The Sox9/NFIA Transcriptional Network In Malignant Glioma

恶性胶质瘤中的 Sox9/NFIA 转录网络

• 批准号: 9307752
• 负责人: Stacey Marie Glasgow
• 金额: $ 14.04万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-06 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9307752
• 关键词: Address; Adult; Area; Award; Biology; Brain Neoplasms; Cancer Biology; Cell Lineage; Cell Therapy; Cellular biology; ChIP-seq; Collaborations; Complex; Core Facility; Development; Developmental Biology; Differentiation Therapy; Disease; Doctor of Philosophy; Electroporation; Environment; Equipment; Faculty; Fellowship; Flow Cytometry; Funding; Gene Expression Profiling; Generations; Genes; Genetic Epistasis; Genetic Transcription; Glioma; Gliomagenesis; Goals; Grant; Histologic; Human; Human Cell Line; Immunotherapy; Institution; Journals; Laboratories; Lead; Learning; Malignant Glioma; Malignant Neoplasms; Malignant neoplasm of brain; Mediating; Medical center; Medicine; Mentored Research Scientist Development Award; Mentors; Modeling; Multiple Sclerosis; Mus; Nature; Neuroglia; Neurosciences; Nuclear; Oligodendroglia; Oncogenes; Oncogenic; Paper; Pathogenesis; Pathologic; Play; Positioning Attribute; Postdoctoral Fellow; Process; Progression-Free Survivals; Publishing; Recording of previous events; Regenerative Medicine; Research; Research Technics; Role; Specific qualifier value; Spinal Cord; Stem cells; Survival Rate; System; Techniques; Technology; Testing; Texas; Therapeutic; Time; Training; Transcriptional Regulation; Translating; Translational Research; Underrepresented Minority; United States National Institutes of Health; Universities; Work; axon guidance; base; cancer genome; career; career development; cohort; college; combat; experimental study; gain of function; gene function; gene therapy; genomic RNA; glial cell development; gliogenesis; glioma cell line; human disease; in utero; in vitro Assay; in vivo; innovation; insight; interest; loss of function; member; mouse model; nerve stem cell; new therapeutic target; novel; oligodendroglioma; outcome forecast; programs; public health relevance; skills; stem cell biology; symposium; transcription factor; tumor; tumorigenesis

 DESCRIPTION (provided by applicant): Candidate Upon graduating with a Ph.D. from the integrative biology department of the University of Texas Southwestern Medical Center, I pursued a post-doctoral position in the lab or Dr. Soo-Kyoung Lee at Baylor College of Medicine (Houston, TX), during which I studied the transcriptional programs that orchestrate the expression of axon guidance factors in the developing spinal cord. My work in the Lee lab was supported by the supplemental grant for underrepresented minorities from the NIH. To move my career trajectory toward a more translational area of study, I undertook a second post-doctoral position in the laboratory of Dr. Deneen at Baylor College of Medicine, where I have worked for three years. I am now applying for more senior fellowships/awards and beginning to take the initial steps toward establishing my own research program. My current work is driven by an interest in combining my skills and expertise in developmental biology with disease-based models of tumorigenesis. Obtaining the NCI Mentored Research Scientist Development Award (K01) will allow me to gain both the additional conceptual/ technical training and pursue the career development activities I have outlined in this application such as, journal clubs, seminars, and conferences. With this additional training I will be able to pursue an independent research position at a highly ranked institution. My overall career goal is to initiate and sustain a successful research career in glial lineage development and transcriptional regulation of gliomagenesis. My goals for the mentored career award include publishing three first-author papers in high-impact journals; learn concepts and research techniques in the area of cancer biology; and to complete the career development activities that will launch my independent research program and funding. I hope to make a significant contribution to the understanding of glial cell biology and glioma tumorigenesis with the ultimate goal of translational application. Environment Baylor College of Medicine (BCM) is a premier research institution with a strong commitment to research and finding new treatments and cures for disease. As a part of the Cell and Gene Therapy (CAGT), and Stem Cells and Regenerative Medicine Center (STaR), I will have access to a large array of equipment and a wide range of core facilities with expertise in Flow Cytometry and genomic/RNA profiling. The CAGT and STaR centers have a long history of translational research; faculty have a diverse range of interests including immunotherapy and stem cell biology. The centers encourage interaction and collaboration among its members which provides a rich environment for my additional scientific training. The CAGT is particularly well suited for studying gliomagenesis as several faculty members with specific expertise in glioma biology and immunotherapy approaches to brain tumors have committed to supporting my proposed project. Research During my time in the Deneen lab I have studied the transcriptional regulation of developmental gliogenesis and have begun to translate these developmental concepts to the study of glioma. I have identified a transcriptional cascade consisting of two transcription factors, Sox9 and NFIA, which orchestrate the initiation of gliogenesis in the developing spinal cord. Furthermore, I have found transcriptional functions for NFIA in oligodendrocytes and multiple sclerosis. Currently, I am examining the Sox9/NFIA relationship in more detail and hypothesize that the developmental relationship between Sox9 and NFIA is maintained during gliomagenesis. The experiments proposed here are geared toward examining this relationship in malignant glioma. I utilize a highly innovative and novel mouse model of glioma which rapidly generates (within 3 weeks) malignant gliomas, combined with complementary studies in primary human glioma cell lines to study the roles of NFIA and Sox9 in glioma tumorigenesis. The importance of transcriptional regulation of developmental determining factors in glioma tumorigenesis is just beginning to be explored. My proposed transcriptional profiling experiments in malignant gliomas using a combination of ChIP-seq and gene expression profiling technologies will serve as a platform for studying the relationship between developmental programs and gliomagenesis. I believe that the research outlined in this project can contribute to the fundamental understanding of gliogenesis and glioma tumorigenesis and will have relevance to human gliomas.

