Nasal progenitor cells and olfactory neurogenesis

描述（由候选人提供）：本申请的目标是提供一个有监督的培训计划，以促进候选人发展成为一名独立的医生-科学家。这将通过迈阿密大学耳鼻喉科和跨学科干细胞研究所（ISCI）的协调努力来完成。该建议将使候选人能够通过指导计划研究鼻干细胞和特定信号通路来追求他对嗅觉系统再生机制的兴趣。研究项目：虽然鼻子里的嗅觉神经元不断被祖细胞或干细胞取代，但某些情况下可能导致嗅觉功能丧失，这可能是修复过程失败的结果。嗅觉丧失可发生在头部损伤、先前上呼吸道感染、活动性鼻窦炎或衰老过程的结果之后。目前对于感觉神经性嗅觉缺失还没有有效的治疗方法。这项提议的长远目标是开发新的治疗嗅觉缺失的方法。我们对确定调节嗅觉祖细胞的机制的兴趣导致了新的发现，即表达c-kit受体的嗅觉细胞可以产生嗅觉神经元。该建议的中心假设是c-kit（+）祖细胞在成人嗅觉维持中起关键作用。本文提出的实验将直接确定鼻腔c-kit（+）祖细胞在嗅觉中的作用

DESCRIPTION (provided by candidate): The goal of this application is to provide a supervised training program that will promote the candidate's development into an independent physician - scientist. This will be accomplished through a coordinated effort in the Department of Otolaryngology and the Interdisciplinary Stem Cell Institute (ISCI), at University of Miami. This proposal will enable the candidate to pursue his interest in mechanisms of regeneration in the olfactory system through a mentored plan to study nasal stem cells and specific signaling pathways. Research Program: Although olfactory neurons in the nose are replaced continually from progenitor or stem cells, certain conditions can lead to a loss of olfactory function that likly is a consequence of failures in this repair process. Anosmia can occur following head injury, prior upper respiratory infections, active sinusitis, or as a consequence of the aging process. There are currently no effective treatments for sensorineural anosmia. The broad, long term goals of this proposal are to develop novel treatments for anosmia. Our interest in determining mechanisms regulating olfactory progenitors has led to the novel finding that olfactory cells expressing the c-kit receptor can give rise to olfactory neurons. The central hypothesis of this proposal is that c-kit (+) progenitor cells serve a key role in adult olfactory maintenance. The experiments proposed here will directly define the role of nasal c-kit (+) progenitors in olfactory neurogenesis and regeneration under various conditions. Defining the function of specific nasal stem and progenitor cells underlying olfactory neuronal replacement, and determining their regulatory mechanisms, are essential steps towards the establishment of new treatments for anosmia. Training Program: The candidate will participate in a didactic program to enhance his career development. Courses and seminars at University of Miami relating to ethics, research design, and biostatistics will be audited. Also, he will participate in intellectual activities in he Otolaryngology Department and the Stem Cell Institute. Frequent meetings with advisors will be utilized to monitor progress. Dr. Josh Hare, ISCI Director, and Dr. Nirupa Chaudhari, Professor of Physiology and Biophysics, will serve as Mentors.