Nasal progenitor cells and olfactory neurogenesis

鼻祖细胞和嗅觉神经发生

• 批准号: 8766365
• 负责人: Bradley J Goldstein
• 金额: $ 22.12万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-17 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8766365
• 关键词: Address; Adult; Affect; Afferent Neurons; Aging; Aging-Related Process; American; Anosmia; Appointment; Area; Basal Cell; Biometry; Biophysics; Cell Therapy; Cell physiology; Cells; Clinical Treatment; Clinical Trials; Coculture Techniques; Commit; Craniocerebral Trauma; Cre-LoxP; Data; Development; Diphtheria Toxin; Disease; Elderly; Embryo; Epithelial; Ethics; Failure; Fostering; Future; Genetic; Goals; Hares; Impairment; In Vitro; Injury; Institutes; Intake; Lamina Propria; Lead; Lesion; Life; Maintenance; Maps; Mentors; Mesenchymal; Mesenchymal Stem Cells; Monitor; Mus; National Institute on Deafness and Other Communication Disorders; Natural regeneration; Neuroepithelial; Neurons; Nose; Nutritional; Olfactory Mucosa; Otolaryngology; Patients; Peripheral Blood Stem Cell; Physicians; Physiology; Population; Positioning Attribute; Process; Property; Proto-Oncogene Protein c-kit; Quality of life; Receptor Protein-Tyrosine Kinases; Regenerative Medicine; Research; Research Design; Research Personnel; Role; Safety; Scientist; Signal Pathway; Sinusitis; Smell Perception; Stem cells; System; Taste Perception; Techniques; Testing; Tissues; Training Programs; United States; Universities; Upper Respiratory Infections; Visit; Work; base; career development; clinical practice; design; effective therapy; experience; improved; in vivo; interest; meetings; neuroepithelium; neurogenesis; neuron loss; neuronal replacement; novel; professor; progenitor; programs; public health relevance; receptor; reconstitution; repaired; research study; stem; therapeutic target

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.

描述（由候选人提供）：此应用程序的目标是提供监督培训计划，以促进候选人发展成为独立的医生 - 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。该提案将使候选人能够通过研究鼻干细胞和特定信号通路的指导计划来追求他对嗅觉系统再生机制的兴趣。研究计划：虽然鼻子中的嗅觉神经元不断地被祖细胞或干细胞取代，但某些条件可能导致嗅觉功能丧失，这很可能是修复过程失败的结果。头部受伤、既往上呼吸道感染、活动性鼻窦炎或衰老过程可能导致嗅觉丧失。目前尚无针对感音神经性嗅觉丧失的有效治疗方法。该提案的广泛、长期目标是开发治疗嗅觉丧失的新疗法。我们对确定调节嗅觉祖细胞的机制的兴趣导致了一项新发现：表达 c-kit 受体的嗅觉细胞可以产生嗅觉神经元。该提案的中心假设是 c-kit (+) 祖细胞在成人嗅觉维持中发挥关键作用。这里提出的实验将直接定义鼻 c-kit (+) 祖细胞在嗅觉中的作用 不同条件下的神经发生和再生。定义嗅觉神经元替代的特定鼻干细胞和祖细胞的功能，并确定其调节机制，是建立嗅觉丧失新疗法的重要步骤。培训计划：候选人将参加教学计划以促进其职业发展。迈阿密大学有关伦理、研究设计和生物统计学的课程和研讨会将接受审核。此外，他还将参加耳鼻喉科和干细胞研究所的智力活动。将利用与顾问的频繁会议来监控进展情况。 ISCI 主任 Josh Hare 博士和生理学和生物物理学教授 Nirupa Chaudhari 博士将担任导师。