Welcome to the Eck Lab

Structure and Mechanism in Cancer Signaling

We use biochemical and biophysical methods (including X-ray crystallography and cryo electron microscopy) to distill problems of central importance in cancer biology to their structural and mechanistic essentials. We are especially interested in the structure and regulation of kinases and their mutational activation in cancer, and in using structural approaches to facilitate development of anti-cancer drugs. The lab is located at the Dana-Farber Cancer Institute, and we are part of the Department of Biological Chemistry and Molecular Pharmacology at Harvard Medical School.

We have a long-standing focus on EGFR mutations in lung and other cancers, and have discovered mechanisms by which somatic mutations in the EGFR kinase domain lead to catalytic activation and also sensitize to EGFR-directed inhibitors. Additionally, we have dissected the mechanism of resistance of the EGFR T790M mutant and developed novel mutant-selective inhibitors that overcome this resistance.  More recently, we have elucidated the structural basis of BRAF autoinhibition, highlighting how BRAF is maintained in an autoinhibitted state in the absence of stimulatory extracellular signals. We have expanded on these mechanistic details of BRAF autoinhibition and activation to also study how current RAF inhibitors differentially affect each RAF isoform, and are working to develop novel small molecule RAF inhibitors as well . An additional interest in this area is the KIAA1549:BRAF fusion found in pediatric glioblastomas. We hope to exploit our evolving structural/biochemical dissection of this fusion oncogene to develop novel therapeutics.