USC Norris Comprehensive Cancer Center (Core) Grant

 描述（由申请人提供）：自USC Norris在35年前首次获得NCI指定以来，分子遗传学计划一直通过NCI CCSG获得批准。该计划一直以其在DNA复制和DNA修复方面的实力而闻名全国，重点是将发现应用于癌症化疗。在项目期间，Preet Chaudhary与Michael Lieber一起担任联合负责人，以增加翻译的深度，并监督与HHV 8感染相关的癌症分子遗传学的新主题，包括开发治疗这些癌症的靶向疗法。该计划有三个综合目标：1）遗传不稳定性中的DNA复制，细胞周期和细胞增殖; 2）遗传不稳定性中的DNA修复和重组; 3）病毒肿瘤发生，重点是HHV 8。恶性淋巴瘤被用作项目成员用于所有三个目标的疾病模型。成员继续高度互动内和跨主题和跨程序的界限。来自三所学校和13个部门的39名计划成员拥有1140万美元的同行评审资金（直接成本），其中18%来自NCI，61%来自其他NIH来源，8%来自其他同行评审资金来源。该方案成果丰硕，出版了439份出版物，其中21%是方案间出版物，15%是方案内出版物，25%是机构间出版物。项目负责人每年组织几次务虚会和小型研讨会，在项目内部和项目之间进行交叉研究，同时保持警惕，以确保成员之间的高水平交流。这导致在确保新的方案内和方案间的P01方面取得了很大的成功，同时也贯穿各专题。例如，更新NCI P01以了解人类DNA聚合酶活性位点和开发新的化疗药物（Goodman，McKenna，Warshel），以及更新NCI P01以研究KSHV（HHV 8）的病毒致癌作用（Jung，Feng，Gao）。成员在寻求新的癌症药物疗法方面特别成功，这是通过转化和临床科学计划实现的。

 DESCRIPTION (provided by applicant): The Molecular Genetics Program has been continuously approved through the NCI CCSG since the USC Norris first received NCI designation over 35 years ago. This Program has always been distinguished nationally for its strength in DNA replication and DNA repair, with an emphasis on applying discoveries toward cancer chemotherapy. During the project period, Preet Chaudhary joined Michael Lieber as Co-Leader to add depth in translation and oversee a new theme on the molecular genetics of cancers associated with infection by HHV8, including the development of targeted therapies for the treatment of these cancers. The Program has three integrated aims: 1) DNA replication, cell cycle, and cell proliferation in genetic instability; 2) DNA repair and recombination in genetic instability; and 3) viral oncogenesis with an emphasis on HHV8. Lymphoid malignancies are used as a disease model used by Program members for all three aims. Members continue to be highly interactive within and across themes and across program boundaries. The 39 Program members, who come from three schools and 13 departments, have $11.4M in peer-reviewed funding (direct costs), of which 18% is from NCI, 61% from other NIH sources, and 8% from other peer-reviewed funding sources. The Program is highly productive with 439 publications of which 21% are inter-programmatic, 15% intra-programmatic and 25% inter-institutional. Program Leaders organize retreats and mini-symposia several times per year to cross-fertilize research within and across Programs while remaining watchful to ensure a high level of member crosstalk. This has led to high success in securing new P01s that are intra- and inter-programmatic, while also cross-cutting thematically. Examples include renewal of an NCI P01 on understanding human DNA polymerase active sites and development of new chemotherapeutics (Goodman, McKenna, Warshel), and a new NCI P01 on viral oncogenesis by KSHV (HHV8) (Jung, Feng, Gao). Members have been particularly successful in seeking new cancer drug therapies, which has been achieved with the Translational and Clinical Sciences Program.