A5078510930- Chronic Obstructive Pulmonary Disease (COPD) Research
- Neonatal Respiratory Health Research
- Delphi Technique in Research
- Congenital Diaphragmatic Hernia Studies
- Asthma and respiratory diseases
- SARS-CoV-2 and COVID-19 Research
- Birth, Development, and Health
- Animal Virus Infections Studies
- Pregnancy and preeclampsia studies
- CRISPR and Genetic Engineering
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- IL-33, ST2, and ILC Pathways
- RNA modifications and cancer
- Single-cell and spatial transcriptomics
- Pediatric health and respiratory diseases
- Machine Learning in Healthcare
- Cancer-related molecular mechanisms research
- Domain Adaptation and Few-Shot Learning
- Prenatal Screening and Diagnostics
- Insect Resistance and Genetics
- AI in cancer detection
- RNA Research and Splicing
- Inflammatory Bowel Disease
- Genetic Associations and Epidemiology
- Respiratory Support and Mechanisms
Wellcome Sanger Institute
2019-2025
Comunidad de Madrid
2024
Universitat de Barcelona
2016-2023
Consorci Institut D'Investigacions Biomediques August Pi I Sunyer
2016-2023
Centro de Investigación Biomédica en Red de Enfermedades Respiratorias
2016-2023
Centro de Investigación Biomédica en Red
2023
Fundació Clínic per a la Recerca Biomèdica
2023
Institute for Research in Biomedicine
2023
Centre for Biomedical Network Research on Rare Diseases
2023
Hospital Clínic de Barcelona
2016-2020
Rationale: Chronic obstructive pulmonary disease (COPD) is characterized by chronic airflow limitation caused a combination of airways (bronchiolitis) and parenchymal destruction (emphysema), whose relative proportion varies from patient to patient.Objectives: To explore contrast the molecular pathogenesis emphysema bronchiolitis in COPD.Methods: We used network analysis lung transcriptomics (Affymetrix arrays) 70 former smokers with COPD compare differential expression gene coexpression...
Background. Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous condition. We hypothesized that the unbiased integration of different COPD lung omics using novel multi-layer approach may unravel mechanisms associated with clinical characteristics. Methods. profiled mRNA, miRNA and methylome in tissue samples from 135 former smokers COPD. For each omic (layer) we built patient network based on molecular similarity. The three networks were used to build network, optimization...
Patients with chronic obstructive pulmonary disease (COPD) often suffer episodes of exacerbation (ECOPD) that impact negatively the course their disease. ECOPD are heterogeneous events unclear pathobiology and non-specific diagnosis. Network analysis is a novel research approach can help unravelling complex biological systems. We hypothesised comparison multi-level ( i.e. , clinical, physiological, biological, imaging microbiological) correlation networks determined during convalescence...
Chronic Obstructive Pulmonary Disease (COPD) is associated with an abnormal pulmonary and systemic immune response to tobacco smoking. Yet, how do cells relate within between these two biological compartments, the infiltrate influences lung transcriptome, what role of active smoking vs. presence disease unclear. To investigate questions, we simultaneously collected tissue blood from 65 individuals stratified by habit disease. The cell composition both tissues was assessed flow cytometry,...
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 screens based on CRISPR/Cas technology are a powerful tool for understanding cellular phenotypes. However, the coverage and replicate requirements result in large experiment sizes, which limiting when samples scarce, or protocols expensive laborious. Here, we present an approach to reduce scale of genome-wide perturbation up fivefold without sacrificing performance. To do so, deliver two randomly paired gRNAs into each cell, rely recent advances gRNA design, as well availability...
Tobacco smoking is the main environmental risk factor for chronic obstructive pulmonary disease (COPD), but not all smokers develop disease. A population of lung-resident mesenchymal stem cells (LR-MSCs) exist in healthy lungs, how tobacco affects them and their role COPD have been assessed yet. Using a sphere-based culture technique, we isolated LR-MSCs from lung tissue obtained nonsmokers current former with without (n = 53). The were characterized by flow cytometry Affymetrix arrays....
Summary The biological mechanisms through which most non-protein-coding genetic variants affect disease risk are unknown. To investigate the gene-regulatory cascades that ensue from these variants, we mapped blood gene expression and splicing quantitative trait loci (QTLs) bulk RNA-sequencing in 4,732 participants, integrated data with protein, metabolite lipid QTLs same individuals. We identified cis -QTLs for of 17,233 genes 29,514 events (in 6,853 genes). Using colocalization analysis,...
