ORCID Profile
0009-0004-1337-3049
Current Organisations
University of British Columbia
,
The University of British Columbia Centre for Heart Lung Innovation
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Publisher: Cold Spring Harbor Laboratory
Date: 03-03-2023
DOI: 10.1101/2023.03.02.530288
Abstract: Single-cell RNA-sequencing (scRNA-seq) is an important tool for understanding disease pathophysiology, including airways diseases. Currently, the majority of scRNA-seq studies in airways diseases have used invasive methods (airway biopsy, surgical resection) which carry inherent risks and thus present a major limitation to scRNA-seq investigation of airway pathology. Bronchial brushing, where the airway mucosa is s led using a cytological brush, is a viable, less invasive method of obtaining airway cells for scRNA-seq. Here we are describing the development of a rapid and minimal-handling protocol for preparing single cell suspensions from bronchial brush specimens for scRNA-seq. Our optimized protocol maximises cell recovery and cell quality, and may facilitate large-scale profiling of the airway transcriptome at single cell resolution. Single-cell RNA-sequencing (scRNA-seq) measures the gene expression of in idual cells, and may be useful for understanding disease processes. scRNA-seq may be used to investigate lung diseases, but using invasive methods such as biopsy or surgery limits our ability to conduct large research studies. Bronchial brushing, where a soft brush is used to collect cells from inside the lungs, is a safer method but we need a better way to isolate in idual cells from the brush specimens. We developed a method that is faster and involves less handling of the specimens compared to other published methods. Our method may therefore be useful for conducting large scRNA-seq studies in lung diseases.
Publisher: MDPI AG
Date: 15-06-2022
DOI: 10.3390/BIOMEDICINES10061412
Abstract: The associations between airway eosinophilia, measured in sputum or peripheral blood, and acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are inconsistent. We therefore aimed to determine the association between eosinophilia in bronchoalveolar lavage (BAL) fluid and AECOPD in a clinical cohort. We analyzed differential cell counts from baseline BAL fluid in participants in the DISARM clinical trial (Clinicaltrials.gov #NCT02833480) and classified participants by the presence or absence of BAL eosinophilia ( % of total leukocytes). We determined the association between BAL eosinophilia and AECOPD over 1 year of follow-up using negative binomial regression and Cox proportional hazards test. N = 63 participants were randomized, and N = 57 had BAL differential cell counts available. Participants with BAL eosinophilia (N = 21) had a significantly increased rate of acute exacerbations (unadjusted incidence rate ratio (IRR) 2.0, p = 0.048 adjusted IRR 2.24, p = 0.04) and a trend toward greater probability of acute exacerbation (unadjusted hazard ratio (HR) 1.74, p = 0.13 adjusted HR 2.3, p = 0.1) in the year of follow-up compared to participants without BAL eosinophilia (N = 36). These associations were not observed for BAL neutrophilia (N = 41 participants), BAL lymphocytosis (N = 27 participants) or peripheral blood eosinophilia at various threshold definitions (2%, N = 37 3%, N = 27 4%, N = 16). BAL may therefore be a sensitive marker of eosinophilic inflammation in the distal lung and may be of benefit for risk stratification or biomarker-guided therapy in COPD.
Publisher: Elsevier BV
Date: 03-2021
Publisher: Springer Science and Business Media LLC
Date: 14-12-2020
DOI: 10.1038/S41598-020-78818-W
Abstract: Cell entry of SARS-CoV-2, the novel coronavirus causing COVID-19, is facilitated by host cell angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). We aimed to identify and characterize genes that are co-expressed with ACE2 and TMPRSS2 , and to further explore their biological functions and potential as druggable targets. Using the gene expression profiles of 1,038 lung tissue s les, we performed a weighted gene correlation network analysis (WGCNA) to identify modules of co-expressed genes. We explored the biology of co-expressed genes using bioinformatics databases, and identified known drug-gene interactions. ACE2 was in a module of 681 co-expressed genes 10 genes with moderate-high correlation with ACE2 (r 0.3, FDR 0.05) had known interactions with existing drug compounds. TMPRSS2 was in a module of 1,086 co-expressed genes 31 of these genes were enriched in the gene ontology biologic process ‘receptor-mediated endocytosis’, and 52 TMPRSS2- correlated genes had known interactions with drug compounds. Dozens of genes are co-expressed with ACE2 and TMPRSS2 , many of which have plausible links to COVID-19 pathophysiology. Many of the co-expressed genes are potentially targetable with existing drugs, which may accelerate the development of COVID-19 therapeutics.
