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

简介（由申请人提供）：Bruce K. Tan博士是西北大学范伯格医学院耳鼻喉头颈外科的助理教授，他的临床实践致力于鼻科学和嗅觉丧失。这个职业发展奖项，在dr。Robert P. Schleimer和Jay A. Gottfried的研究重点是了解b细胞介导的炎症对慢性鼻窦炎伴鼻息肉（CRSwNP）的发病机制和嗅觉丧失的影响。CRSwNP是鼻子和副鼻窦的一种常见炎症，是获得性嗅觉丧失的主要原因。目前，驱动这种疾病的炎症机制尚不清楚，因此限制了用于治疗这种疾病的治疗剂的种类。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。该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Aim 1中，候选人将利用一组来自CRSwNP患者和正常对照的上鼻甲组织来评估嗅觉组织中b细胞炎症的影响。在Aim 2中，他将确定在CRSwNP中发现的自身抗体是否与手术治疗后持续炎症和嗅觉丧失的致病性分子标记和临床证据相关。在此期间，谭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。这种培训和通过提出的目标产生的数据将构成候选人未来作为独立调查员职业生涯的基础。

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.