A5068367251- Heme Oxygenase-1 and Carbon Monoxide
- Autophagy in Disease and Therapy
- Neonatal Health and Biochemistry
- Hemoglobin structure and function
- Inflammasome and immune disorders
- Thermal Regulation in Medicine
- Cannabis and Cannabinoid Research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Alcohol Consumption and Health Effects
- Neuroscience of respiration and sleep
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Cell death mechanisms and regulation
- Respiratory Support and Mechanisms
- Endoplasmic Reticulum Stress and Disease
- Caveolin-1 and cellular processes
- High Altitude and Hypoxia
- Extracellular vesicles in disease
- Eicosanoids and Hypertension Pharmacology
- Erythrocyte Function and Pathophysiology
- Photodynamic Therapy Research Studies
- Neonatal Respiratory Health Research
- Phagocytosis and Immune Regulation
- Mitochondrial Function and Pathology
- Sulfur Compounds in Biology
- Adipose Tissue and Metabolism
Cornell University
2014-2023
New York Hospital Queens
2014-2023
NewYork–Presbyterian Hospital
2014-2023
Presbyterian Hospital
2014-2023
Weill Cornell Medicine
2018-2022
Federal Department of Defence, Civil Protection and Sports
2019
Pulmonary and Critical Care Associates
2011-2018
Brigham and Women's Hospital
2008-2016
Harvard University
2008-2016
Harvard University Press
2008-2013
Reactive oxygen or nitrogen species (ROS/RNS) generated endogenously in response to environmental stress have long been implicated tissue injury the context of a variety disease states. ROS/RNS can cause cell death by nonphysiological (necrotic) regulated pathways (apoptotic). The mechanisms which regulate apoptosis typically include receptor activation, caspase Bcl-2 family proteins, and mitochondrial dysfunction. Various protein kinase activities, including mitogen-activated kinases,...
The pathogenesis of chronic obstructive pulmonary disease (COPD) remains unclear, but involves loss alveolar surface area (emphysema) and airway inflammation (bronchitis) as the consequence cigarette smoke (CS) exposure. Previously, we demonstrated that autophagy proteins promote lung epithelial cell death, dysfunction, emphysema in response to CS; however, underlying mechanisms have yet be elucidated. Here, using cultured cells murine models, CS causes mitochondrial dysfunction is...
Despite advances in clinical management, there are currently no reliable diagnostic and therapeutic targets for acute respiratory distress syndrome (ARDS). The inflammasome/caspase-1 pathway regulates the maturation secretion of proinflammatory cytokines (e.g., IL-18). IL-18 is associated with injury animal models systemic inflammation.We sought to determine contribution inflammasome experimental lung human ARDS.We performed comprehensive gene expression profiling on peripheral blood from...
Background Chronic obstructive pulmonary disease (COPD) is a progressive lung characterized by abnormal cellular responses to cigarette smoke, resulting in tissue destruction and airflow limitation. Autophagy degradative process involving lysosomal turnover of components, though its role human diseases remains unclear. Methodology Principal Findings Increased autophagy was observed from COPD patients, as indicated electron microscopic analysis, well increased activation autophagic proteins...
Chronic obstructive pulmonary disease (COPD) is a debilitating caused by chronic exposure to cigarette smoke (CS), which involves airway obstruction and alveolar loss (i.e., emphysema). The mechanisms of COPD pathogenesis remain unclear. Our previous studies demonstrated elevated autophagy in human lung, as cellular tissue response CS an experimental model emphysema vivo. We identified the autophagic protein microtubule-associated 1 light chain-3B (LC3B) positive regulator CS-induced lung...
The mammalian target of rapamycin complex 1 (mTORC1) regulates activation immune cells and cellular energy metabolism. Although glycolysis has been linked to functions, the mechanisms by which NLRP3 inflammasome remain unclear. Here, we demonstrate that mTORC1-induced provides an essential mechanism for activation. Moreover, hexokinase (HK1)-dependent glycolysis, under regulation mTORC1, represents a critical metabolic pathway Downregulation inhibition Raptor/mTORC1 or HK1 suppressed both...
Carbon monoxide (CO), a byproduct of heme catabolism by oxygenase (HO), confers potent antiinflammatory effects. Here we demonstrate that CO derived from HO-1 inhibited Toll-like receptor (TLR) 2, 4, 5, and 9 signaling, but not TLR3-dependent in macrophages. Ligand-mediated trafficking to lipid rafts represents an early event signal initiation immune cells. Trafficking TLR4 response LPS was reactive oxygen species (ROS) dependent because it diphenylene iodonium, inhibitor NADPH oxidase,...
Chronic obstructive pulmonary disease (COPD) involves aberrant airway inflammatory responses to cigarette smoke (CS) that are associated with epithelial cell dysfunction, cilia shortening, and mucociliary clearance disruption. Exposure CS reduced length induced autophagy in vivo differentiated mouse tracheal cells (MTECs). Autophagy-impaired (Becn1+/- or Map1lc3B-/-) mice MTECs resisted CS-induced shortening. Furthermore, increased the autophagic turnover of ciliary proteins, indicating may...
Proper regulation of mitophagy for mitochondrial homeostasis is important in various inflammatory diseases. However, the precise mechanisms by which activated to regulate responses remain largely unknown. The NLRP3 (NLR family, pyrin domain containing 3) inflammasome serves as a platform that triggers activation CASP1 (caspase 1) and secretion proinflammatory cytokines. Here, we demonstrate SESN2 (sestrin 2), known stress-inducible protein, suppresses prolonged clearance damaged mitochondria...
Cellular lipid metabolism has been linked to immune responses; however, the precise mechanisms by which de novo fatty acid synthesis can regulate inflammatory responses remain unclear. The NLRP3 inflammasome serves as a platform for caspase-1-dependent maturation and secretion of proinflammatory cytokines. Here, we demonstrated that mitochondrial uncoupling protein-2 (UCP2) regulates NLRP3-mediated caspase-1 activation through stimulation in macrophages. UCP2-deficient mice displayed...