Functional Genomics of High Grade Glioma

高级别胶质瘤的功能基因组学

基本信息

批准号：
10044632
负责人：
KWANHA YU
金额：
$ 15.23万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-02 至 2025-08-31
项目状态：
未结题

项目摘要

Glioma is the most common and deadly disease affecting the CNS. Current projections suggest 22,000 new cases annually, of which 13,000 will be Glioblastoma Multiforme, which is universally fatal. Despite over 60 years of research, there have been no significant improvements to patient outcome. More recently, high throughput molecular sequencing technology has open the field of genomics and big data, in the hopes of providing novel insight to the disease and potential therapeutic inroads. However, these efforts have largely served to refine diagnosis rather than improve patient prognosis. In an effort to translate the wealth of patient genomics information beyond identifying novel informatics trends, our program seeks to biologically functionalize genomics information. More specifically, we have developed tools and approaches that overcome the pragmatic hurdles of traditional methods. We have taken our previously developed in utero electroporation- glioma model and added barcode targeting next generation sequencing, resulting in a fully in vivo, non-viral screening system to test at least 50 different genetic factors. In advancing forward, we seek to: 1) further pursue our previous findings to understand the molecular mechanisms driving the phenomenon we’ve observed, 2) advance and upgrade our methods to meet the needs of other systems, and 3) apply our approach to investigate glioma-associated epilepsy, an associated co-morbidity. Our larger initiative in functional genomics will: 1) provide new tools and methods for screening and testing genetic anomalies found in glioma, 2) provide molecular insight into the mechanism that differentially promote variant specific gliomagenesis within an allelic series, 3) begin to demonstrate the unique biology of familial glioma, and 4) further investigate the mechanisms underlying glioma driven hyperexcitably thereby addressing a much under investigated quality of life concern. Ultimately, our programs exists to gain greater insight into the molecular mechanisms that drive gliomagenesis and associated co-morbidities. This will provide understanding towards novel therapeutic vulnerabilities.

神经胶质瘤是影响中枢神经系统的最常见、最致命的疾病，目前预测新增 22,000 例。每年有 13,000 例多形性胶质母细胞瘤病例，尽管有 60 多例，但普遍致命。经过多年的研究，患者的治疗效果并没有显着改善，但最近，高。高通量分子测序技术开启了基因组学和大数据领域，希望提供了对该疾病的新见解和潜在的治疗进展然而，这些努力在很大程度上取得了进展。旨在完善诊断而不是改善患者预后，以努力转化患者的财富。基因组学信息除了识别新的信息学趋势之外，我们的计划还寻求从生物学角度更具体地说，我们开发了能够克服这些问题的工具和方法。我们采用了之前开发的子宫内电穿孔技术，克服了传统方法的实用障碍。神经胶质瘤模型并添加了针对下一代测序的条形码，从而产生了完全体内的非病毒测试至少 50 种不同遗传因素的筛查系统在前进过程中，我们寻求： 1) 进一步。追寻我们之前的发现，以了解驱动我们所发现的现象的分子机制观察到，2）改进和升级我们的方法以满足其他系统的需求，3）应用我们的方法方法来研究神经胶质瘤相关的癫痫，这是我们的一项更大的举措。功能基因组学将：1）为筛选和测试发现的遗传异常提供新的工具和方法在神经胶质瘤中，2) 提供对差异性促进变异特异性的机制的分子洞察等位基因系列中的神经胶质瘤发生，3) 开始展示家族性神经胶质瘤的独特生物学，以及 4) 进一步研究神经胶质瘤过度兴奋驱动的机制，从而解决一个远远不足的问题最终，我们的项目旨在更好地了解分子。驱动神经胶质瘤发生和相关并发症的机制这将为我们提供了解。新的治疗漏洞。