Genome Stability Program

翻译后摘要：基因组稳定性（GS） 基因组稳定性（GS）计划致力于了解维持 基因组完整性，这些过程如何在癌细胞中改变，以及最终这些改变如何在癌细胞中发生。 用来杀死肿瘤细胞该计划有四大主题：（1）基因组稳定性机制，（2） 辐射和氧化损伤，（3）遗传毒性应激反应，以及（4）衰老和癌症。基本 基因组稳定性的研究对于促进对肿瘤形成机制的理解至关重要 并为癌症诊断、治疗和预防提供了新靶点和策略的有价值来源。 该计划的重要亮点是关于DNA修复作用的开创性发现 蛋白质在单分子水平上，使用靶向的端粒氧化碱基损伤来研究 随后的端粒功能障碍，端粒（ALT）途径的替代性延长的作用， 侵袭性神经母细胞瘤，减轻辐射损伤方法的发展，机制 深入了解细胞死亡途径，包括铁凋亡，以及ATR抑制剂与电离 放射或顺铂通过增强免疫反应杀死肿瘤细胞。增长和影响 通过从匹兹堡大学招聘18名新教师， 通过HCC支持的招聘。该计划由Patricia Opresko博士和班尼特货车共同指导 Houten博士Opresko博士是环境和职业健康教授， 因其对端粒生物学的分子见解的工作而受到认可，并为基因组提供了重要的联系。 稳定性计划（GS）和集水区科学家。货车豪顿博士是理查德·M。Cyert教授 药理学和化学生物学系的分子肿瘤学，是世界上 DNA修复的分子机制和线粒体生物学。他们的研究兴趣是互补的 并提供强大的协同作用。自2015年以来，在基因组稳定性领域工作的教师人数， 癌症已经从20个成员增加到38个，来自14个部门和3个学校的大学内， 匹兹堡和13个独立的教师实验室的核心小组设在HCC大楼。GS 成员进行以癌症为重点的研究，每年直接资助总额为650万美元，其中280万美元 是NCI资金，340万美元是其他同行评审，30万美元是非同行评审。从2015年至2019年8月，GS 成员出版了516份与癌症有关的出版物，其中20%是方案内出版，40%是方案间出版， 69%的机构间合作。

Abstract: Genome Stability (GS) The Genome Stability (GS) Program is devoted to understanding the molecular pathways that maintain genome integrity, how these processes are altered in cancer cells, and finally how these alterations may be exploited to kill tumor cells. This program has four broad themes: (1) mechanisms of genome stability, (2) radiation and oxidative damage, (3) genotoxic stress responses, and (4) aging and cancer. Fundamental research in genome stability is essential for advancing understanding of the mechanisms of tumor formation and provides a valuable source of novel targets and strategies for cancer diagnosis, treatment, and prevention. Significant highlights of the program have been seminal discoveries regarding the action of DNA repair proteins at the single molecule level, the use of targeted oxidative base damage at telomeres to study subsequent telomere dysfunction, the role of the alternative lengthening of telomere (ALT) pathway in aggressive neuroblastoma tumors, development of approaches to mitigate radiation damage, mechanistic insights into cell death pathways including ferroptosis, and the use of ATR inhibitors in conjunction with ionizing radiation or cisplatin to kill tumor cells through enhanced immune responses. Growth and impact of the program has been greatly enhanced by recruiting 18 new faculty from across the University of Pittsburgh and through HCC-supported recruitment. This Program is co-directed by Patricia Opresko, PhD and Bennett Van Houten, PhD. Dr. Opresko is a Professor of Environmental and Occupational Health who is internationally recognized for her work on molecular insights into telomere biology and provides important links to Genome Stability Program (GS) and catchment area scientists. Dr. Van Houten is the Richard M. Cyert Professor of Molecular Oncology in the Department of Pharmacology and Chemical Biology and is a world expert on molecular mechanisms of DNA repair and mitochondrial biology. Their research interests are complementary and provide strong synergy. Since 2015, the number of faculty working in the area of genome stability and cancer has increased from 20 to 38 members, from 14 departments and 3 schools within the University of Pittsburgh and a core group of 13 independent faculty laboratories housed within the HCC Building. GS members conduct cancer-focused research supported by $6.5M in total annual direct funding of which $2.8M is NCI funding, $3.4M is other peer-reviewed and $0.3M is non-peer-reviewed. From 2015-August 2019, GS members published 516 cancer-related publications representing 20% intra-programmatic, 40% inter- programmatic, and 69% inter-institutional collaborations.