 描述（由适用提供）：毕业后候选人博士学位。在德克萨斯大学西南医学中心的综合生物学系中，我在实验室中担任博士后职位，或者在德克萨斯州贝勒医学院（休斯顿）的Soo-kyoung Lee博士中，在此期间，我研究了转录计划，这些程序在发育中发育中的脊柱中辅助轴突引导因素的表达。我在Lee Lab的工作得到了NIH的补充赠款的支持。为了将自己的职业发展轨迹转移到一个更翻译的研究领域，我在贝勒医学院Deneen博士的实验室中担任了第二个博士后职位，在那里我工作了三年。我现在正在申请更多的高级奖学金/奖项，并开始采取最初的步骤来建立自己的研究计划。我目前的工作是由将我的技能和专家与基于疾病的肿瘤发生模型相结合的兴趣所驱动的。获得NCI指导的研究科学家发展奖（K01）将使我能够获得额外的概念/技术培训，并购买我在此应用程序中概述的职业发展活动，例如期刊俱乐部，semiars， 和会议。通过这项额外的培训，我将能够在高级机构担任独立的研究职位。我的整体职业目标是发起和维持神经胶质谱系的成功研究生涯，对神经胶质作用的转录调节。我的修订职业生涯奖的目标包括在高影响力期刊上发表三篇第一章论文；在癌症生物学领域学习概​​念和研究技术；并完成将启动我独立研究计划和资金的职业发展活动。我希望对理解神经胶质细胞生物学和神经胶质瘤肿瘤发生做出重大贡献，以翻译应用的最终目的。环境贝勒医学院（BCM）是一家主要的研究机构，致力于研究和寻找新的疾病治疗方法。作为细胞和基因疗法（CAGT）以及干细胞和再生医学中心（Star）的一部分，我将可以使用各种设备和广泛的核心设施，具有流式细胞仪和基因组/RNA分析方面的专业知识。 CAGT和明星中心具有悠久的转化研究历史。教师具有潜水员的兴趣范围，包括免疫疗法和干细胞生物学。这些中心鼓励其成员之间的互动和协作，这为我的其他科学培训提供了丰富的环境。 CAGT特别适合研究神经胶质作用，因为几位在神经胶质瘤生物学方面具有特定专业知识的教职员工和脑肿瘤的免疫疗法方法已致力于支持我所提出的项目。在Deneen实验室期间，我研究了发育神经胶质发生的转录调控，并开始将这些发育概念转化为神经胶质瘤的研究。我已经确定了由两个转录因子Sox9和NFIA组成的转录级联，该因子策划了发育中的脊髓中神经胶质发生的开始。此外，我发现了少突胶质细胞和多发性硬化症中NFIA的转录功能。目前，我正在更详细地检查SOX9/NFIA关系，并假设在神经胶质性过程中保持SOX9和NFIA之间的发育关系。此处提出的实验旨在检查恶性神经胶质瘤中的这种关系。我利用了一种高度创新性和新颖的胶质瘤小鼠模型，该模型迅速产生（3周之内）恶性神经胶质瘤，并在原代人神经胶质瘤细胞系中进行完整的研究来研究NFIA和SOX9在神经胶质瘤肿瘤发生中的作用。刚刚开始探索神经胶质瘤肿瘤发生中发展因子的转录调节的重要性。我提出的在恶性神经胶质瘤中使用芯片序列和基因表达谱技术的结合将作为研究发育程序与胶质作用之间关系的平台。我认为，该项目中概述的研究可以有助于对神经胶质性和神经胶质瘤肿瘤发生的基本理解，并将与人神经胶质瘤相关。