A5042212411- Respiratory Support and Mechanisms
- Inhalation and Respiratory Drug Delivery
- Neonatal Respiratory Health Research
- Asthma and respiratory diseases
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Neuroscience of respiration and sleep
- Pulmonary Hypertension Research and Treatments
- Respiratory and Cough-Related Research
- Congenital Diaphragmatic Hernia Studies
- Airway Management and Intubation Techniques
- Genomics, phytochemicals, and oxidative stress
- Hemodynamic Monitoring and Therapy
- Air Quality and Health Impacts
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Tracheal and airway disorders
- Respiratory viral infections research
- IL-33, ST2, and ILC Pathways
- Angiogenesis and VEGF in Cancer
- Heart Rate Variability and Autonomic Control
- Obstructive Sleep Apnea Research
- Epigenetics and DNA Methylation
- Optical Coherence Tomography Applications
- Cancer, Hypoxia, and Metabolism
- Atomic and Subatomic Physics Research
- Cardiac Arrest and Resuscitation
Johns Hopkins University
2015-2024
Public Health Department
2024
Johns Hopkins Medicine
1995-2023
Johns Hopkins Bayview Medical Center
1988-2023
Bloomberg (United States)
2020-2023
CVRx (United States)
2012
University of Bern
2010
University of Pennsylvania
2006
Siriraj Hospital
2003
Mahidol University
2003
Oxidative stress has been postulated to play an important role in the pathogenesis of asthma; although a defect antioxidant responses speculated exacerbate asthma severity, this difficult demonstrate with certainty. Nuclear erythroid 2 p45-related factor (Nrf2) is redox-sensitive basic leucine zipper transcription that involved transcriptional regulation many genes. We show disruption Nrf2 gene leads severe allergen-driven airway inflammation and hyperresponsiveness mice. Enhanced asthmatic...
Significance Idiopathic pulmonary fibrosis and emphysema are leading causes of mortality, but there no effective therapies. Mutations in telomerase the most common identifiable risk factor for idiopathic fibrosis. They also predispose to severe smokers, occurring at a frequency similar α-1 antitrypsin deficiency. The work shown here points alveolar stem cell senescence as driver these pathologies. Epithelial failure was associated with secondary inflammatory recruitment exquisite...
Germline mutations in the enzyme telomerase cause telomere shortening, and have their most common clinical manifestation age-related lung disease that manifests as idiopathic pulmonary fibrosis. Short telomeres are also a unique heritable trait is acquired with age.We sought to understand mechanisms by which deficiency contributes disease.We studied null mice short telomeres.Although they no baseline histologic defects, when exposed chronic cigarette smoke, contrast controls, develop...
The mouse is the species of choice for creating genetically engineered models human disease. To study detailed systolic and diastolic left ventricular (LV) chamber mechanics in mice vivo, we developed a miniaturized conductance-manometer system. α-Chloralose-urethan-anesthetized animals were instrumented with two-electrode pressure-volume catheter advanced via LV apex to aortic root. Custom electronics provided time-varying conductances related cavity volume. Baseline hemodynamics similar...
There is increasing interest in the structural components of airway wall because remodeling that observed conditions such as asthma and chronic obstructive pulmonary disease their contribution to changes mechanics. This has stimulated several groups make morphometric measurements on cross sections, results have been reported using a variety nomenclature. We propose adoption standard system nomenclature based accepted terms for subdivisions agreed by working this field.
An increased airway response to various bronchoconstricting agents is one of the hallmarks asthma. interdependence heredity and environment appears determine this nonspecific hyperreactivity airways. The present study describes patterns inheritance a direct mediator smooth muscle contraction (acetylcholine) in A/J C3H/HeJ inbred mice their offspring. mean acetylcholine was greater than sixfold higher as compared with mice. Two phenotypes were easily distinguished on basis responses progeny...
Chronic obstructive pulmonary disease (COPD) is a prevalent smoking-related for which no disease-altering therapies currently exist. As dysregulated TGF-β signaling associates with lung pathology in patients COPD and animal models of injury induced by chronic exposure to cigarette smoke (CS), we postulated that inhibiting would protect against CS-induced injury. We first confirmed was the lungs mice chronically exposed CS as well patient samples. Importantly, key pathological features...
