Sleeping Beauty for cancer gene discovery

睡美人发现癌症基因

基本信息

批准号：
7676779
负责人：
Lara S Collier
金额：
$ 16.62万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-18 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7676779
关键词：
Ablation Address Allografting Androgens Antigen-Antibody Complex BRAF gene Biochemical Biological Assay Cancer Biology Cancer Center Cancer Model Candidate Disease Gene Cell Line Cell Survival Clinical Trials Cloning Complementary DNA Core Facility Cytogenetic Analysis DNA Disease Genes Genetic Genetic Screening Genomics Goals Health Hereditary Disease Hormones Human Laboratories Laboratory Research Localized Disease Malignant Neoplasms Malignant neoplasm of prostate Mass Spectrum Analysis Mediating Mentors Minnesota Modeling Morbidity - disease rate Mus Mutagens Mutate Mutation Oncogenes Oncogenic Orthologous Gene PC3 cell line Papillary thyroid carcinoma Patients Phosphotransferases Positioning Attribute Postdoctoral Fellow Radiation Refractory Relapse Research Residual Tumors Resistance Role Sampling Screening for cancer Sleeping Beauty Small Interfering RNA System Technology Testing Training Tumor Suppressor Proteins Tumor Volume Universities Work cancer genetics cancer initiation cancer therapy career chemotherapeutic agent drug discovery gene discovery hormone refractory prostate cancer inhibitor/antagonist kinase inhibitor member mouse model new technology novel outcome forecast pre-clinical professor programs research study sarcoma therapy resistant tumor tumor growth tumor progression

项目摘要

DESCRIPTION (provided by applicant): My primary research focus is to use a powerful novel insertional mutagen, the Sleeping Beauty (SB) transposon system, to address fundamental questions in cancer genetics. My training has previously focused on developing SB for forward genetic screens for cancer genes in mice. In my own research laboratory, I would like to pursue additional experiments studying the role of genes identified by SB in the context of human cancer, initially focusing on the BRAF oncogene. In addition, I would like to adapt the SB system to elucidate the genetics of a fundamental problem in human cancer treatment, namely therapy resistance. I propose to use the SB system to identify genes that are involved in acquired resistance to BAY 43-9006, a kinase inhibitor now showing promise in clinical trials as a chemotherapeutic agent. In addition, I propose to use the SB system to identify genes involved in prostate cancer progression as a result of acquired insensitivity to hormone ablation therapies. The role of identified genes in therapy resistance will be tested in human cancer models. These projects will be initiated in my final year as a post-doctoral fellow at the University of Minnesota. The SB system was originally developed for vertebrate genetics at the University of Minnesota, and my mentor's laboratory is a member of the Arnold and Mabel Beckman Center for Transposon Research. As a member of the Cancer Center, I have access to several Core facilities that will provide support to the projects proposed here. During my final year as a post-doctoral fellow, I will apply to assistant professor positions at Universities with strong research programs. My long-term career goal is to establish a research laboratory that uses novel genetic approaches to study human cancer biology and treatment. The proposed research employs a novel technology, the Sleeping Beauty transposon system, to identify genes involved in both cancer initiation and progression to therapy resistance. This research is relevant to human health as understanding the genetics of the disease is an important step toward developing more effective, patient-specific therapies. In addition, we hypothesize that this technology will be useful for creating better models of human cancer that will be useful for drug discovery and testing.

描述（由申请人提供）：我的主要研究重点是使用强大的新型插入诱变剂“睡美人（SB）Transposon系统”来解决癌症遗传学中的基本问题。我的培训以前一直集中在为小鼠的癌症基因的正向遗传筛查开发SB。在我自己的研究实验室中，我想进行其他实验，研究SB在人类癌症背景下鉴定的基因的作用，最初侧重于BRAF癌基因。此外，我想适应SB系统，以阐明人类癌症治疗中基本问题的遗传学，即耐药性。我建议使用SB系统来识别与获得43-9006 Bay抗性的基因，Bay 43-9006是一种激酶抑制剂，目前在临床试验中作为化学治疗剂表现出了希望。此外，我建议使用SB系统来鉴定因对激素消融疗法的不敏感性而导致的前列腺癌进展的基因。鉴定基因在治疗抗性中的作用将在人类癌症模型中进行测试。这些项目将在我的最后一年作为明尼苏达大学的博士后研究员开始。 SB系统最初是为脊椎动物遗传学开发的明尼苏达大学，我的导师实验室是阿诺德（Arnold）和梅贝尔·贝克曼（Mabel Beckman）跨盆地研究中心的成员。作为癌症中心的成员，我可以使用几个核心设施，这些设施将为这里提议的项目提供支持。在担任博士后研究员的最后一年中，我将申请具有强大研究计划的大学的助理教授职位。我的长期职业目标是建立一个研究实验室，该研究实验室使用新颖的遗传方法研究人类癌症生物学和治疗。拟议的研究采用了一种新颖的技术，即“睡美人转座子系统”，以识别涉及癌症启动和进展为抗治疗性的基因。这项研究与人类健康有关，因为了解该疾病的遗传学是发展更有效，特定于患者的疗法的重要步骤。此外，我们假设该技术将有助于创建更好的人类癌症模型，这将有助于药物发现和测试。