Defining neutrophil functional heterogeneity & dysfunction in COPD using single cell proteomics
Ente: WT
Scadenza: 2031-03-01
Importo max: 831.818 EUR
Paese: EU
Descrizione
Neutrophils are vital innate immune cells. Recent work has detailed their transcriptional heterogeneity related maturity and tissue residency. However, neutrophils display a pronounced discordance between mRNA and protein abundance, making proteomics a highly valuable technique to study them. Neutrophils play essential roles in Chronic obstructive pulmonary disease (COPD), a disease which is the third leading cause of death in adults >50 years old. I propose that pathogenic neutrophil subsets drive disease onset and progression. In this proposal I will leverage mini-bulk and single cell proteomic approaches combined with analytics pipelines to study neutrophil populations and functional states across the bone marrow, blood and airways in healthy controls, healthy smokers and COPD patients. This will enable me to define the differences of neutrophil phenotypes across tissues, delineating changes specific to the airways compared to those centrally programmed in the bone marrow. It will also enable a comparison of COPD to healthy volunteers and healthy smokers, determining phenotypes exclusive to patients with established airway disease and those shared with healthy smokers.This proposal will significantly expand our understanding of neutrophil diversity and function in COPD, empowering the discovery of phenotypes and populations that can be targeted to improve patient outcomes.
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