Timothy Burns, research and clinical interests revolve around the development of targeted therapies for KRAS-mutant NSCLC as well as novel strategies to overcome resistance to targeted therapies for EGFR-mutant and MET-altered NSCLC. My four main research themes are 1) novel pre-clinical target validation and drug development (TWIST1 in oncogene driven NSCLC and TKI resistance; targeting metabolism in oncogene driven lung cancer); and 2) elucidating mechanisms of resistance for targeted inhibitors to develop rationale therapeutic combinations that can be tested in the clinic (Hsp90, ERK1/2 inhibitors and 4th generation EGFR TKIs) and 3) development of targeted therapy approaches for the treatment of brain metastases.  The first line of research in my laboratory focuses on the role of the EMT transcription factor TWIST1 in oncogene-driven NSCLC. We have demonstrated the TWIST1 is essential for lung tumorigenesis for KRAS mutant, EGFR mutant and MET mutant/amplified NSCLC and TWIST1 overexpression leads to resistance to EGFR and MET TKIs. We are examining the mechanism(s) through which this occurs and developing therapeutic combinations to overcome this resistance. Importantly, we have developed a novel TWIST1 inhibitor which serves a tool compound for our therapeutic studies and serves as the basis for our current drug screening efforts to develop a clinical TWIST1 inhibitor. The second line of research in my lab focuses on studying the mechanisms of resistance to targeted agents currently in phase 1 and 2 trials to develop rationale therapeutic combinations in the clinic. This is typified by our previous work with Hsp90 inhibitors and ongoing work on ERK inhibitors and a novel 4th generation EGFR TKI.  Finally, my lab is interested in lung cancer brain metastases, and we are exploring whether targeting the HGF-MET-TWIST1 pathway or downstream metabolic pathways can be an effective strategy for preventing or treating lung brain metastases. In additional to these preclinical studies, we are using both radiogenomic and cell free DNA approaches to predict molecular phenotypes of brain metastases to identify patients with brain metastases that can benefit from MET targeted therapy in the clinic.