Role for B-cell mediated olfactory loss in Chronic Sinusitis with Nasal Polyps

B 细胞介导的嗅觉丧失在慢性鼻窦炎伴鼻息肉中的作用

• 批准号: 8586309
• 负责人: Bruce K Tan
• 金额: $ 22.88万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-12-15 至 2016-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8586309
• 关键词: Accounting; Affect; Anatomy; Antigens; Autoantibodies; Autoimmune Process; Autoimmunity; Automobile Driving; Award; B-Cell Activation; B-Lymphocytes; Biological Assay; Biometry; Blood Vessels; Cell Maturation; Chronic Sinusitis; Clinical; Color; Complement; Data; Deposition; Development; Diagnostic tests; Disease; Drug or chemical Tissue Distribution; Enzyme-Linked Immunosorbent Assay; Epithelial; Epithelium; Equipment and supply inventories; Fibroblasts; Flow Cytometry; Functional disorder; Future; Generations; Grant; Head and Neck Surgery; Histological Techniques; IL6 gene; Immunofluorescence Immunologic; Immunoglobulin A; Immunoglobulin Class Switching; Immunoglobulin G; Immunology; Impairment; Inferior nasal concha; Infiltration; Inflammation; Inflammatory; Investigation; Irrigation; K-Series Research Career Programs; Laboratories; MS4A1 gene; Mediating; Medical; Mentors; Mentorship; Molecular; Nasal Polyps; Nasal turbinate bone structure; Neurons; Nose; Olfactory Mucosa; Operative Surgical Procedures; Otolaryngology; Pathogenesis; Pathogenicity; Patients; Plasma Cells; Platelet-Derived Growth Factor Receptor; Play; Population; Recovery; Regression Analysis; Research Design; Research Personnel; Resistance; Risk Factors; Role; Serum; Sinus; Smell Perception; Structure of mucous membrane of nose; Symptoms; Testing; Therapeutic; Therapeutic Agents; Time; Tissues; Training; Universities; age related; base; career; chemokine; chronic rhinosinusitis; clinical practice; cytokine; density; eosinophil; improved; medical schools; molecular marker; mouse model; neuron loss; olfactory threshold; overexpression; plasma cell differentiation; professor

DESCRIPTION (provided by applicant): Dr. Bruce K. Tan is an Assistant Professor in the Department of Otolaryngology-Head and Neck Surgery at the Northwestern University Feinberg School of Medicine where his clinical practice is dedicated to rhinolology and olfactory loss. This career development award, under the mentorship of Drs. Robert P. Schleimer and Jay A. Gottfried, is focused on understanding the impact of B-cell mediated inflammation on the pathogenesis and olfactory loss associated with Chronic Sinusitis with Nasal Polyps (CRSwNP). CRSwNP is a prevalent inflammatory condition of the nose and paranasal sinuses that is a major cause of acquired olfactory loss. Currently, the inflammatory mechanisms driving this disease are poorly understood, thus limiting the classes of therapeutic agents utilized to treat this disease. We have increasing evidence and further preliminary data showing that B-cell inflammation and autoimmunity is present within some nasal polyps and may play an important role in the persistent inflammation associated with CRSwNP. The candidate is proposing two non-overlapping, but complementary, aims that seek to understand the role for B-cell mediated inflammation in olfactory loss in CRSwNP. In Aim 1, the candidate will utilize a set of superior turbinate tissue from CRSwNP patients and normal controls to evaluate the impact of B-cell inflammation in olfactory tissue. In Aim 2, he will establish if the autoantibodies found in CRSwNP are associated with molecular markers of pathogenicity and clinical evidence for persistent inflammation and olfactory loss following surgical therapy. During this award, Dr. Tan will also acquire practical training and coursework in immunology, biostatistics and study design. This training and the data generated though the proposed aims will form the basis for the candidate's future career as an independent investigator.

描述（由申请人提供）：Dr.布鲁斯K. Tan是西北大学Feinberg医学院耳鼻咽喉头颈外科系的助理教授，他的临床实践致力于嗅觉和嗅觉丧失。这个职业发展奖，在罗伯特P施莱默博士和杰伊A。Gottfried，专注于了解B细胞介导的炎症对慢性鼻窦炎伴鼻息肉（CRSwNP）相关的发病机制和嗅觉丧失的影响。 CRSwNP是鼻和鼻旁窦的普遍炎性病症，其是获得性嗅觉丧失的主要原因。目前，人们对导致这种疾病的炎症机制知之甚少，从而限制了用于治疗这种疾病的治疗药物的类别。我们有越来越多的证据和进一步的初步数据表明，B细胞炎症和自身免疫存在于一些鼻息肉中，并可能在与CRSwNP相关的持续炎症中发挥重要作用。 候选人提出了两个不重叠但互补的目标，旨在了解B细胞介导的炎症在CRSwNP嗅觉丧失中的作用。 在目标1中，候选人将利用来自CRSwNP患者和正常对照的一组上级鼻甲组织来评价B细胞炎症对嗅觉组织的影响。 在目标2中，他将确定CRSwNP中发现的自身抗体是否与致病性的分子标志物和手术治疗后持续炎症和嗅觉丧失的临床证据相关。在此期间，Tan博士还将获得免疫学，生物统计学和研究设计方面的实践培训和课程。这种培训和通过拟议目标产生的数据将成为候选人未来作为独立调查员的职业基础。