Cellular and Molecular Tumorsuppressor Processes Uncovered by DNA Fork Protection

DNA 叉保护揭示细胞和分子肿瘤抑制过程

• 批准号: 8488140
• 负责人: Katharina Schlacher
• 金额: $ 20.01万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8488140
• 关键词: Accounting; Aplastic Anemia; Area; Award; BRCA1 gene; BRCA2 gene; CCL4 gene; Cell physiology; Cells; Commit; Critiques; DNA; DNA Damage; DNA Double Strand Break; DNA Repair; DNA biosynthesis; DNA replication fork; Data; Disease; Double Strand Break Repair; Engineering; Environment; Faculty; Fanconi Anemia-BRCA Pathway; Fanconi anemia protein; Fanconi' s Anemia; Filament; Funding; Genes; Genomic Instability; Genomics; Goals; Health; Heart; Hereditary Breast Carcinoma; High-Risk Cancer; Individual; Knowledge; Malignant Neoplasms; Mammary Neoplasms; Mediating; Memorial Sloan-Kettering Cancer Center; Mentors; Mentorship; Methods; Molecular; Mutate; Pathway interactions; Patients; Positioning Attribute; Principal Investigator; Process; Proteins; Public Health; RAD51C gene; Replication-Associated Process; Research; Research Personnel; Role; Secure; Structure; Technology; Testing; Therapeutic; Training; Tumor Biology; Tumor Cell Biology; Tumor Suppressor Proteins; United States National Institutes of Health; Writing; anticancer research; career; crosslink; experience; frontier; homologous recombination; improved; insight; malignant breast neoplasm; meetings; neoplastic cell; novel; nuclease; ovarian neoplasm; pancreatic neoplasm; paralogous gene; prevent; programs; public health relevance; repaired; stem cell biology; symposium; tumor; tumorigenesis

DESCRIPTION (provided by applicant): The applicant, Katharina Schlacher, is committed to a lifelong academic career and aims to become an independent investigator and enabling mentor at the frontier of cancer research in the field of replication fork protection. Katharina proposes three-year plan that will optimally equip her to becoming a successful independent research investigator in this challenging funding environment. The proposed project seeks to study cellular and molecular processes of replication fork protection by tumor-suppressor. The specific aims of the project are as follows: Aim1 Investigating replication fork instability in tumor cells, Aim2 Testing FA-mediated replisome stability, and Aim3 Determining RAD51 paralog tumor suppressor functions during fork protection. The proposed Aims will obtain critical knowledge on the impact of this new area of research to tumor biology, to understand its role in tumor cells and to initiate detailed insights into fork protection. This project will strengthen her abilities nd this new research area that is at the heart of her independent career, during which she aspires to decipher the mechanism of replication fork protection, identify new players of this pathway and open doors to understanding its implications with regards to stem cell biology and therapeutic strategies Under the mentorship of Dr. Maria Jasin (MSKCC) and co-mentor Dr. Hong Wu (UCLA), the candidate will meet regularly with her mentors, interact with other pertinent experts in the field, and supplement her training with structured meetings, conferences, and coursework. The award will produce sufficient preliminary data for independent funding applications, and enable her to acquire key technical knowledge, experience, and data needed to build and substantiate this new research area, to successfully jump-start her independent career and to secure an independent faculty position in health-related research. She will gain key extra and complementary experience in IPOND, Rad51 paralogs, and Talen technology for genomic engineering as well as on replication fork instability in mammary, ovarian and pancreatic tumor cells. Dr. Schlacher and her mentors thus view this project as a critical enabling opportunity for her to meet the challenges of her research goals and aspirations.

描述(由申请人提供)：申请者凯瑟琳娜·施拉赫致力于终身学术生涯，目标是成为复制叉子保护领域癌症研究前沿的独立研究员和使能导师。Katharina提出了三年计划，这将使她在这个充满挑战的资金环境中成为一名成功的独立研究调查员。这项拟议的项目旨在研究肿瘤抑制因子对复制叉保护的细胞和分子过程。该项目的具体目标如下：AIM1研究肿瘤细胞中的复制叉不稳定性， AIM2检测FA介导的复制体稳定性，Aim3检测RAD51类肿瘤抑制因子在分叉保护过程中的功能。拟议的目标将获得关于这一新研究领域对肿瘤生物学的影响的关键知识，了解其在肿瘤细胞中的作用，并启动对叉子保护的详细见解。这个项目将加强她在这个新的研究领域的能力，这是她独立职业生涯的核心，在此期间，她渴望破译复制叉子保护的机制，识别这条途径的新参与者，并打开大门，了解其对干细胞生物学和治疗策略的影响。在玛丽亚·贾辛博士(MSKCC)和共同导师吴宏博士(UCLA)的指导下，候选人将定期与她的导师会面，与该领域的其他相关专家互动，并通过有组织的会议和课程工作补充她的培训。该奖项将为独立资助申请提供足够的初步数据，并使她能够获得建立和充实这一新研究领域所需的关键技术知识、经验和数据，以成功启动她的独立职业生涯，并确保她在与健康相关的研究中获得独立教职。她将在iPOND、RAD51 Paralog和Talen基因组工程技术以及乳腺、卵巢和胰腺肿瘤细胞复制叉不稳定性方面获得关键的额外和补充经验。因此，Schlacher博士和她的导师们认为这个项目是她迎接研究目标和抱负的挑战的一个关键的有利机会。