Sleeping Beauty for cancer gene discovery

睡美人发现癌症基因

基本信息

批准号：
7674415
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/7674415
关键词：
Ablation Address Allografting Androgens Antigen-Antibody Complex BAY 43-9006 BRAF gene Biochemical Genetics 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 Prostate 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 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一种强大的新型插入诱变剂，即睡美人（SB）转座子系统，来解决癌症遗传学中的基本问题。我之前的培训重点是开发 SB，用于小鼠癌症基因的正向遗传筛选。在我自己的研究实验室中，我想进行更多实验，研究 SB 识别的基因在人类癌症中的作用，最初关注 BRAF 癌基因。此外，我想调整 SB 系统来阐明人类癌症治疗中一个基本问题的遗传学，即治疗耐药性。我建议使用 SB 系统来识别与 BAY 43-9006 获得性耐药相关的基因，BAY 43-9006 是一种激酶抑制剂，目前在临床试验中显示出作为化疗药物的前景。此外，我建议使用 SB 系统来识别因对激素消融疗法获得性不敏感而导致前列腺癌进展的相关基因。已确定的基因在治疗抵抗中的作用将在人类癌症模型中进行测试。这些项目将在我作为明尼苏达大学博士后研究员的最后一年启动。 SB 系统最初是为脊椎动物遗传学而开发的明尼苏达大学，我导师的实验室是阿诺德和梅布尔贝克曼转座子研究中心的成员。作为癌症中心的成员，我可以使用多个核心设施，这些设施将为此处提出的项目提供支持。在博士后的最后一年，我将申请具有强大研究项目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，利用新颖的遗传方法来研究人类癌症生物学和治疗。拟议的研究采用了一种新技术，即“睡美人转座子系统”，来识别与癌症发生和进展为治疗耐药性相关的基因。这项研究与人类健康相关，因为了解该疾病的遗传学是开发更有效、针对患者的疗法的重要一步。此外，我们假设这项技术将有助于创建更好的人类癌症模型，从而有助于药物发现和测试。