Investigating Resistance to FLT3 Inhibitors in AML

描述(由申请人提供)：拟议申请的广泛目标是将史密斯博士培养成一名独立的首席研究员，他是一名具有白血病临床翻译研究潜力的候选人，能够有效地将基因组数据的“床边到工作台”转换转换为功能研究，从而促进急性髓系白血病临床有效疗法的开发。该研究计划纳入了拟议的培训目标，即1)新兴基因组技术的使用，特别是下一代测序数据的分析，2)生物化学和蛋白质组学，重点是激酶功能的研究，以及3)通过以下科学目标建立致癌信号和转化的细胞模型：1)定义和验证与临床活性研究中的Flt3抑制剂耐药有关的基因变化；2)确定耐Quizartinib的Flt3激酶域突变的分子影响。该应用程序结合了课程作业、教程、指导和在加州大学旧金山分校无与伦比的科学环境中建立的直接实验室研究经验，加州大学旧金山分校是一家世界知名的研究机构，拥有由NCI资助的全面癌症，多种机构资源和杰出的内科科学家社区。

DESCRIPTION (provided by applicant): The broad goal of the proposed application is train Dr. Smith, a candidate with demonstrated potential as a clinical-translational researcher in leukemia into an independent principal investigator capable of effectively mediating the "bedside to bench and back" translation of genomic data into functional studies that will facilitate the development of clinically effective therapeutics for acute myeloid leukemia. The research plan incorporates the proposed training goals of education and experience in the use of 1) emerging genomic technologies, particularly analysis of next-generation sequencing data, 2) biochemistry and proteomics, with an emphasis on the study of kinase function and 3) cellular models of oncogenic signaling and transformation through the scientific aims of 1) defining and validating genetic changes associated with resistance to clinically active investigational FLT3 inhibitors and 2) defining the molecular impact of quizartinib-resistant FLT3 kinase domain mutations. The application incorporates a combination of coursework, tutorials, mentoring and direct laboratory research experience set in the unparalleled scientific environment of UCSF, a world-renowned research institution with a well-established NCI-funded Comprehensive Cancer, multiple institutional resources and a distinguished community of physician-scientists.