Genetically Mediated Hair Cell Degeneration in 3D Inner Ear Organoids

3D 内耳类器官中遗传介导的毛细胞变性

基本信息

  • 批准号:
    9892994
  • 负责人:
  • 金额:
    $ 17.88万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-04-01 至 2022-03-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY This proposal describes a 5-year training program for the development of a clinician-scientist investigator in stem cell biology and large-scale genomics. The primary goal of this application is to serve as a basis for training Rick Nelson, MD, PhD in the critical skills necessary to become an independent scientific investigator studying inner ear hair cell degeneration. Dr. Nelson is currently an Assistant Professor at Indiana University School of Medicine where he will expand his scientific skills through course work, university resources and mentoring. Hearing loss and vestibular dysfunction affect millions of people worldwide and the common pathophysiologic finding is loss of the mechanosensitive hair cells. Eri Hashino, PhD will serve as Dr. Nelson's primary mentor and train him in stem cell biology. Dr. Hashino is an international leader is stem cell biology and has trained numerous postdoctoral fellows and clinician-scientists. Richard JH Smith, MD at University of Iowa will serve as Dr. Nelson's co-mentor and train him in large-scale genomic approaches and bioinformatics. Dr. Smith is an internationally renowned clinician-scientist and leader in human genetics. Dr. Nelson will also enroll in the Independent Investigator Incubator (I3) program at Indiana University, which provides guidance in scientific and career development. D. Wade Clapp, MD is an internationally recognized clinician-scientist who will serve as a career advisor for Dr. Nelson. His advisory committee will provide broad expertise that spans research planning and career development. In this proposal, the PI will establish a novel model of hair cell degeneration using mouse stem cell-derived 3D cultures containing mechanosensitive hair cells. CRISPR gene editing technology will be used to disrupt the Tmprss3 gene, which is known to cause hair cell degeneration in mice and humans. Next, the PI will use proteomic approaches to establish the protein interactome of the Tmprss3 serine protease in hair cells. Finally, single-cell RNA sequencing (RNA-seq) technology will be used to study global alterations in gene expression that lead to hair cell degeneration. The scientific environment, support from the Department of Otolaryngology at Indiana University and the internationally renowned mentors together make this project feasible. These factors maximize the potential to attain Dr. Nelson's long-term career goal of becoming an independent clinician-investigator and discovering new targets to prevent or delay hair cell degeneration.
项目摘要 该提案描述了一个为期5年的培训计划,用于培养临床科学家研究者, 干细胞生物学和大规模基因组学。此应用程序的主要目标是作为 培训里克纳尔逊,医学博士,博士的关键技能,成为一个独立的科学调查员 研究内耳毛细胞退化纳尔逊博士目前是印第安纳州大学的助理教授 医学院,他将通过课程工作,大学资源和 指导。听力损失和前庭功能障碍影响着全世界数百万人, 病理生理学发现是机械敏感毛细胞的损失。桥野绘里博士将担任纳尔逊博士的 主要指导并训练他干细胞生物学。桥野博士是干细胞生物学的国际领导者 并培养了许多博士后研究员和临床科学家。理查德JH史密斯,医学博士在大学 爱荷华州将担任纳尔逊博士的共同导师,并在大规模基因组方法和生物信息学方面对他进行培训。 博士史密斯是国际知名的临床科学家和人类遗传学的领导者。纳尔逊博士也将 参加印第安纳州大学的独立研究者孵化器(I3)项目,该项目提供以下方面的指导: 科学和职业发展。D.韦德克拉普,医学博士是一个国际公认的临床科学家谁 将担任纳尔逊医生的职业顾问他的咨询委员会将提供广泛的专业知识, 研究规划和职业发展。在这项提案中,PI将建立一种新的毛细胞模型, 使用含有机械敏感毛细胞的小鼠干细胞衍生的3D培养物进行变性。CRISPR 基因编辑技术将用于破坏Tmprss 3基因,该基因已知会导致毛细胞 在小鼠和人类中的退化。接下来,PI将使用蛋白质组学方法来建立蛋白质 毛细胞中Tmprss 3丝氨酸蛋白酶的相互作用组。最后,单细胞RNA测序(RNA-seq) 这项技术将用于研究导致毛细胞退化的基因表达的整体变化。的 科学环境,来自印第安纳州大学耳鼻喉科和 国际知名导师的共同努力使这个项目切实可行。这些因素最大限度地发挥潜力, 达到博士纳尔逊的长期职业目标,成为一名独立的临床研究者,并发现 预防或延缓毛细胞退化的新靶点。