Perturbing expression is a powerful way to understand the role of individual genes, but can be challenging in important models. CRISPR-Cas screens human induced pluripotent stem cells (iPSCs) are limited efficiency due DNA break-induced stress, while less stressful silencing with an inactive Cas9 has been considered effective so far. Here, we developed dCas9-KRAB-MeCP2 fusion protein for screening iPSCs from multiple donors. We found 200 bp window around transcription start site polyclonal...
Summary Crohn’s disease (CD) is a complex inflammatory disorder of incompletely understood molecular aetiology. We generated large single-cell RNA sequencing dataset from the terminal ileal biopsies two independent cohorts comprising total 50 CD patients and 71 healthy controls. performed transcriptomic analyses to reveal genes, cell types mechanisms perturbed in CD, leveraging power confirm our findings assess replicability. In addition mapping widespread alterations cytokine signalling, we...
Bone marrow (BM) produces hematopoietic and progenitor cells that contribute to distant organ inflammation repair. Chronic obstructive pulmonary disease (COPD) is characterized by defective lung Yet, BM composition has not been previously in COPD patients. In this prospective controlled study, was obtained sternum fine-needle aspiration 35 patients 25 healthy controls (10 smokers 15 never-smokers). cell count immunophenotype were determined microscopy flow cytometry, respectively....
Fetal growth restriction (FGR) affects 5-10% of pregnancies, is the largest contributor to fetal death, and can have long-term consequences for child. Implementation a standard clinical classification system hampered by multiphenotypic spectrum small fetuses with substantial differences in perinatal risks. Machine learning multiomics data potentially revolutionize decision-making FGR identifying new phenotypes. Herein, we describe cluster analysis based on an unbiased machine-learning...
The natural history of chronic obstructive pulmonary disease (COPD) is still not well understood. Traditionally believed to be a self-inflicted by smoking, now we know that all smokers develop COPD, other inhaled pollutants different from cigarette smoke can also cause it, and abnormal lung development lead COPD in adulthood. Likewise, the inflammatory response characterizes varies significantly between patients, them perceive symptoms (mostly breathlessness) similarly. To investigate...
Abstract Background The role of the immune system in pathobiology Idiopathic Pulmonary Fibrosis (IPF) is controversial. Methods To investigate it, we calculated signatures with Gene Set Variation Analysis (GSVA) and applied them to lung transcriptome followed by unbiased cluster analysis GSVA immune-enrichment scores, 109 IPF patients from Lung Tissue Research Consortium (LTRC). Results were validated experimentally using cell-based methods (flow cytometry) tissue University Pittsburgh (n =...
<b>Rationale:</b> COPD is characterized by an abnormal immune response to tobacco smoke, both in the lungs and circulating blood, which not fully understood. Whether or pulmonary systemic inflammation are related also unclear. <b>Objectives:</b> To characterize contrast patients (current smokers=31; former smokers=17) healthy controls (ever smokers, n=15 non-smokers, n=13). <b>Methods:</b> Non-tumoral lung tissue blood were obtained from individuals undergoing resectional surgery, mostly...
<b>Introduction:</b> COPD is related to increased risk for the development of lung cancer, which an important cause death in these patients. <b>Objectives:</b> The primary objective was identify transcripts associated pathogenesis cancer <b>Methods:</b> We recruited 20 patients undergoing bronchoscopy, 10 with and withouth cancer. In transcriptomic profile obtained both from tumoral non adjancent tissue. whole determined by next generation sequencing analized using standard bioconductor...
<b>Background:</b> GOLD 2017 proposed not to consider airflow limitation (FEV1) stratify COPD patients in order guide their pharmacological treatment. <b>Objective:</b> To investigate the temporal stability (3 years follow-up) and association with all-cause mortality of four groups (A-D) as compared that 2011. <b>Methods:</b> We used ECLIPSE cohort these questions. <b>Results:</b> found 2017: (1) increased proportion A B (from 24 39% from 14 39%, respectively), a parallel decrease C D 23 7%...
<b>Rationale:</b> Patients with chronic obstructive pulmonary disease (COPD) often suffer episodes of exacerbation (ECOPD) that impact negatively the course their disease. We hypothesized comparison multi-level (i.e., clinical, biological, imaging and microbiological) correlation networks during ECOPD at clinical recovery can yield useful pathogenic information. <b>Aims:</b> To describe weight interactions among different network components ECOPD. <b>Methods:</b> In a multicenter study in...
<b>Background</b> Chronic Obstructive Pulmonary Disease (COPD) is characterized by pulmonary and systemic manifestations. Multiple studies have identified airway or blood biomarkers associated with the severity of airflow limitation, but it not clear whether these directly represent pathobiology in lung. <b>Objective</b> To identify pathobiological mechanisms shared between different compartments COPD patients. <b>Methods</b> Weighted Gene Co-expression Network Analysis (WGCNA) was used to...