissociation...
PV-1 is a novel endothelial protein shown by immunocytochemical tests to be specifically associated with the stomatal diaphragms of caveolae in lung endothelium. Although highest expression levels both mRNA and are lung, also has been found expressed other organs. Using specific antibody extracellular domain PV-1, we have extended survey on presence this at light electron microscope level several rat Here show that immunofluorescence recognizes high specificity endothelium fenestrated...
Plasmalemmal vesicles (PVs) or caveolae are plasma membrane invaginations and associated of regular size shape found in most mammalian cell types. They particularly numerous the continuous endothelium certain microvascular beds (e.g., heart, lung, muscles) which they have been identified as transcytotic vesicular carriers. Their chemistry function extensively studied last years by various means, including several attempts to isolate them fractionation from different The methods so far used...
Various cellular signals initiate calcium entry into cells, and there is evidence that lipid rafts caveolae may concentrate proteins regulate transmembrane fluxes. Here, using mice deficient in caveolin-1 (Cav-1) Cav-1 knock-out reconstituted with endothelium-specific Cav-1, we show essential for endothelial cells governs the localization protein-protein interactions between transient receptor channels C4 C1. Thus, required vascular perhaps other specialized cell types containing caveolae.
The specific role of VEGFA-induced permeability and vascular leakage in physiology pathology has remained unclear. Here we show that depends on signalling initiated via the VEGFR2 phosphosite Y949, regulating dynamic c-Src VE-cadherin phosphorylation. Abolished Y949 mouse mutant Vegfr2(Y949F/Y949F) leads to VEGFA-resistant endothelial adherens junctions a block molecular extravasation. Vessels mice remain sensitive inflammatory cytokines, morphology, blood pressure flow parameters are...
Abstract Molecular targeting of nanoparticle drug carriers promises maximized therapeutic impact to sites disease or injury with minimized systemic effects. Precise demands addressing subcellular features. Caveolae, invaginations in cell membranes implicated transcytosis and inflammatory signaling, are appealing targets. Caveolar geometry has been reported impose a ≈50 nm size cutoff on nanocarrier access plasmalemma vesicle associated protein (PLVAP), marker found caveolae the lungs. The...
The functions of caveolae and/or caveolins in intact animals are beginning to be explored. Here, by using endothelial cell-specific transgenesis the caveolin-1 (Cav-1) gene mice, we show critical role Cav-1 several postnatal vascular paradigms. First, increasing levels do not increase number endothelium vivo . Second, despite a lack quantitative changes organelle number, endothelial-specific expression impairs nitric oxide synthase activation, barrier function, and angiogenic responses...
Full activity of fibroblast growth factors (FGFs) requires their internalization in addition to the interaction with cell surface receptors. Recent studies have suggested that transmembrane proteoglycan syndecan-4 functions as a FGF2 receptor. In this study we investigated molecular basis syndecan endocytosis and its role endothelial cells. We found uptake, induced either by treatment or antibody clustering, integrity plasma membrane lipid rafts for initiation, occurs non-clathrin-,...
PV1 is an endothelial-specific integral membrane glycoprotein associated with the stomatal diaphragms of caveolae, transendothelial channels, and vesiculo-vacuolar organelles endothelial fenestrae. Multiple homodimers are found within each fenestral diaphragm. We investigated function these their regulation that treatment cells in culture phorbol myristate acetate (PMA) led to upregulation PV1. This correlated de novo formation caveolae channels as well fenestrae upon PMA treatment. The...
Dendritic cells (DC) and cytokines that expand myeloid progenitors are widely used to treat cancer. Here, we show CD11c(+)DEC205(+) DCs coexpressing alpha-smooth muscle actin VE-cadherin home perivascular areas in the ovarian cancer microenvironment required for maintenance of tumor vasculature. Consequently, depletion mice bearing established by targeting different specific markers significantly delays growth enhances effect standard chemotherapies. Tumor restriction was associated with...
Unlike most fenestrated capillary endothelial cells, adult glomerular cells (GEnC) are generally thought to lack diaphragms at their fenestrae, but this remains controversial. In study, morphologic and immunocytochemical analyses demonstrated that, except for a small fraction, GEnC of rats lacked diaphragmed which contain the transmembrane glycoprotein PV-1. contrast, in embryonic exhibited fenestrae expressed PV-1 protein. The luminal surface fenestral diaphragm possesses high density...