TARGETING OF TRANSLOCATION TRANSCRIPTS IN LEUKEMIA

描述（申请人的描述）：本提案旨在使 博士Asad Bashey将花四年时间获得丰富的研究经验， 在大学Flossie Wong-Staal博士的指导下发展 来自加州圣地亚哥 巴什医生，他专门从事临床 血液学/肿瘤学和骨髓移植，有一些以前的 在癌症研究所的生物医学研究经验， 英国伦敦。 在那里，他获得了人类分子生物学方面的专业知识， 白血病与信号转导 他的工作产生了几个 出版物和博士学位℃下 在加州大学圣地亚哥分校，他完成了临床 培训并培养了对靶向嵌合基因产品的兴趣， 人类白血病使用核酶。 在王斯塔尔医生的监督下 他目前的目标集中在核酶的临床前开发上， 针对E2 A-PBX 1和BCR-ABL的RNA酶P外部指导序列 人类白血病中的嵌合转录物。 这些核酶将被优化 在这些白血病的体外和细胞培养物和动物模型中。 最 这些小RNA的有效递送手段和高水平表达 分子将被分析。 巴什博士的长期目标包括 他正在开发的治疗方式的临床应用， 实验室和扩大其使用到其他人类恶性肿瘤。 他将 继续探索新的治疗策略， 在了解恶性肿瘤的分子发病机制后。 博士 Wong-Staal的实验室一直是核酶开发的先驱 用于治疗人类疾病。 UCSD校园还将提供 几位重要的合作者和一位优秀的学者 环境，包括课程和研讨会博士巴希的发展， 独立调查员

DESCRIPTION (Applicant's Description): This proposal is designed to enable Dr. Asad Bashey to spend four years gaining intense research experience and development under the mentorship of Dr. Flossie Wong-Staal at the University of California, San Diego. Dr. Bashey, who has specialized in clinical hematology/oncology and bone marrow transplantation, has had some previous experience in biomedical research at the Institute of Cancer Research in London, UK. There he acquired expertise in the molecular biology of human leukemia and signal transduction. His work was productive of several publications and a Ph.D. degree. At UCSD he has completed his clinical training and developed an interest in targeting chimeric gene products in human leukemia using ribozymes. Under the supervision of Dr. Wong-Staal, his current goals focus upon the pre-clinical development of ribozymes and RNAse P external guide sequences directed against the E2A-PBX1 and BCR-ABL chimeric transcripts in human leukemia. These ribozymes will be optimized in vitro and in cell culture and animal models of these leukemias. The most effective means of delivery and high level expression of these small RNA molecules will be analyzed. Dr. Bashey's long term goals involve the clinical application of the therapeutic modalities he is developing in the laboratory and expanding their use to other human malignancies. He will continue to explore novel therapeutic strategies which are rationally based upon an understanding of the molecular pathogenesis of malignancy. Dr. Wong-Staal's laboratory has been pioneering in the development of ribozymes for the treatment of human disease. The UCSD campus will also provide several important collaborators for this proposal and an excellent academic environment including courses and seminars for Dr. Bashey's development into an independent investigator.