Investigating Resistance to FLT3 Inhibitors in AML

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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.