Innate Signaling, Cysteinyl Leukotrienes, and Asthma Elicited by House Dust Mite

先天信号传导、半胱氨酰白三烯和屋尘螨引发的哮喘

• 批准号: 7932080
• 负责人: Nora Amanda Barrett
• 金额: $ 13.65万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-14 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7932080
• 关键词: Allergens; Allergic; Allergic Disease; Allergic inflammation; Antigen-Presenting Cells; Antigens; Asthma; Basic Science; Biology; Bone Marrow; Breathing; C Type Lectin Receptors; Cell physiology; Cells; Commit; Consult; Data; Dendritic Cells; Dendritic cell activation; Dermatophagoides farinae; Dermatophagoides pteronyssinus; Development; Eicosanoids; Epidemiology; Event; Exposure to; Fellowship; Generations; Hospitals; Hypersensitivity; Immune response; Immunology; In Vitro; Individual; Inflammation; Inflammation Mediators; Inflammatory; Institution; Instruction; Laboratories; Link; Lung; Mediating; Mediator of activation protein; Medicine; Mentors; Modeling; Molecular; Molecular Biology; Mononuclear; Mus; Myelogenous; Pathogenesis; Pattern; Pattern recognition receptor; Pneumonia; Polysaccharides; Preparation; Principal Investigator; Process; Production; Program Development; Prostaglandins; Protocols documentation; Pyroglyphidae; Receptor Signaling; Recruitment Activity; Research; Research Personnel; Resources; Risk Factors; Role; Scientist; Series; Signal Transduction; Source; Stimulus; T cell response; T-Cell Activation; Testing; Training; Training Programs; Woman; Work; airborne allergen; asthma prevention; career; chemokine; cysteinyl-leukotriene; cytokine; design; eosinophil; immunogenic; in vivo; instructor; leukotriene-C4 synthase; lipid mediator; mast cell; microbial; mouse dectin-2; mouse model; neutrophil; novel; pathogen; programs; pyroglyphid; receptor; response; skills

DESCRIPTION (provided by applicant): This proposal details a 5-year training program for the development of an academic career in the pathogenesis of asthma and allergic inflammation. The PI will focus her efforts on acquiring critical skills in molecular biology and mouse models of asthma to become an independent investigator. The PI completed fellowships in Pulmonary and in Allergy and Immunology at Brigham and Women's Hospital, including two years of research on the role of cysteinyl leukotrienes (cys-LTs) as powerful pro-inflammatory mediators. She is now an Instructor in Medicine with plans to continue basic science research under the direction of Dr. Frank Austen (mentor) and Dr. Yoshihide Kanaoka (co-mentor). Dust mite is one of the most significant allergens world-wide and has been linked to asthma pathogenesis. Recent work in Dr. Austen's lab shows that glycans in house dust mite extract elicit robust production of cys-LTs, and that the myeloid C-type lectin receptor, Dectin-2, mediates this process. This work describes a novel mechanism by which allergens can promote inflammation and identifies an important function for this newly-described pattern-recognition receptor. In the proposed plan, we will investigate the role of Dectin-2 signaling, and the subsequent cys-LTs produced, in dendritic cell activation (Aim 1) and in the generation of innate and adaptive pulmonary inflammation (Aim 2) in response to dust mite. The mentor is an eminent scientist in the field with over 50 established trainees and is fully focused on his current laboratory program. The co-mentor is an established molecular biologist who will directly supervise the trainee. In addition, an advisory group includes experts in pattern recognition receptors (Dr. Kobayashi) and eicosanoid biology (Dr. Boyce). Dr. Lambrecht, an expert in mouse models of dendritic cell function in asthma, will consult. The research will take place within the highly collaborative Inflammation and Allergic Diseases Research Section, a source of additional support. Lastly, the institution is committed to providing the necessary resources and training to help the primary investigator establish an independent career. RELEVANCE (See instructions): House dust mite is one of the most significant causes of allergy worldwide, and this allergy is a risk factor for the development of asthma. Studies to determine why this house dust mite is so immunogenic will be helpful to design new therapies for asthma prevention and treatment.

描述（由申请人提供）：本提案详细介绍了哮喘和过敏性炎症发病机理的学术生涯发展的5年培训计划。PI将专注于获得分子生物学和哮喘小鼠模型的关键技能，成为一名独立的研究者。她在布莱根妇女医院（Brigham and Women's Hospital）完成了肺部和过敏与免疫学的研究，包括对半胱氨酸白三烯（cys- lt）作为强效促炎介质的作用进行了两年的研究。她现在是一名医学讲师，并计划在Frank Austen博士（导师）和Yoshihide Kanaoka博士（共同导师）的指导下继续进行基础科学研究。