A5026411789- Chronic Obstructive Pulmonary Disease (COPD) Research
- Sphingolipid Metabolism and Signaling
- Pulmonary Hypertension Research and Treatments
- Neonatal Respiratory Health Research
- Phagocytosis and Immune Regulation
- Protease and Inhibitor Mechanisms
- Respiratory Support and Mechanisms
- Erythrocyte Function and Pathophysiology
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Mesenchymal stem cell research
- Heme Oxygenase-1 and Carbon Monoxide
- Lipid Membrane Structure and Behavior
- Asthma and respiratory diseases
- Inhalation and Respiratory Drug Delivery
- Autophagy in Disease and Therapy
- Cardiovascular Function and Risk Factors
- Metabolomics and Mass Spectrometry Studies
- Fibroblast Growth Factor Research
- Air Quality and Health Impacts
- Cancer, Hypoxia, and Metabolism
- Cardiovascular and exercise physiology
- Peptidase Inhibition and Analysis
- Eicosanoids and Hypertension Pharmacology
- Long-Term Effects of COVID-19
- Immune cells in cancer
University of Colorado Denver
2016-2025
National Jewish Health
2016-2025
University of Colorado Anschutz Medical Campus
2017-2025
Indiana University – Purdue University Indianapolis
2013-2023
Indiana University School of Medicine
2010-2021
University of Colorado System
2018-2021
Johns Hopkins University
2000-2020
Denver Health Medical Center
2020
University of Colorado Health
2020
Richard L. Roudebush VA Medical Center
2010-2018
Although inflammation and protease/antiprotease imbalance have been postulated to be critical in cigarette smoke–induced (CS-induced) emphysema, oxidative stress has suspected play an important role chronic obstructive pulmonary diseases. Susceptibility of the lung injury, such as that originating from inhalation CS, depends largely on its upregulation antioxidant systems. Nuclear factor, erythroid-derived 2, like 2 (Nrf2) is a redox-sensitive basic leucine zipper protein transcription...
Although inflammation and protease/antiprotease imbalance have been postulated to be critical in cigarette smoke–induced (CS-induced) emphysema, oxidative stress has suspected play an important role chronic obstructive pulmonary diseases. Susceptibility of the lung injury, such as that originating from inhalation CS, depends largely on its upregulation antioxidant systems. Nuclear factor, erythroid-derived 2, like 2 (Nrf2) is a redox-sensitive basic leucine zipper protein transcription...
The increased use of inhaled nicotine via e-cigarettes has unknown risks to lung health. Having previously shown that cigarette smoke (CS) extract disrupts the microvasculature barrier function by endothelial cell activation and cytoskeletal rearrangement, we investigated contribution in CS or (e-Cig) injury. Primary microvascular cells were exposed nicotine, e-Cig solution, condensed vapor (1-20 mM nicotine) nicotine-free solutions. Compared with nicotine-containing extract, free-CS...
Exercise intolerance is a major manifestation of post-acute sequelae severe acute respiratory syndrome coronavirus infection (PASC, or "long-COVID"). in PASC associated with higher arterial blood lactate accumulation and lower fatty acid oxidation rates during graded exercise tests to volitional exertion, suggesting altered metabolism mitochondrial dysfunction. It remains unclear whether the profound disturbances that have been identified plasma from patients suffering disease 2019...
Tumor necrosis factor (TNF)-alpha, a major proinflammatory cytokine, triggers endothelial cell activation and barrier dysfunction which are implicated in the pathogenesis of pulmonary edema associated with acute lung injury syndromes. The mechanisms TNF-alpha-induced vascular permeability not completely understood. Our initial experiments demonstrated that decreases transendothelial electrical resistance across human artery cells independent myosin light chain phosphorylation catalyzed by...
Heme oxygenase (HO)-1 catalyzes the oxidative cleavage of heme to yield equimolar amounts biliverdin, iron, and carbon monoxide. HO-1 is a stress response protein, induction which associated with protection against stress. The mechanism(s) not completely elucidated, although it suggested that one or more catalytic by-products provide antioxidant functions either directly indirectly. involvement reactive oxygen species in apoptosis raised question possible role for programmed cell death....
