EFRI CEE: Opening the Gates of Apoptosis in Cancer

EFRI CEE：打开癌症细胞凋亡之门

基本信息

批准号：
2129617
负责人：
Stefan Bossmann
金额：
$ 200万
依托单位：
University of Kansas Medical Center Research Institute Inc
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2024-12-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2129617&HistoricalAwards=false
关键词：
EFRI CEE Opening Gates Apoptosis

项目摘要

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.

胶质母细胞瘤（GBM）是最常见，最具侵略性的成年原发性脑肿瘤。尽管手术切除，放射线和/或化学疗法，GBM以患者的生存率不足16个月而闻名。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子以及代谢因素负责改变基因表达模式，这使肿瘤能够适应和逃避肿瘤治疗。该协作研究项目旨在开发新型的生物体方法，以识别GBM基因组范围的表观遗传突变。该方法不仅将允许早期诊断GBM，还将导致机械和代谢刺激的结合，这将能够恢复GBM和其他实体瘤中的凋亡（=程序性细胞死亡）。该提案具有以下目的：1：开发纳米级技术，用于可视化和通过机械代谢提示引起的色谱物的特征； AIM 2：染色质水平表观遗传学工程；和目标3：一种深层的混合学习模型，以识别和预测GB中引入程序性细胞死亡的机械代谢条件。开发用于重新编程转化细胞的新工具箱的开发将其含义远远超出胶质母细胞瘤。它将适用于几乎所有具有表观遗传驱动因素的疾病，其中包括许多癌症，神经退行性疾病，心血管疾病，肥胖和代谢综合征。这项奖项反映了NSF的法定任务，并被认为是通过基金会的知识分子优点和广泛的影响来审查CRERIA的评估。

项目成果

期刊论文数量（22）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Characterization of a Novel Thermostable DNA Lyase Used To Prepare DNA for Next-Generation Sequencing.

DOI：
10.1021/acs.chemrestox.2c00172
发表时间：
2023-02-20
期刊：
CHEMICAL RESEARCH IN TOXICOLOGY
影响因子：
4.1
作者：
Baljinnyam, Tuvshintugs;Conrad, James W.;Sowers, Mark L.;Chang-Gu, Bruce;Herring, Jason L.;Hackfeld, Linda C.;Zhang, Kangling;Sowers, Lawrence C.
通讯作者：
Sowers, Lawrence C.

A combinatorial system to examine the enzymatic repair of multiply damaged DNA substrates.

DOI：
10.1093/nar/gkac530
发表时间：
2022-07-22
期刊：
NUCLEIC ACIDS RESEARCH
影响因子：
14.9
作者：
Hsu, Chia Wei;Conrad, James W.;Sowers, Mark L.;Baljinnyam, Tuvshintugs;Herring, Jason L.;Hackfeld, Linda C.;Hatch, Sandra S.;Sowers, Lawrence C.
通讯作者：
Sowers, Lawrence C.

Chemical and enzymatic modifications of 5-methylcytosine at the intersection of DNA damage, repair, and epigenetic reprogramming.