Publisher: American Thoracic Society
Date: 15-11-2021
Publisher: Springer Science and Business Media LLC
Date: 12-2021
DOI: 10.1186/S12931-021-01911-9
Abstract: Chronic obstructive pulmonary disease (COPD) is an age-related condition that has been associated with early telomere attrition the clinical implications of telomere shortening in COPD are not well known. In this study we aimed to determine the relationship of the epigenetic regulation of telomeric length in peripheral blood with the risk of exacerbations and hospitalization in patients with COPD. Blood DNA methylation profiles were obtained from 292 patients with COPD enrolled in the placebo arm of the Macrolide Azithromycin to Prevent Rapid Worsening of Symptoms Associated with Chronic Obstructive Pulmonary Disease (MACRO) Study and who were followed for 1-year. We calculated telomere length based on DNA methylation markers (DNAmTL) and related this biomarker to the risk of exacerbation and hospitalization and health status (St. George Respiratory Questionnaire [SGRQ]) score over time using a Cox proportional hazards model. We also used linear models to investigate the associations of DNAmTL with the rates of exacerbation and hospitalization (adjusted for chronological age, lung function, race, sex, smoking, body mass index and cell composition). Participants with short DNAmTL demonstrated increased risk of exacerbation ( P = 0.02 ) and hospitalization ( P = 0.03 ) compared to those with longer DNAmTL. DNAmTL age acceleration was associated with higher rates of exacerbation ( P = 1.35 × 10 –04 ) and hospitalization ( P = 5.21 × 10 –03 ) and poor health status (lower SGRQ scores) independent of chronological age ( P = 0.03 ). Telomeric age based on blood DNA methylation is associated with COPD exacerbation and hospitalization and thus a promising biomarker for poor outcomes in COPD.
Publisher: European Respiratory Society (ERS)
Date: 04-2020
Publisher: Wiley
Date: 08-2022
DOI: 10.1002/CLT2.12173
Publisher: Springer Science and Business Media LLC
Date: 19-02-2021
Publisher: MDPI AG
Date: 11-05-2022
DOI: 10.3390/BIOMEDICINES10051110
Abstract: Background: Patients with chronic obstructive pulmonary disease (COPD) are commonly treated with inhaled corticosteroid/long-acting ß2-agonist combination therapy. While previous studies have investigated the host–microbiome interactions in COPD, the effects of specific steroid formulations on this complex cross-talk remain obscure. Methods: We collected and evaluated data from the Study to Investigate the Differential Effects of Inhaled Symbicort and Advair on Lung Microbiota (DISARM), a randomized controlled trial. Bronchoscopy was performed on COPD patients before and after treatment with salmeterol/fluticasone, formoterol/budesonide or formoterol-only. Bronchial brush s les were processed for microbial 16S rRNA gene sequencing and host mRNA sequencing. Longitudinal changes in the microbiome at a community, phylum and genus level were correlated with changes in host gene expression using a Spearman’s rank correlation test. Findings: In COPD patients treated with salmeterol/fluticasone, the expression levels of 676 host genes were significantly correlated to changes in the alpha ersity of the small airways. At a genus level, the expression levels of 122 host genes were significantly related to changes in the relative abundance of Haemophilus. Gene enrichment analyses revealed the enrichment of pathways and biological processes related to innate and adaptive immunity and inflammation. None of these changes were evident in patients treated with formoterol/budesonide or formoterol alone. Interpretation: Changes in the microbiome following salmeterol/fluticasone treatment are related to alterations in the host transcriptome in the small airways of patients with COPD. These data may provide insights into why some COPD patients treated with inhaled corticosteroids may be at an increased risk for airway infection, including pneumonia. Funding: The Canadian Institute of Health Research, the British Columbia Lung Association, and an investigator-initiated grant from AstraZeneca.
Publisher: European Respiratory Society (ERS)
Date: 24-09-2021
Publisher: Elsevier BV
Date: 10-2021
Location: Canada
No related grants have been discovered for Xuan Li.