Identification of stage and cell specific cellular and gene regulatory networks involved in the progression of idiopathic pulmonary fibrosis

鉴定参与特发性肺纤维化进展的阶段和细胞特异性细胞和基因调控网络

基本信息

项目摘要

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.
特发性肺纤维化(IPF)是一种进行性的人类肺部纤维化疾病,没有确定的致病因素。受IPF影响的个体通常会发生进行性肺功能丧失,伴有生活质量严重下降,可用的治疗选择有限,并且没有一种治疗方法。通常,IPF患者的准确诊断是困难的,因为临床表现可能是可变的,并且不存在分子诊断参数。IPF的病理生理学特征是肺成纤维细胞响应衰老气道上皮细胞指示的修复回路故障而发生异常胶原沉积。衰老气道上皮细胞的清除和组织修复机制的协调受到组织驻留和募集的单核吞噬细胞的严格调节。因此,了解单核吞噬细胞在IPF进展和调节中的作用至关重要。为了揭示人单核吞噬细胞在IPF进展和分子病理学中的作用以及评估其诊断潜力,我们建议研究诊断为轻度、中度或重度IPF的个体的支气管肺泡免疫细胞区室。利用最先进的单细胞技术,如单细胞转录组学和高维流式细胞术,我们将评估疾病阶段和细胞区室特异性分子网络,并确定纤维化进展和疾病严重程度的新决定因素,这反过来又将与临床参数相关联,以帮助诊断。接下来,我们将选择具有最大预测潜力的分子,并将开发临床适用的流式细胞术方法,以预测疾病进展并改善阶段特异性诊断。总体而言,该提案旨在以细胞类型特异性方式鉴定IPF进展和严重程度的新型分子决定因素,从而能够鉴定新型生物标志物和治疗靶点,以个性化和改善IPF的治疗和诊断。

项目成果

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Professor Dr. Andreas Schlitzer其他文献

Professor Dr. Andreas Schlitzer的其他文献

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{{ truncateString('Professor Dr. Andreas Schlitzer', 18)}}的其他基金

Understanding the role of Gpr183 for the development and function of murine lung resident dendritic cells
了解 Gpr183 对小鼠肺常驻树突状细胞发育和功能的作用
  • 批准号:
    440241727
  • 财政年份:
    2020
  • 资助金额:
    --
  • 项目类别:
    Research Grants
The impact of transcriptomic imprinting on the functional specialization of monocytes during health and disease
转录组印记对健康和疾病期间单核细胞功能特化的影响
  • 批准号:
    282795005
  • 财政年份:
    2016
  • 资助金额:
    --
  • 项目类别:
    Independent Junior Research Groups

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    10697370
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    2022
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癌症特异性 T 细胞的抗原独立预测和生物标志物鉴定
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诊断时鉴定致命性黑色素瘤
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星形胶质细胞-肿瘤串扰调节脑转移瘤的系统鉴定
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Identification of early stage malignancy changes in the structural and biophysical proporties of exosomes by atomic force microscopy (AFM)-based nano-mechanical measurements
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癌症特异性 T 细胞的抗原独立预测和生物标志物鉴定
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Identification of Lethal Melanomas at the Time of Diagnosis
诊断时鉴定致命性黑色素瘤
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    10589941
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Antigen-independent prediction and biomarker identification of cancer-specific T cells
癌症特异性 T 细胞的抗原独立预测和生物标志物鉴定
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