Investigating Resistance to FLT3 Inhibitors in AML

描述（由申请人提供）：该申请的主要目标是培养Smith博士，他是一名具有白血病临床转化研究潜力的候选人，能够有效地将基因组数据转化为功能研究，从而促进急性髓性白血病临床有效治疗方法的发展。该研究计划包括以下方面的培训目标：1)新兴基因组技术，特别是下一代测序数据的分析；2)生物化学和蛋白质组学；重点研究激酶功能和3)致癌信号传导和转化的细胞模型，通过以下科学目标：1)定义和验证与临床活性研究性FLT3抑制剂耐药相关的遗传变化；2)定义quizartinib耐药FLT3激酶结构域突变的分子影响。该应用程序结合了课程作业，教程，指导和直接的实验室研究经验，设置在UCSF无与伦比的科学环境中，UCSF是一个世界知名的研究机构，拥有完善的nci资助的综合癌症，多种机构资源和杰出的医生-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.