The Cysteinyl Leukotriene E4 Receptor, GPR99, Orchestrates Airway Epithelial Cell Differentiation and Type 2 Pulmonary Inflammation

半胱氨酰白三烯 E4 受体 GPR99 协调气道上皮细胞分化和 2 型肺部炎症

• 批准号: 9371062
• 负责人: Lora Bankova
• 金额: $ 19.98万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9371062
• 关键词: Affinity; Allergens; Allergic Disease; Alternaria; Aspirin; Asthma; Automobile Driving; Award; Basophils; Bioinformatics; Biology; Breathing; Bronchoconstriction; Brush Cell; Cell Count; Cell Differentiation process; Cell physiology; Cells; Complement; Data; Development; Development Plans; Disease; Environment; Eosinophilia; Epithelial; Epithelial Cells; Event; Five-Year Plans; Funding; Future; Generations; Genes; Genetic Transcription; Genomics; Goals; Goblet Cells; Grant; Hospitals; Human; Hypersensitivity; Imaging Techniques; Immune; Immunity; Immunology; Inflammation; Inflammatory Response; Interleukin-13; Intestines; Knowledge; Laboratories; Lead; Leadership; Leukotriene E4; Light; Liquid substance; Lung; Lung Inflammation; Lymphoid Cell; Mediating; Mediator of activation protein; Mentorship; Metaplasia; Methods; Modeling; Molds; Molecular; Mucins; Mucous Membrane; Mus; Nose; Obstruction; Patients; Pharmacology; Physicians; Population; Positioning Attribute; Process; Production; Pulmonary Inflammation; Recruitment Activity; Reporter; Reporting; Research; Research Personnel; Resistance; Resources; Role; Scientist; Secure; Severities; Signal Transduction; Source; Structure of mucous membrane of nose; Surface; Systems Biology; TSLP gene; Techniques; Testing; Therapeutic; Time; Tissues; Training; Translational Research; United States National Institutes of Health; Up-Regulation; Update; Virus; Woman; Work; Writing; airborne allergen; airway inflammation; airway remodeling; aspirin-exacerbated respiratory disease; career; career development; cell type; curriculum development; cysteinyl-leukotriene; didactic education; disorder control; eosinophil; feeding; gut microbiota; inhibitor/antagonist; mast cell; mucosal site; novel; profiles in patients; receptor; research and development; respiratory; response; responsible research conduct; skills; transcription factor; transcriptome; transcriptome sequencing; translational research program

PROJECT SUMMARY/ABSTRACT: This proposal details a five-year plan to provide the candidate, Lora Bankova, MD, with the knowledge and expertise to become an independent investigator in the field of Allergy and Immunology. The studies focus on a previously unrecognized role of the stable cysteinyl leukotriene (cysLT) metabolite LTE4 in the control of proximal events leading to development of type 2 immunity to the outdoor mold aeroallergen, Alternaria. Using a combination of cellular and molecular approaches, the candidate will test the hypothesis that GPR99 drives innate type 2 immunity and airway remodeling through the control of epithelial cell activation for IL-25 generation. As LTE4 is the only stable cysLT metabolite and is detected in asthma elicited by allergen, viruses, aspirin, there are significant translational implications for asthma. The short-term goals of this K08 award application are to provide training in advanced imaging techniques, advanced genomic techniques, including RNA-Seq, and human translational research. Dr. Bankova's long-term goal is to develop an independent translational research program studying the innate immune control of allergic disease. During the period of support the candidate will complement her laboratory skills with didactic coursework to develop skills in emerging gene sequencing and editing methods, courses in bioinformatics and systems biology, grant writing, leadership, and the responsible conduct of research germane to the application. This will then facilitate her transition to independence during the third and fourth years of the award. Dr. Bankova will work under the mentorship of Nora Barrett, MD and Joshua Boyce, MD, experts in cysLT biology and mechanisms of inflammation. Dr. Bankova has also assembled a team of extraordinary scientists, including Drs. Yoshihide Kanaoka, Carla Kim, Bruce Levy, Howard Katz, and K. Frank Austen, who have committed their time, resources, and expertise to facilitate her career development and research goals. Under their mentorship and guidance, in an ideal scientific environment at the Brigham and Women's Hospital, training in immunology, didactic curriculum, and career development plan will position the candidate to secure independent NIH funding and to establish herself as a physician scientist with a focus on the role of mast cells and cysLTs in instructing epithelial cell activation to guide immune bias at mucosal surfaces.

项目总结/文摘: