A5010567054- Chronic Obstructive Pulmonary Disease (COPD) Research
- Neonatal Respiratory Health Research
- Immune cells in cancer
- Cell Adhesion Molecules Research
- Congenital Diaphragmatic Hernia Studies
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Protease and Inhibitor Mechanisms
- Angiogenesis and VEGF in Cancer
- RNA modifications and cancer
- Air Quality and Health Impacts
- MicroRNA in disease regulation
- Cell death mechanisms and regulation
- Heme Oxygenase-1 and Carbon Monoxide
- Autophagy in Disease and Therapy
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Endoplasmic Reticulum Stress and Disease
- Neuroscience of respiration and sleep
- Immunodeficiency and Autoimmune Disorders
- CAR-T cell therapy research
- Blood disorders and treatments
- Asthma and respiratory diseases
- Phagocytosis and Immune Regulation
- Delphi Technique in Research
- Single-cell and spatial transcriptomics
- S100 Proteins and Annexins
University of Pittsburgh
2012-2024
University of Pittsburgh Medical Center
2016-2024
Emmes (United States)
2022
Pulmonary and Allergy Associates
2017-2021
UPMC Montefiore
2021
Grant Medical Center
2017
UPMC Hillman Cancer Center
2011
Washington University in St. Louis
2002-2010
IPF is a progressive lung disorder characterized by fibroblast proliferation and myofibroblast differentiation. Although neutrophil accumulation within lungs has been negatively correlated with outcomes, the role played neutrophils in fibrosis remains poorly understood. We have demonstrated previously that NE promotes cancer cell hypothesized it may similar effect on fibroblasts. In current study, we show NE(-/-) mice are protected from asbestos-induced fibrosis. displayed reduced content...
Matrix metalloproteinases [MMPs] play an important role in extracellular matrix regulation during cell growth and wound healing. Increased expression of MMP-12 [human macrophage elastase] has been reported inflammatory bowel disease [IBD] which is characterised by the loss epithelial tight junction [TJ] barrier function excessive response. The aim this study was to investigate intestinal TJ inflammation. Wild type [WT] MMP-12-/- mice were subjected experimental acute or chronic dextran...
Cigarette smoke (CS) is the most common risk factor for chronic obstructive pulmonary disease (COPD). The present study aimed to elucidate whether mtDNA released upon CS exposure and detected in plasma of former smokers affected by COPD as a possible consequence airway damage. We measured cell-free (cf-mtDNA) nuclear DNA (cf-nDNA) patient mouse serum with CS-induced emphysema. patients mice emphysema showed increased cf-mtDNA levels. In cell culture, sublethal dose CSE decreased...
There is accumulating evidence that delivery of bone marrow cells to sites ischemia by direct local injection or mobilization into the blood can stimulate angiogenesis. This has stimulated tremendous interest in translational potential angiogenic cell population(s) mediate therapeutic However, mechanisms which these angiogenesis are unclear. Herein, we show inflammatory subset monocytes selectively mobilized after surgical induction hindlimb mice and recruited ischemic muscle....
Sepsis and other infections are associated with late cardiovascular events. Although persistent inflammation is implicated, a causal relationship has not been established. We tested whether sepsis causes vascular accelerates atherosclerosis. performed prospective, randomized animal studies at university research laboratory involving adult male ApoE-deficient (ApoE−/−) young C57B/L6 wild-type (WT) mice. In the primary study conducted to determine atherosclerosis, we fed ApoE−/− mice (N = 46)...
Necroptosis has emerged as a potential mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD). Here, we found that markers necroptosis, including high mobility group box 1 release and phosphorylation mixed lineage kinase domain-like protein (p-MLKL), were markedly induced late stage cigarette smoking-induced (CS-induced) emphysema mouse lung tissue well epithelial cells organoids with higher dosage or more prolonged exposure to smoking extract (CSE). Apoptotic signals...
Programmed cell death 1 (PD-1)/programmed ligand (PD-L1) blockade therapy fails in the majority of patients with cancer. Oncolytic viruses represent a new class therapeutic agents, yet efficacy is still disappointing. Moreover, intratumoral injection main approach and preclinical studies mainly employ syngeneic or xenograft models.Use an endogenous mouse lung cancer model that faithfully recapitulates human cancer, various vivo, ex vivo vitro assays, to investigate efficacy, mechanism action...
