A5065994871- Sphingolipid Metabolism and Signaling
- Endoplasmic Reticulum Stress and Disease
- Eicosanoids and Hypertension Pharmacology
- Nitric Oxide and Endothelin Effects
- Lipid Membrane Structure and Behavior
- Adipose Tissue and Metabolism
- Cancer, Hypoxia, and Metabolism
- Angiogenesis and VEGF in Cancer
- Erythrocyte Function and Pathophysiology
- Cellular transport and secretion
- Renin-Angiotensin System Studies
- Cardiac Imaging and Diagnostics
- PI3K/AKT/mTOR signaling in cancer
- ATP Synthase and ATPases Research
- Caveolin-1 and cellular processes
- Cardiovascular Disease and Adiposity
- Lipid metabolism and disorders
- Cardiac Fibrosis and Remodeling
- Lanthanide and Transition Metal Complexes
- Chemotherapy-induced cardiotoxicity and mitigation
- Sulfur Compounds in Biology
- Receptor Mechanisms and Signaling
- Cell Adhesion Molecules Research
- Cardiovascular Function and Risk Factors
- Mast cells and histamine
MIND Research Institute
2019-2025
Cornell University
2016-2025
Weill Cornell Medicine
2016-2025
Cardiovascular Institute Hospital
2019-2024
University of Naples Federico II
2005-2017
NYU Langone Health
2016
Yale University
2004-2015
Center for Vascular Biology Research
2010
New York University
2009
University of Florence
2005
Akt1 is implicated in cell metabolism, survival migration, and gene expression; however, little known about the role of specific Akt isoforms during inflammation vivo. Thus, we directly explored roles Akt2 acute models by using mice deficient either or Akt2. −/− showed a markedly reduced edema versus WT controls, was associated with dramatic decrease neutrophil monocyte infiltration. The loss did not affect leukocyte functions vitro, bone marrow transplant experiments suggest that host...
Cerebral cavernous malformation is a common human vascular disease that arises due to loss-of-function mutations in genes encoding three intracellular adaptor proteins, cerebral malformations 1 protein (CCM1), CCM2, and CCM3. CCM1, CCM3 interact biochemically pathway required endothelial cells during cardiovascular development mice zebrafish. The downstream effectors by which this signaling regulates function have not yet been identified. Here we shown zebrafish expression of mutant ccm3...
Objective— Deletion of Akt1 leads to severe atherosclerosis and occlusive coronary artery disease. Vascular smooth muscle cells (VSMCs) are an important component atherosclerotic plaques, responsible for promoting plaque stability in advanced lesions. Fibrous caps unstable plaques contain less collagen ECM components fewer VSMCs than from stable Here, we investigated the role VSMC proliferation, migration, oxidative stress–induced apoptosis. In addition, also characterized morphology cardiac...
Transient disruption of endothelial adherens junctions and cytoskeletal remodeling are responsible for increases in vascular permeability induced by inflammatory stimuli growth factor (VEGF). Nitric oxide (NO) produced NO synthase (eNOS) is critical VEGF changes vivo, however, the molecular mechanisms which endogenous modulates not clear. Here we show that lack eNOS reduces permeability, an effect mediated enhanced Rac-GTPase activation stabilization cortical actin. The loss NO, increased...
Phenotypic modulation of smooth muscle cells (SMCs) plays a key role in vascular disease, including atherosclerosis. Several transcription factors have been suggested to regulate phenotypic SMCs but the decisive mechanisms remain unknown. Recent reports suggest that specific microRNAs (miRNAs) are involved SMC differentiation and disease global miRNAs postnatal has not elucidated. Thus, objective this study was identify Dicer-dependent for blood pressure regulation contractile function vivo....
Nitric oxide is one of the major endothelial-derived vasoactive factors that regulate blood pressure (BP), and bioactive lipid mediator S1P (sphingosine-1-phosphate) a potent activator endothelial nitric synthase through G protein-coupled receptors. Endothelial-derived autocrine/paracrine activation S1PR (S1P receptors) play an important role in preserving vascular functions BP homeostasis. Furthermore, FTY720 (fingolimod), binding to 4 out 5 S1PRs recently approved by Food Drug...
Abstract Although kidney parenchymal tissue can be generated in vitro, reconstructing the complex vasculature of remains a daunting task. The molecular pathways that specify and sustain functional, phenotypic structural heterogeneity are unknown. Here, we employ high-throughput bulk single-cell RNA sequencing non-lymphatic endothelial cells (ECs) to identify dictate vascular zonation from embryos adulthood. We show manifests vascular-specific signatures expressing defined transcription...
