Catherine Smith, MD

My laboratory focuses on identification of therapeutic resistance mechanisms and novel treatment strategies for acute myeloid leukemia (AML). We have a particular emphasis on AML associated with mutations in Fms-like Tyrosine Kinase-3 (FLT3). FLT3 is mutated in ~30% of AML, with constitutively activating FLT3 internal tandem duplication (ITD) mutations conferring a poor prognosis. We employ a prototypical “bedside to bench and back” approach to the problem of cancer drug resistance, founded on the belief that the ultimate pathway to improved cancer therapy begins with translational studies that utilize samples from patients who have undergone therapy in real time. This strategy allows us to interrogate how tumors can evolve under the selective pressure of cancer therapy and allows us to devise ways to circumvent these evolutionary adaptations.

We have the following specific research focuses at the current time:
1) Rational discovery and screening of novel FLT3 inhibitors coupled with analysis of resistance mechanisms to clinically relevant FLT3 inhibitors currently in clinical trials.
2) Identification and validation of non-FLT3 dependent mechanisms of FLT3 inhibitor resistance through genomic analysis of patients treated on FLT3 inhibitor clinical trials.
3) Study of the role of AML genetic tumor heterogeneity in response and resistance to FLT3 inhibitor therapy.
4) Understanding the molecular mechanism of recurrent cyclin D3 mutations in mediating resistance to FLT3 inhibitor therapy.