Cigarette smoke suppresses innate immunity, making smokers more susceptible to infection. The NLRP3 inflammasome is a multi-protein complex that releases interleukin (IL) -1β and IL -18. These cytokines are critical for timely host response pathogens. Whether cigarette affects protein levels, its ability form an inflammasome, not known. Using the human monocyte THP1 cell line C57BL/6 mice, we show decreases levels in cells by increasing ubiquitin-mediated proteasomal processing. Half-life of...
ABSTRACT Airway hydration and ciliary function are critical to airway homeostasis dysregulated in chronic obstructive pulmonary disease (COPD), which is impacted by cigarette smoking has no therapeutic options. We utilized a high-copy cDNA library genetic selection approach the amoeba Dictyostelium discoideum identify protectors smoke. Members of mitochondrial ADP/ATP transporter family adenine nucleotide translocase (ANT) protective against smoke human bronchial epithelial cells. Gene...
One of the most fundamental and challenging questions in field cancer is how immunity transformed from tumor immunosurveillance to tumor-promoting inflammation. Here, we identified suppressor PDZ-LIM domain–containing protein 2 (PDLIM2) as a checkpoint alveolar macrophages (AMs) important for lung suppression. During tumorigenesis, PDLIM2 expression AMs downregulated by ROS-activated transcription repressor BTB CNC homology 1 (BACH1). downregulation leads constitutive activation factor...
Whole lung tissue transcriptomic profiling studies in chronic obstructive pulmonary disease (COPD) have led to the identification of several genes associated with severity airflow limitation and/or presence emphysema, however, cell types driving these gene expression signatures remain unidentified.To determine specific changes severe COPD, we conducted single-cell RNA sequencing (scRNA seq) on n = 29,961 cells from peripheral parenchymal nonsmoking subjects without underlying (n 3) and...
Genetic association studies in chronic obstructive pulmonary disease have primarily tested for with common variants, the results of which explain only a portion heritability. Because rare variation is also likely to contribute susceptibility, we used whole-genome sequencing subjects clinically extreme phenotypes identify genomic regions enriched contributing susceptibility.To genetic emphysema severe airflow obstruction.We identified heavy smokers that were resistant (n = 65) or susceptible...
Abstract Macrophages play a central role in lung physiology and pathology. In this study, we show mice that alveolar macrophages (AMs), unlike other macrophage types (interstitial, peritoneal, splenic macrophages), constitutively express programmed death-1 ligand 1 (PD-L1), thereby possessing superior phagocytic ability the capacity to repress CTLs by cis- trans-interacting with CD80 (PD-1), respectively. This extraordinary of AMs assures optimal protective immunity tolerance within lung....
Abstract For myelodysplastic syndrome (MDS), allogeneic hematopoietic cell transplantation (alloHCT) is the only available curative therapy. The Blood and Marrow Transplant Clinical Trials Network study 1102 (BMT CTN 1102, NCT02016781) was a multicenter, biologic assignment trial based on matched donor availability in adults aged 50–75 with higher risk de novo MDS who were candidates for reduced‐intensity conditioning (RIC) alloHCT. primary analysis showed that those received alloHCT had...
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Pulmonary hypertension (PH) is associated with features of obesity and metabolic syndrome that translate to the induction PH by chronic high-fat diet (HFD) in some inbred mouse strains. We conducted a genome-wide association study (GWAS) identify candidate genes susceptibility HFD-induced PH. Mice from 36 wild-derived strains were fed regular or HFD for 20 weeks beginning at 6-12 age, after which right ventricular (RV) left (LV) end-systolic pressure (ESP) maximum (MaxP) measured cardiac...
Rationale: The role of FSTL-1 (follistatin-like 1) in lung homeostasis is unknown.Objectives: We aimed to define the impact attenuation on structure and function identify FSTL-1-regulated transcriptional pathways lung. Further, we analyze association SNPs with disease.Methods: hypomorphic (FSTL-1 Hypo) mice underwent morphometry, pulmonary testing, micro-computed tomography. Fstl1 expression was determined wild-type cell populations from three independent research groups. RNA sequencing Hypo...