How Oncogenic Mutations Reshape EGFR Family Receptor Assembly

Seminar Details

Host: Dr. Tatyana Igumenova

Time: 4:00pm-5:00pm

Location: BICH 108

Seminar Abstract

EGFR family receptor tyrosine kinases play central roles in development and cancer, yet fundamental questions remain about how these receptors assemble and signal at the plasma membrane. In particular, the relative contributions of homo- and heterodimerization, the impact of oncogenic mutations, and the role of the membrane environment itself are still incompletely understood. In this seminar, I will present recent work from our laboratory that uses quantitative live-cell membrane biophysics to dissect EGFR family receptor assembly and signaling under near-native conditions. Using pulsed interleaved excitation fluorescence cross-correlation spectroscopy (PIE-FCCS) and complementary biochemical reconstitution approaches, we directly measure receptor dimerization equilibria and kinetics in living cells and model membranes. Our results reveal that EGFR family heterodimerization is highly context-dependent and can be strongly reshaped by oncogenic mutations commonly found in cancer. We find that these mutations alter not only kinase activity, but also receptor assembly preferences that involve coupling between extracellular, transmembrane, and intracellular domains. In addition, we show that anionic membrane lipids act as active regulators of receptor signaling by modulating kinase activity and dimer stability, providing a previously underappreciated layer of control over signaling output. Together, these findings support a model in which EGFR family signaling is shaped by the integrated effects of receptor composition, oncogenic perturbations, and membrane electrostatics. This work highlights the importance of studying receptor tyrosine kinases in situ and suggests new avenues for targeting these receptors in cancer drug development.