EFRI CEE: Opening the Gates of Apoptosis in Cancer

胶质母细胞瘤（GBM）是最常见和最具侵袭性的成人原发性脑肿瘤。GBM是已知的病人？尽管进行了手术切除、放疗和/或化疗，患者的生存期仍低于16个月。随着人们越来越认识到肿瘤与其微环境的相互作用，以及代谢因素，是改变基因表达模式的原因，这使得肿瘤能够适应和逃避肿瘤治疗。这项合作研究项目旨在开发新的生物光子方法来识别GBM中的全基因组表观遗传突变。这种方法不仅允许GBM的早期诊断，还将导致机械和代谢刺激的组合，这将能够恢复GBM和其他实体瘤中的细胞凋亡（=程序性细胞死亡）。该提案具有以下目标：1：开发用于机械代谢线索诱导的染色质改变的可视化和表征的纳米级技术;目标2：染色质水平表观遗传工程;以及目标3：一种识别和预测机械故障的深度混合学习模型在GBM中引入程序性细胞死亡的代谢条件。开发一个新的工具箱用于转化细胞的重编程将具有以下意义：远不止胶质母细胞瘤该奖项将适用于几乎所有具有表观遗传驱动因素的疾病，其中包括许多癌症、神经退行性疾病、心血管疾病、肥胖症和代谢综合征。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Glioblastoma (GBM) is the most common and most aggressive adult primary brain tumor. GBM is known for the patient?s poor survival of less than 16 months despite surgical resection, radiation, and/or chemotherapy. There is a growing awareness that the interaction of tumors with their microenvironment, together with metabolic factors, is responsible for altering gene expression patterns, which enable the tumor to adapt and escape tumor treatment.This collaborative research project aims to develop novel biophotonic methods to recognize genome-wide epigenetic mutations in GBM. This methodology will not only permit the early diagnosis of GBM, it will also lead to a combination of mechanic and metabolic stimuli, which will be able to restore apoptosis (= programmed cell death) in GBM and other solid tumors. This proposal has the following aims:1: Development of Nanoscale Technologies for Visualization and Characterization of ChromatinAlteration Induced by Mechano-metabolic Cues; Aim 2: Chromatin Level Epigenetic Engineering; and Aim 3: A Deep Hybrid Learning Model to Recognize and Predict Mechano-metabolic Conditions for Introducing Programmed Cell Death in GBM.The development of a new toolbox for reprogramming of transformed cells will have implications that will reach far beyond glioblastoma. It will apply to virtually all diseases with epigenetic drivers, among them numerous cancers, neurodegenerative diseases, cardiovascular diseases, obesity and metabolic syndrome.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.