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Elucidate genetic regulation of GBM differentiation

阐明 GBM 分化的遗传调控

基本信息

批准号：
10642431
负责人：
Jiangbing Zhou
金额：
$ 25.13万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10642431
关键词：
Acute Promyelocytic Leukemia Adult Bioinformatics Biology Brain Brain Neoplasms CRISPR/Cas technology Candidate Disease Gene Cell Differentiation process Collection Cytotoxic agent Databases Development Diagnosis Differentiation Therapy Disease Effectiveness Encapsulated Genes Genetic Glioblastoma Goals Hydrogels Iodides Lead Liposomes Malignant Neoplasms Malignant neoplasm of brain Molecular Target Neurons Operative Surgical Procedures Patients Predisposition Prognosis Property Public Health RNA interference screen Radiation therapy Regimen Regulation Research Research Project Grants Resistance Therapeutic Toxic effect Tretinoin Tumorigenicity United States Validation Work candidate identification chemotherapeutic agent effective therapy genome-wide improved lead candidate molecular marker nanoparticle nestin protein novel novel strategies patient derived xenograft model pharmacologic single-cell RNA sequencing stem cell differentiation stem cells success targeted delivery temozolomide therapeutic evaluation therapeutic target

项目摘要

Glioblastoma (GBM) is the most common and aggressive form of primary brain cancer with extremely poor prognosis. New approaches for improved treatment of this disease are desperately needed. Accumulating evidence suggests that the lack of effective treatment for this disease is because the existing regimens cannot effectively eliminate glioblastoma stem cells (GSCs), the root of GBM development. One promising approach to eliminating GSCs is to induce GSC differentiation. Unfortunately, the development of differentiation therapy for GBM has been limited by our poor understanding of the biology of GSC differentiation. In this application, we propose to characterize genetic regulation of GSC differentiation and validate genes that can be targeted for effective GBM differentiation therapy. As preliminary work, we identified a group of genes, which potentially regulate GSC differentiation toward specific lineages through a combination of RNAi screening and single-cell RNA sequencing approach. In this application, we will characterize lead GSC differentiation regulatory candidate genes in Aim 1, and to determine the therapeutic potential of selected genes for GSC differentiation therapy in Aim 2. Success of this project will lead to identification of novel GSC differentiation regulators that can be potentially targeted for improved treatment of GBM.

胶质母细胞瘤 (GBM) 是最常见、最具侵袭性的原发性脑癌，其预后极差。预后。迫切需要改善这种疾病治疗的新方法。积累中有证据表明，这种疾病缺乏有效的治疗方法是因为现有的治疗方案无法有效消除胶质母细胞瘤干细胞（GSC），这是GBM发展的根源。一种有前途的方法消除GSC就是诱导GSC分化。不幸的是，分化疗法的发展由于我们对 GSC 分化生物学的了解不足，GBM 的研究受到限制。在这个应用程序中，我们建议描述 GSC 分化的遗传调控特征并验证可靶向的基因进行有效的 GBM 分化治疗。作为初步工作，我们确定了一组基因，这些基因可能通过 RNAi 筛选和单细胞相结合调节 GSC 向特定谱系的分化 RNA测序方法。在此应用中，我们将描述领先的 GSC 分化监管目标 1 中的候选基因，并确定所选基因对 GSC 分化的治疗潜力目标 2 中的治疗。该项目的成功将导致新型 GSC 分化调节剂的鉴定，这些调节剂可能是改善 GBM 治疗的潜在目标。