Tumor necrosis factor (TNF)-α is released in acute inflammatory lung syndromes linked to the extensive vascular dysfunction associated with increased permeability and endothelial cell apoptosis. TNF-α induced significant decreases transcellular electrical resistance across pulmonary monolayers, reflecting barrier (beginning at 4 h persisting for 48 h). also triggered apoptosis beginning h, which was attenuated by caspase inhibitor Z-Val-Ala-Asp-fluoromethylketone. Exploring involvement of...
Rationale: There is growing evidence that alveolar cell apoptosis plays an important role in emphysema pathogenesis, a chronic inflammatory lung disease characterized by destruction. The association of α1-antitrypsin deficiency with the development has supported concept protease/antiprotease imbalance mediates cigarette smoke–induced emphysema.Objectives: We propose that, addition to its antielastolytic effects, may have broader biological effects lung, preventing through inhibition cells...
Adipose-derived stem cells express multiple growth factors that inhibit endothelial cell apoptosis, and demonstrate substantial pulmonary trapping after intravascular delivery.We hypothesized adipose would ameliorate chronic lung injury associated with such as occurring in emphysema.Therapeutic effects of systemically delivered human or mouse adult were evaluated murine models emphysema induced by exposure to cigarette smoke inhibition vascular factor receptors.Adipose detectable the...
Rationale: 17β-Estradiol (E2) attenuates hypoxic pulmonary vasoconstriction and hypertension (HPH) through an unknown mechanism that may involve estrogen receptors (ER) or E2 conversion to catecholestradiols methoxyestradiols with previously unrecognized effects on cardiopulmonary vascular remodeling.Objectives: To determine the by which exerts protective in HPH.Methods: Male rats were exposed hypobaric hypoxia while treated (75 μg/kg/d) vehicle. Subgroups cotreated pharmacologic...
Chronic obstructive pulmonary disease (COPD) occurs in a minority of smokers and is characterized by intermittent exacerbations clinical subphenotypes such as emphysema chronic bronchitis. Although sphingolipids class are implicated the pathogenesis COPD, particular sphingolipid species associated with COPD remain unknown.To use mass spectrometry to determine which plasma COPD.One hundred twenty-nine current former from COPDGene cohort had 69 distinct detected targeted spectrometry. Of...
The epithelial and endothelial cells lining the alveolus form a barrier essential for preservation of lung respiratory function, which is, however, vulnerable to excessive oxidative, inflammatory, apoptotic insults. Whereas profound breaches in this function cause pulmonary edema, more subtle changes may contribute inflammation. mechanisms by cigarette smoke (CS) exposure induce inflammation are not fully understood, but an early alteration has been documented. We sought investigate...
Abstract Circulating endothelial microparticles (EMPs) are emerging as biomarkers of chronic obstructive pulmonary disease (COPD) in individuals exposed to cigarette smoke (CS), but their mechanism release and function remain unknown. We assessed biochemical functional characteristics EMPs circulating (cMPs) released by CS. CS exposure was sufficient increase microparticle levels plasma humans mice supernatants primary human lung microvascular cells. CS-released contained predominantly...
Pulmonary gas exchange relies on a rich capillary network, which, together with alveolar epithelial type I and II cells, form septa, the functional units in lung. Alveolar endothelial cells are critical maintaining structure, because disruption of cell integrity underlies several lung diseases. Here we show that targeted ablation recapitulates cellular events involved cigarette smoke-induced emphysema, one most prevalent nonneoplastic Based phage library screening an immortalized line,...
Abstract Primary graft dysfunction (PGD) is a major complication following lung transplantation. We reported that anti-type V collagen (col(V)) T cell immunity was strongly associated with PGD. However, the role of preformed anti-col(V) Abs and their potential target in PGD are unknown. Col(V) immune serum, purified IgG or B cells from col(V) rats were transferred to WKY rat isograft recipients followed by assessments pathology, cytokines, PaO2/FiO2, an index Immune IgG, all induced...
The molecular events leading to emphysema development include generation of oxidative stress and alveolar cell apoptosis. Oxidative upregulates ceramides, proapoptotic signaling sphingolipids that trigger further space enlargement, as shown in an experimental model due VEGF blockade. As apoptosis mutually interact mediate destruction, we hypothesized the generated by ceramide is required for its pathogenic effect on lung alveoli. To direct effects ceramide, mice received intratracheally...