Project description:To profile lung miRNA expression in our mouse model of cigarette smoke-induced chronic obstructive pulmonary disease, we employed the Agilent unrestricted Mouse miRNA (8 x 15k arrays per slide, AMADID Number: 021828, Sanger Version 12) platform as a discovery tool to identify miRNAs of interest in the development of experimental chronic obstructive pulmonary disease. Mice were exposed to cigarette smoke (or room air) for 4, 6, 8, 12 weeks, lungs were excised, and total RNA isolated.
2021-11-05 | GSE186955 | GEO
Project description:WGS of Pseudomonas strains isolated from Jordan
Project description:Chronic myeloid leukemia (CML) epitomizes successful targeted therapy, with 86% of patients in the chronic phase treated with tyrosine kinase inhibitors (TKIs) attaining remission. However, resistance to TKIs occurs during treatment, and patients with resistance to TKIs progress to the acute phase called Blast Crisis (BC), wherein the survival is restricted to 7-11 months. About 80 % of patients in BC are unresponsive to TKIs. This issue can be addressed by identifying a molecular signature which can predict resistance in CML-CP prior to treatment as well as by delineating the molecular mechanism underlying resistance. Herein, we report genomic analysis of CML patients and imatinib-resistant K562 cell line to achieve the same. WGS was performed on imatinib-sensitive and -resistant K562 cells. Library preparation was done by 30x WGS KAPA PCR-Free v2.1 kit, and Illumina HiSeq X sequencer was used for 2 x 150 bp paired-end sequencing. Our study identified accumulation of aberrations on chromosomes 1, 3, 7, 16 and 22 as predictive of occurrence of resistance. Further, recurrent amplification in chromosomal region 8q11.2-12.1 was detected in highly resistant K562 cells as well as CML patients. The genes present in this region were analyzed to understand molecular mechanism of imatinib resistance.
Project description:This project is about an untargeted metabolomic analysis in samples that come from chronic lung allograft dysfunction disease patients.
Project description:Bronchopulmonary dysplasia (BPD) is a chronic lung disease of prematurity. Exposure to noxious stimuli such as hyperoxia, volutrauma, and infection in infancy can have long-reaching impacts on lung health and predispose towards the development of conditions such as chronic obstructive pulmonary disease (COPD) in adulthood. BPD and COPD are both marked by lung tissue degradation, neutrophil influx, and decreased lung function. Both diseases also express a change in microbial signature characterized by firmicute depletion. However, the relationship between pulmonary bacteria and the mechanisms of downstream disease development has yet to be elucidated. We hypothesized that murine models of BPD would show heightened acetylated proline-glycine-proline (Ac-PGP) pathway and neutrophil activity, and through gain- and loss-of-function studies we show that Ac-PGP plays a critical role in driving BPD development. We further test a inhaled live biotherapeutic (LBP) using active Lactobacillus strains in in vitro and in vivo models of BPD and COPD. The Lactobacillus-based LBP is effective in improving lung structure and function, mitigating neutrophil influx, and reducing a broad swath of pro-inflammatory markers in these models of chronic pulmonary disease via the MMP-9/PGP (matrix metalloproteinase/proline-glycine-proline) pathway. Inhaled LBPs show promise in addressing common pathways of disease progression that in the future can be targeted in a variety of chronic lung diseases.
Project description:Pseudomonas aeruginosa chronically colonizes the lungs of individuals with CF, where it reaches high cell densities and produces a battery of virulence factors. Upon infection, a single strain of P. aeruginosa can colonize an individualâs lungs throughout his or her lifetime. To understand the evolution of P. aeruginosa during chronic lung infection, we conducted both genotypic and phenotypic analyses on clinical isogenic strains obtained from the lungs of three different individuals with CF. These strains were isolated over a period of approximately ten years and possess phenotypes that are commonly observed in isolates from the CF lung, such as the antibiotic resistant dwarf and mucoid phenotypes. Microarray analyses were carried out on isolates grown in a chemically defined medium that mimics the nutritional environment of the CF lung, synthetic CF sputum medium (SCFM). 17 clinically isolated P. aeruginosa strains from three individuals with CF (5 strains from individual P1, 7 strains from individual P2, 5 strains from individual P3). Two reference strains PAO1 and PA14. All experiments were biologically duplicated.
Project description:A shaving proteomic approach was applied to explore surface protein expression of multi- and pan-drug resistant strains of Pseudomonas aeruginosa isolated from the airways of cystic fibrosis patients with long-term chronic colonization compared to wild-type antibiotic-sensitive strains isolated from patients with recent infection.
Project description:For this project, we explored the genetic determinants of the heart development condition termed patent foramen ovale (PFO) using quantitative trait loci (QTL) mapping and genomics/transcriptomics analyses. Two mice strains were chosen that exhibit highly divergent phenotypes associated with PFO, 129T2/SvEms and QSi5. In this experiment, we performed whole genome sequencing (WGS) on genomic DNA extracted from liver specimens of 129T2/SvEms or QSi5 mice in order to identify genomic variants that may contribute to the phenotypes associated with PFO.