Dissection of microRNA-21s role in non-small cell lung cancer

项目概要/摘要 该提案描述了为过渡期量身定制的基础研究培训计划 从博士后到独立研究员首席调查员有一个 博士在细胞调节，完成了结构化的住院医师培训计划在儿科 并即将完成儿科临床奖学金培训 血液学/肿瘤学。 本文所述的建议将促进对microRNA-21（miR-21）的控制。 非小细胞肺癌（non-small cell lung cancer，NSCLC）的发病机制在这方面，Eric博士 奥尔森是德克萨斯大学西南分校分子生物学的主席， 世界上关于微小RNA和疾病的小鼠模型的权威将成为一个理想的 导师他在过去培养了许多博士后研究员，并赞助了 以前和现在的科学家。为了加强培训，该计划将 约翰·明纳博士，内科和药理学教授的专业知识 肺癌分子基础方面的专家Luis Parada博士， 发育生物学是一位杰出的癌症生物学家和老鼠遗传学家，乔治博士 利斯特儿科主任此外，该咨询委员会不仅将 定期对数据、假设和拟议的实验提出建设性的批评， 关于职业发展的宝贵建议，作为一个独立的和富有成效的 医学科学家预计咨询委员会成员还将 在提供他们的专业知识和独特的试剂，以促进研究计划是无价的。 这项研究将侧重于阐明这种作用的分子机制。 miR-21在非小细胞肺癌进展中的作用最近在Olson的工作 实验室已经确定，miR-21表达可以调节NSCLC的进展， NSCLC的小鼠模型。拟议的实验将建立在这一观察的基础上 利用转基因小鼠模型和来自这些模型的肿瘤细胞系， miR-21在肺癌中的重要性以及miR-21 非小细胞肺癌的治疗方法具体目标包括：1） 确定miR-21在体内NSCLC发展中的作用，2）定义机制 3）探索miR-21抑制 作为NSCLC的治疗方法。这将是第一个详细的miR-21体内功能分析 使用癌症小鼠模型和功能获得性和功能丧失性miR-21 转基因小鼠 分子生物学系和NCI-Cancer Center的结合， UT西南提供了一个理想的环境，为培训医生，科学家， 将来自不同资源的专业知识纳入定制计划。这 环境将提供理想的跨学科环境，不仅可以进行 提出的实验，但作为一个独立的临床科学家， 学术生涯是可以构建的。

Project Summary/Abstract This proposal described a tailored basic research training program for the transition from post-doctoral fellow to independent investigator. The principle investigator has a Ph.D. in Cell Regulation, completed a structured residency training program in Pediatrics and is near the completion of clinical fellowship training in Pediatric Hematology/Oncology. The proposal described herein will foster a command on microRNA-21's (miR-21) role in the progression of non-small cell lung cancer (NSCLC). In this regard, Dr. Eric Olson the chairman of Molecular Biology at the University of Texas Southwestern and a world's authority on mouse models of microRNA and disease will serve as an ideal mentor. He has trained numerous post-doctoral fellows in the past and has sponsored previous and current physician scientists. To enhance the training, the program will enlist the expertise of Dr. John Minna, Professor of Internal Medicine and Pharmacology an expert in the molecular basis of lung cancer, Dr. Luis Parada, Chairman of Developmental Biology a premier cancer biologist and mouse geneticist, and Dr. George Lister, Chairman of Pediatrics. Furthermore, this advisory committee will not only provide regular constructive criticism of data, hypotheses, and proposed experiments but invaluable advice regarding career development as an independent and productive physician scientist. It is also expected that the members of the advisory committee will be invaluable in offering their expertise and unique reagents to foster the research plan. The research will focus on elucidating the molecular mechanisms underlying the role of miR-21 in the progression of non-small cell lung cancer. Recent work in the Olson laboratory has established that miR-21 expression modifies the progression of NSCLC in a mouse model of NSCLC. The proposed experiments will build on this observation utilizing transgenic mouse models and tumor cell lines from these models to determine the importance of miR-21 in lung cancer and the mechanism through which miR-21 contributes to non-small cell lung cancer development. The specific aims include: 1) Determine the role of miR-21 in development NSCLC in vivo, 2) Define the mechanisms responsible for miR-21 promotion of NSCLC pathogenesis, 3) Explore miR-21 inhibition as therapy for NSCLC. This will be the first detailed functional analysis of miR-21 in vivo using a mouse model of cancer and gain-of-function and loss-of-function miR-21 transgenic mice. The combination of the Molecular Biology Department and the NCI-Cancer Center at UT Southwestern provides an ideal setting for training physician-scientist by incorporating expertise from diverse resources into customized programs. This environment will provide the ideal interdisciplinary setting not only to conduct the proposed experiments but to develop as an independent clinician scientist from which an academic career can be constructed.