USC Norris Comprehensive Cancer Center (Core) Grant

 描述(由申请人提供)：自35年前南加州大学诺里斯分校首次获得NCI称号以来，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修复方面的优势而在全国范围内享有盛誉，重点是将发现应用于癌症化疗。在项目期间，Preet Chaudhary加入Michael Lieber担任联合负责人，增加了翻译的深度，并监督了与HHV8感染相关的癌症的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)遗传不稳定中的DNA复制、细胞周期和细胞增殖；2)遗传不稳定中的DNA修复和重组；以及3)以HHV8为重点的病毒致癌。淋巴系恶性肿瘤被方案成员用作所有三个目标的疾病模型。成员继续在主题内部和跨主题以及跨计划边界进行高度互动。39名计划成员来自三所学校和13个部门，拥有1140万美元的同行审查资金(直接成本)，其中18%来自NCI，61%来自NIH的其他来源，8%来自其他同行审查的资金来源。该方案很有成效，有439种出版物，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。项目负责人每年都会组织几次务虚会和小型研讨会，以促进项目内部和跨项目的研究，同时保持警惕，以确保高水平的成员交流。这导致在获得方案内和方案间新的P01方面取得了很大的成功，同时也在主题上交叉。例如，更新了关于了解人类DNA聚合酶活性部位的NCI P01和开发了新的化疗药物(Goodman，McKenna，Warshel)，以及关于KSHV(HHV8)病毒致癌的新NCI P01(Jung，Feng，Gao)。成员们在寻求新的癌症药物疗法方面尤其成功，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.