I am a basic science investigator, and my research is focused on receptor tyrosine kinase (RTK) signaling in human health and disease with an emphasis on epidermal growth factor receptor (EGFR) signaling. For my doctoral studies, I joined the lab of Prof. Axel Ullrich, where I uncovered the novel role of ultraviolet radiation in inducing EGFR activation via metalloprotease-mediated release of EGFR ligands. For my postdoctoral research, I joined the lab of Dr. Robert Coffey. Here, I undertook a comprehensive systematic analysis of trafficking three of the seven EGFR ligands in polarized epithelial cells that opened up new areas of cell biological investigation. I have shown that spatial cues to regulate EGFR signaling are best appreciated in Transwell cultures and three-dimensional (3D) cultures (e.g. type I collagen and MatrigelTM) than conventional 2D plastic cultures. Recently, a new direction as an independent investigator has been to study mechanism of cetuximab resistance using a new 3D culture system of colorectal cancer (CRC) cells; cetuximab is an FDA-approved EGFR neutralizing monoclonal antibody. Using this system, I have discovered two non-genetic modes of cetuximab resistance and identified means to overcome this resistance by addition of a multi-RTK inhibitor, crizotinib. I showed that crizotinib targets, MET and RON, are hyperactivated in this mode of cetuximab resistance. I am committed to elucidating the mechanistic underpinnings of this new mode of cetuximab resistance, its scope in human CRC, and the therapeutic benefit of combined blockade of EGFR with RTKs, MET and RON. This work has led to an investigator-initiated Phase I/II clinical trial at VUMC for panitumumab/crizotinib combination in advanced CRC (Drs. Kristen Ciombor and Jordan Berlin), and a collaborative pipeline with Vanderbilt Chemical Synthesis and Radiochemistry Cores for the synthesis and characterization of 18F-crizotinib as a rapid, non-invasive, quantitative, PET-based predictive biomarker of therapeutic response.