Mapping Brainstem Motor Neuron Subtypes and Genetic Pathways Involved in their Differential Susceptibility to Disease
绘制脑干运动神经元亚型及其对疾病的不同易感性所涉及的遗传途径
基本信息
- 批准号:10706942
- 负责人:
- 金额:$ 23.98万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-23 至 2023-11-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
PROJECT SUMMARY/ABSTRACT
This NIH K08 proposal describes an initial five-year training program with one year extension for career
development in academic neuropathology and developmental neurogenetics. Dr. Matthew Rose has completed
clinical residency in Anatomic Pathology and fellowship in Neuropathology at Brigham and Women’s Hospital
(BWH) and Boston Children’s Hospital (BCH) at Harvard Medical School (HMS) and will embark on a research
program designed to train for an independent academic career in neurologic disease-oriented research.
In this training program, Dr. Rose will acquire in-depth experience in the study of ocular motor neuron (OMN)
development and axon targeting, interpretation of single cell RNA-sequencing, analysis of gene regulatory
networks, tissue clearing and advanced imaging approaches, and gene-editing technologies. His initial mentor
at BCH, Dr. Elizabeth Engle (a Professor of Neurology and HHMI Investigator at BCH), is a leader in brainstem
OMN development and congenital cranial dysinnervation disorders (CCDDs) that involve these motor neurons.
With Dr. Rose’s move to the University of California, Irvine (UCI), Albert La Spada, MD, PhD at UCI will
become Dr. Rose’s mentor, and Dr. Engle will continue as his co-mentor.
Both have established track records for mentoring trainees to successful careers in biomedical investigation.
In addition to his mentor, he has assembled a group of collaborators with complementary expertise in these
disciplines, and an Advisory Committee of senior faculty at UCI with extensive experience in guiding physician-
scientists through the transition to independence.
The primary scientific goal of the proposed research plan is to study normal and abnormal OMN specification
and axonal growth and guidance in health and disease. Dr. Rose provides an initial map of the genetic
differences among brainstem motor neurons that may serve as a foundation for further studies of all motor neuron
diseases. These preliminary data will be used as a foundation to further study the development of the OMN
subnuclei by discovering markers of each OMN subpopulation, and then applying those markers to the study of
the CCDDs. The central hypothesis of this proposal is that the differences in gene expression among OMN
subpopulations may predispose certain subtypes to undergo dysinnervation in different CCDDs.
Single cell RNA-seq will be performed on the three primary OMNs: the oculomotor, trochlear, and abducens
brainstem nuclei to discover markers of each subpopulation. In combination with ATAC-seq, the transcriptional
regulatory networks for OMN specification will be investigated. Unique markers of each OMN subpopulation will
then be used to study normal OMN axon projections to distinct muscle targets, as well as using them to dissect
the contributions of different populations to the stereotypic and pathologic aberrant innervations observed in the
CCDDs. These studies have significance to the broader fields of neuronal specification and differentiation and
to axonal growth and guidance.
项目总结/文摘
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Matthew F Rose其他文献
Immunohistochemical investigations of adult intraocular medulloepitheliomas
成人眼内髓上皮瘤的免疫组织化学研究
- DOI:
- 发表时间:
2015 - 期刊:
- 影响因子:4
- 作者:
F. Jakobiec;Matthew F Rose;D. Trief;A. Stagner;Ivana K. Kim;E. Gragoudas - 通讯作者:
E. Gragoudas
Matthew F Rose的其他文献
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{{ truncateString('Matthew F Rose', 18)}}的其他基金
Mapping Brainstem Motor Neuron Subtypes and Genetic Pathways Involved in their Differential Susceptibility to Disease
绘制脑干运动神经元亚型及其对疾病的不同易感性所涉及的遗传途径
- 批准号:
10416623 - 财政年份:2016
- 资助金额:
$ 23.98万 - 项目类别:
Mapping Brainstem Motor Neuron Subtypes and Genetic Pathways Involved in their Differential Susceptibility to Disease
绘制脑干运动神经元亚型及其对疾病的不同易感性所涉及的遗传途径
- 批准号:
10064032 - 财政年份:2016
- 资助金额:
$ 23.98万 - 项目类别:
Role of Math1 in brain stem & cerebellar development
Math1 在脑干中的作用
- 批准号:
6963377 - 财政年份:2004
- 资助金额:
$ 23.98万 - 项目类别:
Role of Math1 in brain stem & cerebellar development
Math1 在脑干中的作用
- 批准号:
7107867 - 财政年份:2004
- 资助金额:
$ 23.98万 - 项目类别:
Role of Math1 in brain stem & cerebellar development
Math1 在脑干中的作用
- 批准号:
6887091 - 财政年份:2004
- 资助金额:
$ 23.98万 - 项目类别:
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