Macrophage Pathogen Interactions in Regional Cystic Fibrosis Lung Inflammation

巨噬细胞病原体在局部囊性纤维化肺部炎症中的相互作用

• 批准号: 10630960
• 负责人: ALIX ASHARE
• 金额: $ 10.7万
• 依托单位: DARTMOUTH-HITCHCOCK CLINIC
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10630960
• 关键词: Advisory Committees; Award; Bronchiectasis; Cells; Clinical; Clinical Medicine; Clinical Research; Cystic Fibrosis; Data; Development; Disease; Doctor of Philosophy; Environment; Exhibits; Frequencies; Funding; Generations; Genotype; Glycolysis; Goals; Heterogeneity; Hypoxia; Immune; Immune response; Individual; Infection; Inflammation; Inflammatory; Inflammatory Response; Investigation; Junior Physician; Knowledge; Lead; Lobe; Lung; Lung diseases; Macrophage; Mentors; Metabolic; Metabolism; Mission; Mucous body substance; Mutation; Pathogenesis; Phagocytosis; Phenotype; Physicians; Population; Production; Pseudomonas aeruginosa; Public Health; Publishing; Pulmonary Cystic Fibrosis; Pulmonary Inflammation; Research; Research Project Grants; Respiratory Failure; Role; Scientist; Succinates; Testing; Time; Translational Research; United States National Institutes of Health; Virulence; Virulence Factors; Work; adaptive immune response; chemokine; chronic infection; cystic fibrosis infection; cystic fibrosis patients; cytokine; extracellular; human disease; human subject; improved; inflammatory lung disease; innovation; lung lobe; lung upper lobe; metabolic profile; microbiota; neutrophil; novel therapeutic intervention; pathogen; patient oriented; patient oriented research; pediatric patients; programs; recruit; regional difference; response; skills; time use; transcription factor; translational study

ABSTRACT The goal of this K24 is to provide support to allow Dr. Ashare to spend an additional 25% of her time mentoring junior physician scientists in patient-oriented research on inflammatory lung disease. This K24 will provide the opportunity for Dr. Ashare to expand her program in patient- oriented translational research, integrate new physician scientists and PhD scientists into her research program, and allow for additional protected time so she can mentor additional trainees. In addition, with the help of her senior advisory committee, she will also use this time to improve her own mentoring skills. This K24 describes two aims that involve patient-oriented translational research using primary lung macrophages obtained from human subjects. Each Aim will serve as an individual project for a new trainee. Aim1 exploits preliminary findings that macrophages isolated from different regions of the lung are metabolically different and will specifically investigate the impact of increased glycolytic metabolism in upper lobe macrophages on the generation of inflammation. This aim will also determine the role of succinate accumulation in the generation of the macrophage inflammatory response. Based upon our data demonstrating that there are phenotypic and genotypic differences in Pseudomonas aeruginosa isolates from different regions of the CF lung, Aim 2 will test the hypothesis that regional P. aeruginosa isolates differentially stimulate lung macrophage immune responses and exhibit different responses to extracellular succinate. These two independent but complementary aims will allow new trainees to pursue translational patient-oriented research projects that will lead to a greater understanding of host-pathogen interactions in the CF lung.

抽象的 这款K24的目标是提供支持，以允许Ashare博士多花25％ 指导初级医师科学家从事炎症性肺的研究 疾病。这款K24将为Ashare博士提供机会扩大其患者计划的机会 - 定向转化研究，将新的医师科学家和博士学位科学家纳入她 研究计划，并允许更多受保护的时间，以便她可以指导其他学员。 此外，在她的高级咨询委员会的帮助下，她还将利用这段时间来改善 她自己的指导技巧。该K24描述了涉及以患者为导向的翻译的两个目标 使用从人类受试者获得的原发性肺巨噬细胞的研究。每个目标都将服务 作为新学员的个人项目。 AIM1利用巨噬细胞的初步发现 从肺的不同区域分离出来的是代谢不同的，并且会特别 研究上叶巨噬细胞中糖酵解代谢增加的影响 发炎产生。这个目标还将决定琥珀酸酯在 巨噬细胞炎症反应的产生。根据我们的数据证明 从铜绿假单胞菌分离株中存在表型和基因型差异 CF肺的不同区域，AIM 2将检验以下假设：铜绿假单胞菌 分离物差异刺激肺巨噬细胞免疫反应，并表现出不同的 对细胞外琥珀酸酯的反应。这两个独立但互补的目标将允许 新学员追求转化的以患者为导向的研究项目，这将导致更大的 了解CF肺中宿主 - 病原体相互作用。

项目成果

The Impact of Chronic Electronic Cigarette Use on Alveolar Macrophage Lipid Content: Case Report.

长期使用电子烟对肺泡巨噬细胞脂质含量的影响：病例报告。

• DOI: 10.26502/acmcr.96550545
• 发表时间: 2022
• 期刊: Archives of clinical and medical case reports
• 作者: Ruttenberg,Molly;Armstrong,David;Mellinger,Diane;Carroll,James;Ashare,Alix
• 通讯作者: Ashare,Alix

P. aeruginosa tRNA-fMet halves secreted in outer membrane vesicles suppress lung inflammation in Cystic Fibrosis.

外膜囊泡中分泌的铜绿假单胞菌 tRNA-fMet 一半可抑制囊性纤维化中的肺部炎症。

• DOI: 10.1101/2024.02.03.578737
• 发表时间: 2024
• 期刊: bioRxiv : the preprint server for biology
• 作者: Li,Zhongyou;Barnaby,Roxanna;Nymon,Amanda;Roche,Carolyn;Koeppen,Katja;Ashare,Alix;Hogan,DeborahA;Gerber,ScottA;Taatjes,DouglasJ;Hampton,ThomasH;Stanton,BruceA
• 通讯作者: Stanton,BruceA