TARGETING OF TRANSLOCATION TRANSCRIPTS IN LEUKEMIA

描述(申请人描述)：本提案旨在实现 阿萨德·巴希博士将花费四年时间获得紧张的研究经验和 在大学黄士达博士的指导下发展 加利福尼亚州的圣地亚哥。贝西医生，他专门从事临床研究 血液学/肿瘤学和骨髓移植，以前有一些 年在癌症研究所从事生物医学研究的经验 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 白血病和信号转导。他的工作取得了几项成果 出版物和博士学位。在加州大学圣地亚哥分校，他完成了他的临床 培训并培养了对嵌合基因产物靶向的兴趣 使用核酶治疗人类白血病。在黄士达博士的督导下， 他目前的目标集中在核酶和核酶的临床前开发。 针对E2a-Pbx1和bcr-abl的RNaseP外引导序列 人类白血病中的嵌合转录本。这些核酶将被优化 在这些白血病的体外、细胞培养和动物模型中。最多的 这些小RNA的有效传递方式和高水平表达 将对分子进行分析。巴希博士的长期目标包括 他正在开发的治疗方法在临床上的应用 实验室，并将其应用于其他人类恶性肿瘤。他会的 继续探索基于理性的新的治疗策略 在了解恶性肿瘤的分子发病机制的基础上。Dr。 Wong-Staal的实验室一直是开发核酶的先驱 用于治疗人类疾病。加州大学圣迭戈分校的校园还将提供 这项提议的几位重要合作者和一位优秀的学者 环境，包括课程和研讨会，让贝希博士发展成为 一名独立调查员。

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.