Purpose:. Stabilization of the transcription factor NRF2 through genomic alterations in KEAP1 and NFE2L2 occurs a quarter patients with lung adenocarcinoma third squamous cell carcinoma. In adenocarcinoma, loss often co-occurs STK11 KRAS-activating alterations. Despite its prevalence, impact activation on tumor progression patient outcomes is not fully defined.Experimental Design:. We model activation, loss, KRAS vivo using novel genetically engineered mouse models. Furthermore, we derive...
Myocarditis and dilated cardiomyopathy (DCM) are often caused by viral infections occur more frequently in men than women, but the reasons for sex difference remain unclear. The aim of this study was to assess whether gene changes heart during coxsackievirus B3 (CVB3) myocarditis male female BALB/c mice predicted worse DCM males. Although (P = 4.2 × 10(-5)) cardiac dilation 0.008) were males, there no replication heart. Fibrotic remodeling genes, such as tissue inhibitor metalloproteinase...
Abstract Alternatively activated macrophages (M2) have an important function in innate immune responses to parasitic helminths, and emerging evidence also indicates these cells are regulators of systemic metabolism. Here we show a critical role for mTORC2 signalling the generation M2 macrophages. Abrogation by selective conditional deletion adaptor molecule Rictor inhibits while leaving classically (M1) intact. Selective prevents differentiation clearance helminth infection mice, abrogates...
Over 100 million women use progesterone therapies worldwide. Despite having immunomodulatory and repair properties, their effects on the outcome of viral diseases outside reproductive tract have not been evaluated. Administration exogenous (at concentrations that mimic luteal phase) to progesterone-depleted adult female mice conferred protection from both lethal sublethal influenza A virus (IAV) infection. Progesterone treatment altered inflammatory environment lungs, but had no load....
Despite intense investigation, acute respiratory distress syndrome (ARDS) remains an enormous clinical problem for which no specific therapies currently exist. In this study, we used intratracheal lipopolysaccharide or Pseudomonas bacteria administration to model experimental lung injury (ALI) and further understand mediators of the resolution phase ARDS. Recent work demonstrates macrophages transition from a predominant proinflammatory M1 phenotype during inflammation anti-inflammatory M2...
A profile of respiratory complications has been associated with the onset and development obesity in humans. Similar phenotypes have routinely demonstrated genetic animal models such as ob mouse (C57BL/6J- Lep ). The objective present study was to test hypothesis that a constellation are attenuated leptin (i.e., protein product gene) replacement. Daily administration during 6-wk period conducted control body weight mutant mice similar genotypic groups. During treatment period, repeated...
A method was devised to computationally segment and measure three-dimensional pulmonary trees in situ. Bronchi vessels were extracted from volumetric computed tomography data based on radiopacity differences between airway wall lumen blood parenchyma, respectively. The tree reduced a central axis facilitate measurement of branch length angle. Cross-sectional area measured reconstructed slice perpendicular this axis. validated by scanning two Plexiglas phantoms an intact lung. Reconstructed...
The ability to successfully intubate the trachea of mice and control their ventilation is important for longitudinal studies requiring recovery from anesthesia repeated pulmonary function measurements or other evaluations, such as use radiological imaging (e.g., computed tomography magnetic resonance imaging). We describe a method rapid intubation mice, with subsequent at baseline after an agonist challenge. simply constructed metal blade used laryngoscope facilitate oropharyngeal exposure,...
We have previously reported that airway hyperresponsiveness to acetylcholine (ACh) is inherited as an autosomal recessive trait in A/J and C3H/HeJ mice the progeny of crosses between them (FASEB J. 2: 2605–2608, 1988). In present report, we extended these studies by evaluating biological variability response 5-hydroxytryptamine (5-HT) ACh among multiple genetically standardized inbred strains mice. The pattern responsiveness differed significantly from 5-HT nine showed nonspecific both ACh....
Studies and applications of high-frequency ventilation (HFV) are often performed under conditions controlled mean airway pressure (Paw). In the present study we tested assumption that controlling Paw adequately controls lung volume during HFV by investigating relationship between a reliably measured alveolar (Palv) lungs healthy dogs. We minimized errors measurement due to Bernoulli effect various technical factors appropriate choice transducers, amplifiers, site. Palv was estimated clamping...