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

简介(申请人提供)：布鲁斯·K·谭博士是西北大学范伯格医学院耳鼻喉科-头颈外科的助理教授，他的临床实践致力于鼻腔和嗅觉丧失。该职业发展奖由Robert P.Schlemer博士和Jay A.Gottfred博士指导，旨在了解B细胞介导的炎症对慢性鼻窦炎鼻息肉(CRSwNP)的发病机制和嗅觉丧失的影响。CRSwNP是鼻腔和副鼻窦炎性疾病，是后天性嗅觉丧失的主要原因。目前，导致这种疾病的炎症机制还不清楚，因此限制了用于治疗这种疾病的治疗药物的种类。我们有越来越多的证据和进一步的初步数据表明，一些鼻息肉中存在B细胞炎症和自身免疫，并可能在CRSwNP相关的持续性炎症中发挥重要作用。这位候选人提出了两个不重叠但互补的目标，试图了解B细胞介导的炎症在CRSwNP嗅觉丧失中的作用。在目标1中，候选人将利用一组来自CRSwNP患者和正常对照组的上鼻甲组织来评估B细胞炎症对嗅觉组织的影响。在目标2中，他将确定在CRSwNP中发现的自身抗体是否与致病性的分子标记以及手术治疗后持续炎症和嗅觉丧失的临床证据有关。在这个奖项期间，陈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。这一培训和通过拟议目标产生的数据将构成候选人作为独立调查员的未来职业生涯的基础。

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.