EAGER: A Microfluidic Device for Studying Environment-Triggered Migration of Glioblastoma Cells

胶质母细胞瘤(GBM)是最常见和最具侵袭性的成人原发脑肿瘤。众所周知，尽管进行了手术切除、放疗和/或化疗，但患者的生存时间不到16个月。人们越来越意识到，肿瘤与其微环境的相互作用，以及代谢因素，负责改变基因表达模式，使肿瘤能够适应和逃避肿瘤治疗。这一合作研究项目旨在开发新的生物光子学方法来识别GBM的全基因组表观遗传突变。这种方法不仅可以早期诊断基底膜，它还将导致机械刺激和代谢刺激的组合，从而能够恢复基底膜和其他实体肿瘤的凋亡(程序性细胞死亡)。这项建议有以下目标：1：发展纳米尺度的技术，以可视化和表征由机械代谢线索引起的染色质改变；目标2：染色质水平的表观遗传工程；以及目标3：识别和预测机械代谢条件的深度混合学习模型，以便在GBM中引入程序性细胞死亡。对转化细胞重新编程的新工具箱的开发将产生远远超出胶质母细胞瘤的影响。它将适用于几乎所有具有表观遗传驱动因素的疾病，其中包括大量癌症、神经退行性疾病、心血管疾病、肥胖和代谢综合征。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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 Chromatin Alteration 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.