The lipid distribution of plasma membranes eukaryotic cells is asymmetric and phospholipid scramblases disrupt this asymmetry by mediating the rapid, nonselective transport lipids down their concentration gradients. As a result, phosphatidylserine exposed to outer leaflet membrane, an important step in extracellular signaling networks controlling processes such as apoptosis, blood coagulation, membrane fusion repair. Several TMEM16 family members have been identified Ca2+-activated...
Apolipoprotein M (ApoM) transports sphingosine-1-phosphate (S1P) in plasma, and ApoM-deficient mice (Apom–/–) have ~50% reduced plasma S1P levels. There are 5 known receptors, induces adherens junction formation between endothelial cells through the S1P1 receptor, which turn suppresses vascular leak. Increased permeability is a hallmark of inflammation. The purpose this study was to explore relationships leakage ApoM deficiency function normal physiology Vascular lungs assessed by...
Cardiovascular diseases could be treated by chaperones that deliver the lipid mediator S1P promotes endothelial function.
Growing evidence correlated changes in bioactive sphingolipids, particularly S1P (sphingosine-1-phosphate) and ceramides, with coronary artery diseases. Furthermore, specific plasma ceramide species can predict major cardiovascular events. Dysfunction of the endothelium lining lesion-prone areas plays a pivotal role atherosclerosis. Yet, how sphingolipid metabolism signaling change contribute to endothelial dysfunction atherosclerosis remain poorly understood.
Although intimately positioned between metabolic substrates in the bloodstream and tissue parenchymal cells that require these substrates, a major role of vascular endothelium regulation metabolism has not been widely appreciated. We hypothesized via control transendothelial glucose transport contributing paracrine mechanisms plays regulating organ metabolism. further hypoxia-inducible factor -1α (HIF-1α) an important coordinating endothelial functions. To test hypotheses, we generated mice...
Akt mediates postnatal angiogenesis through eNOS signaling.
Ceramides are sphingolipids that modulate a variety of cellular processes via 2 major mechanisms: functioning as second messengers and regulating membrane biophysical properties, particularly lipid rafts, important signaling platforms. Altered sphingolipid levels have been implicated in many cardiovascular diseases, including hypertension, atherosclerosis, diabetes mellitus-related conditions; however, molecular mechanisms by which ceramides impact endothelial functions remain poorly...
Sphingosine-1-phosphate (S1P) has been shown to regulate numerous and diverse cell functions, including smooth muscle contraction. Here we assessed the role of S1P/Sphingosine kinase (SPK) pathway in regulation bronchial tone. Our objective was determine, using an integrated pharmacologic molecular approach, (1) S1P as endogenous modulator tone, (2) linkage between hyperresponsiveness. We evaluated effects on isolated bronchi whole lungs, harvested from Balb/c mice sensitized ovalbumin (OVA)...
Blood vessel formation during ischemia and wound healing requires coordination of the inflammatory response with genes that regulate blood assembly. Here we show reticulon family member 4B, aka Nogo-B, is upregulated in to necessary for flow recovery secondary healing. Mice lacking Nogo-B exhibit reduced arteriogenesis angiogenesis are linked a decrease macrophage infiltration gene expression vivo. Bone marrow-derived macrophages isolated from Nogo knock-out mice have spreading chemotaxis...
We recently discovered that endothelial Nogo-B, a membrane protein of the ER, regulates vascular function by inhibiting rate-limiting enzyme, serine palmitoyltransferase (SPT), in de novo sphingolipid biosynthesis. Here, we show endothelium-derived sphingolipids, particularly sphingosine-1-phosphate (S1P), protect heart from inflammation, fibrosis, and dysfunction following pressure overload Nogo-B this paracrine process. SPT activity is upregulated banded hearts vivo as well TNF-α–activated...
Bioactive sphingolipids are emerging as key regulators of vascular function and homeostasis. While most the clinical studies have been devoted to profile circulating in maternal plasma, little is known about role sphingolipid at feto-placental vasculature, which direct contact with offspring circulation. Our study aims compare normal preeclamptic (PE) placental chorionic arteries isolated endothelial cells, goal unveiling potential underlying pathomechanisms vasculature. Dihydrosphingosine...
Here, by using in vitro and ex vivo approaches, we elucidate the impairment of hydrogen sulfide (H2S) pathway vascular complications associated with metabolic syndrome (MetS). In model simulating hyperlipidemic/hyperglycemic conditions, observe significant hallmarks endothelial dysfunction, including eNOS/NO signaling impairment, ROS overproduction, a reduction CSE-derived H2S. Transitioning to an db/db mice, genetic MetS model, identify downregulation CBS CSE expression aorta, coupled...