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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）是原发性脑癌中最常见、侵袭性最强的一种，预后极差