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: 8635320
• 负责人: Katharina Schlacher
• 金额: $ 6.08万
• 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 2014-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8635320
• 关键词: Accounting; Aplastic Anemia; Area; Award; BRCA1 gene; BRCA2 gene; CCL4 gene; Cell physiology; Cells; Commit; 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; Knowledge; Malignant Neoplasms; Mammary Neoplasms; Mediating; Memorial Sloan-Kettering Cancer Center; Mentors; Mentorship; Methods; Molecular; Mutate; Pathway interactions; Patients; Positioning Attribute; 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; 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; repaired; stem cell biology; symposium; tumor; tumorigenesis; Accounting; Aplastic Anemia; Area; Award; BRCA1 gene; BRCA2 gene; CCL4 gene; Cell physiology; Cells; Commit; 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; Knowledge; Malignant Neoplasms; Mammary Neoplasms; Mediating; Memorial Sloan-Kettering Cancer Center; Mentors; Mentorship; Methods; Molecular; Mutate; Pathway interactions; Patients; Positioning Attribute; 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; 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; 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）：申请人Katharina Schlacher致力于终身学术生涯，并旨在成为独立的研究者，并在复制叉保护领域的癌症研究领域的指导者成为指导。 Katharina提出了为期三年的计划，该计划将使她在这个充满挑战的资金环境中成为成功的独立研究调查员。拟议的项目旨在研究通过肿瘤抑制剂保护复制叉保护的细胞和分子过程。该项目的具体目的如下：AIM1研究肿瘤细胞中的复制叉不稳定性， AIM2测试FA介导的重置体稳定性，AIM3在叉子保护过程中确定RAD51旁系同源物抑制剂功能。拟议的目标将获得有关这一新研究领域对肿瘤生物学的影响的关键知识，以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。该项目将增强她的能力和这个新的研究领域，这是她独立职业的核心，在此期间，她渴望解释复制叉保护的机制，确定这一途径的新参与者，并开放的大门可以理解其对干细胞生物学和治疗策略在玛丽亚·杰西斯（Maria Jasin）的指导下（MSKCC）（MSKCC）的指导下（MSKCC）的指导（MSKCC）博士（MSKCC）博士（MSKCC）博士（MSKCC）博士（MSKCC）。导师，与该领域的其他相关专家互动，并通过结构化会议，会议和课程来补充她的培训。该奖项将为独立资金应用程序提供足够的初步数据，并使她能够获得建立和证实这一新研究领域所需的重要技术知识，经验和数据，以成功地启动她的独立职业，并确保与健康相关的研究中的独立教师职位。她将获得IPOND，RAD51旁系同源物和TALEN技术的主要额外和互补经验，用于基因组工程，以及在乳腺，卵巢和胰腺肿瘤细胞中的复制叉不稳定性。因此，施拉赫（Schlacher）和她的导师将该项目视为她的研究目标和愿望挑战的重要机会。