Project Details
Projekt
Identification of stage and cell specific cellular and gene regulatory networks involved in the progression of idiopathic pulmonary fibrosis
Subject Area
Pneumology, Thoracic Surgery
Immunology
Immunology
Term
since 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 458958013
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing disorder of the human lung, with no causative factors identified. Individuals affected by IPF often undergo a progressive loss of lung function accompanied by a severe decline in the quality of life, with limited treatment of options available and none of them being curative. Often an accurate diagnosis of IPF patients is difficult as the clinical presentation can be variable and molecular diagnosis parameters do not exist. Pathophysiologically IPF is characterized by aberrant collagen deposition by pulmonary fibroblasts in response to malfunctioning repair circuits instructed by senescent airway epithelial cells. The clearance of senescent airway epithelial cells and orchestration of tissue repair mechanisms is tightly regulated by tissue-resident and recruited mononuclear phagocytes. Therefore it is crucial to understand the role of mononuclear phagocytes in the progression and regulation of IPF. To reveal the role of human mononuclear phagocytes for the progression and molecular pathology of IPF as well as to gauge their diagnostic potential, we propose to investigate the bronchoalveolar immune cell compartment of individuals diagnosed either with mild, moderate, or severe IPF. Utilizing state of the art single-cell technologies, such as single-cell transcriptomics and high dimensional flow cytometry we will assess the disease stage and cellular compartment-specific molecular networks and identify novel determinants of fibrosis progression and disease severity, which in turn will be linked to clinical parameters to aid diagnosis. Next, we will select the molecules which harbor the greatest predictive potential and will develop a clinically applicable flow cytometry approach in order to predict disease progression and to improve stage-specific diagnosis. Collectively this proposal aims to identify novel molecular determinants of IPF progression and severity in a cell type-specific manner, enabling identification of novel biomarkers and therapeutic targets to personalize and improve treatment and diagnosis of IPF.
DFG Programme
Research Grants
