Cylcin G1/S Expression and Radiation Sensitivity

Cylcin G1/S 表达和辐射敏感性

• 批准号: 6685094
• 负责人: Francisco S Pardo
• 金额: $ 14.88万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-15 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6685094
• 关键词: DNA damage; DNA repair; DNA replication; apoptosis; cell cycle; cell growth regulation; cyclins; flow cytometry; gene expression; genetically modified animals; glia; ionizing radiation; laboratory mouse; protein structure function; radiation genetics; radiation sensitivity; tissue /cell culture; western blottings

DESCRIPTION (provided by applicant): The K-22 transition award mechanism is particularly suited to this physician-scientist at this point in the academic career trajectory. Together with a team of 3 basic science collaborators/mentors and various consulting experts, the applicant has an unusually rich environment upon which to draw. The UCSD Cancer Center provided space, equipment, and technical support for the applicant. The protected time away from clinical responsibilities will allow for publication, additional data gathering and analysis, and achievement of the realistic goal of being in a favorably competitive position for an R01 application by the end of the second year of the program as outlined. The limited postgraduate coursework will provide a unique opportunity to develop and apply mechanistic insight into the labwork. The K-22 translational award will enable this physician-scientist to compete successfully for independent advancement in a career combining basic science with a limited practice in academic radiation oncology. The central hypothesis is that significant complementation exists between cell cycle regulatory and DNA repair functions at G1 thru S phase (G1/S). Cyclin E function plays an important role in G1/S-phase mediated cell cycle control and DNA damage repair following IR, as reflected in the kinetics of the G1/S transition and the enhanced IR sensitivity parameters derived in the applicant's laboratory. To the extent present, cell cycle dependent cyclin E induced radiosensitization is, at least in part, influenced by expression of the S-phase DNA repair regulatory pathways involving Chk1, Mre-11, and Nbs-1. The proposed human glial tumor and murine transgenic radiation sensitivity experiments will likely develop a mechanistic understanding of the complementation between mammalian cell cycle and DNA repair pathways following ionizing IR-induced DNA damage thru G1/S. Furthermore, the rationale behind the analyses may have direct translational potential with respect to clinically relevant models of tumor initiation and radioresponse. Given the combination of strong interest in cell cycle regulation at G1/S, DNA repair following irradiation, intriguing radiobiologic glial and transgenic models of cyclin induction, and solid foundation in neurooncology, the applicant is well prepared to tackle these problems within the framework of the institutional resources and collaborative venues available at UCSD. The long-range goals are to formulate a mechanistic understanding of radiation sensitivity through potentially complementary mechanisms involving cell cycle regulation and the repair of radiation-induced DNA damage at G1 thru S phase (G1/S). Ultimately, it is hoped that the translation of such knowledge will enhance care in the radiation oncology clinic.

描述（由申请人提供）：K-22过渡奖励机制特别适合在学术生涯轨迹的这一点上的医生-科学家。与3名基础科学合作者/导师和多位咨询专家组成的团队一起，申请人拥有一个不同寻常的丰富环境。加州大学圣地亚哥分校癌症中心为申请人提供了场地、设备和技术支持。免受临床责任的保护时间将允许发表，额外的数据收集和分析，并实现在项目第二年末在R01申请中处于有利竞争地位的现实目标。有限的研究生课程将提供一个独特的机会来发展和应用机械洞察力到实验室工作。K-22转化奖将使这位内科科学家能够在将基础科学与学术放射肿瘤学的有限实践相结合的职业生涯中成功竞争独立进步。