Genome Stability Program

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 基因组的完整性，这些过程在癌细胞中是如何改变的，最后这些改变可能是如何 被用来杀死肿瘤细胞。这个计划有四大主题：(1)基因组稳定的机制，(2) 辐射和氧化损伤，(3)遗传毒性应激反应，(4)衰老和癌症。基本原理 对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的靶点和策略的宝贵来源。 该计划的重要亮点是关于DNA修复行动的开创性发现 在蛋白质单分子水平上，利用靶向氧化损伤端粒进行研究 继发性端粒功能障碍，替代延长的端粒(ALT)途径在 侵袭性神经母细胞瘤，减轻辐射损伤的方法的发展，机制 对包括铁下垂在内的细胞死亡途径的洞察，以及ATR抑制剂与电离的联合使用 放射或顺铂通过增强免疫反应杀死肿瘤细胞。的增长和影响 通过从匹兹堡大学招聘18名新教师，该计划得到了极大的加强 通过美国癌症委员会支持的招募。该项目由Patricia Opresko博士和Bennett Van共同执导 侯腾博士。奥普雷斯科博士是一名环境和职业健康教授，在国际上 因她在端粒生物学的分子洞察力方面的工作而受到认可，并提供了到基因组的重要链接 稳定计划(GS)和集水区科学家。范豪腾博士是理查德·M·赛尔特教授 他是药理学和化学生物学系分子肿瘤学的专家，也是 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。 并提供强大的协同效应。自2015年以来，在基因组稳定和研究领域工作的教职员工数量 癌症从20名成员增加到38名成员，来自加州大学的14个系和3个学院 匹兹堡大学和一个由13个独立教员实验室组成的核心小组位于HCC大楼内。GS 成员开展癌症研究，每年直接资助650万美元，其中280万美元 是NCI的资金，340万美元是其他同行审查，30万美元是非同行审查。2015-2019年8月，GS 成员发表了516份与癌症有关的出版物，占方案内的20%，方案间的40% 方案，以及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.