项目成果

期刊论文数量(0)
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Rick F Nelson其他文献

Speech Recognition Outcomes in Adults With Slim Straight and Slim Modiolar Cochlear Implant Electrode Arrays
使用细长直型和细长蜗轴人工耳蜗植入电极阵列的成人语音识别结果
  • DOI:
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Margaret E. MacPhail;Nathan T. Connell;D. Totten;Mitchell T. Gray;D. Pisoni;Charles W. Yates;Rick F Nelson
  • 通讯作者:
    Rick F Nelson
Cerebrospinal Fluid Leaks From the Lateral Ventricle: A Case Series
侧脑室脑脊液漏:系列病例
  • DOI:
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    2.1
  • 作者:
    Mohamad Z. Saltagi;Amy L Fraser;Mohamedkazim M Alwani;K. Mosier;Rick F Nelson
  • 通讯作者:
    Rick F Nelson
Facial Nerve Preservation With Inferior Long-Axis Dissection of Large Vestibular Schwannomas
大型前庭神经鞘瘤下长轴解剖保留面神经
  • DOI:
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    2.1
  • 作者:
    D. Totten;Nathan T. Connell;Lauren A Howser;Elaine Colomb;M. Sandelski;Cyrus C. Rabbani;J. Savage;M. Shah;Rick F Nelson
  • 通讯作者:
    Rick F Nelson
Rationale for the Development of a Novel Clinical Grading Scale for Postoperative Facial Nerve Function: Results of a Multidisciplinary International Working Group
开发新型术后面神经功能临床分级量表的基本原理:多学科国际工作组的结果
  • DOI:
    10.1097/mao.0000000000004039
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    2.1
  • 作者:
    Matthew L. Carlson;Christine Lohse;S. Agazzi;Seilesh C. Babu;Frederick G Barker;Samuel Barnett;W. L. Bi;Nigel Biggs;K. Boahene;Joseph T Breen;Kevin D. Brown;Per Cayé;Maura K. Cosetti;N. Deep;Jacob K. Dey;James R. Dornhoffer;D. Forner;R. Gurgel;Marlan R. Hansen;Jacob B. Hunter;Michel Kalamarides;Irene A Kim;Andrew T King;M. Kircher;Luis Lassaletta;Michael J. Link;S. Lloyd;M. Lund;John P. Marinelli;Cordula Matthies;Vikas Mehta;Eric J. Moore;A. Nassiri;B. Neff;Rick F Nelson;Jeffrey J. Olson;Neil S Patel;M. Celda;Aaron R. Plitt;Daniel L. Price;J. Thomas Roland;A. Sweeney;Kendall K. Tasche;Marcos Tatagiba;Ø. Tveiten;Jamie J. Van Gompel;Jeffrey T. Vrabec;G. Wanna;Peter A. Weisskopf
  • 通讯作者:
    Peter A. Weisskopf
Trends in Spontaneous Cerebrospinal Fluid Leak Repairs in the United States, 2009–2018
2009-2018 年美国自发性脑脊液漏修复趋势
  • DOI:
    10.1097/ono.0000000000000021
  • 发表时间:
    2022
  • 期刊:
  • 影响因子:
    0
  • 作者:
    D. Totten;Elizabeth A Schueth;Mohamad Z. Saltagi;Cyrus C. Rabbani;A. Harris;Dani Tressman;S. Hohmann;Rick F Nelson
  • 通讯作者:
    Rick F Nelson

Rick F Nelson的其他文献

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{{ truncateString('Rick F Nelson', 18)}}的其他基金

Mechanisms of Mammalian Genetic Hearing Loss
哺乳动物遗传性听力损失的机制
  • 批准号:
    10660134
  • 财政年份:
    2023
  • 资助金额:
    $ 17.88万
  • 项目类别:
Genetically Mediated Hair Cell Degeneration in 3D Inner Ear Organoids
3D 内耳类器官中遗传介导的毛细胞变性
  • 批准号:
    9293747
  • 财政年份:
    2017
  • 资助金额:
    $ 17.88万
  • 项目类别:
Genetically Mediated Hair Cell Degeneration in 3D Inner Ear Organoids
3D 内耳类器官中遗传介导的毛细胞变性
  • 批准号:
    10132291
  • 财政年份:
    2017
  • 资助金额:
    $ 17.88万
  • 项目类别:

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