One of our research goals is to understand how EGFR-family proteins interact at the cellular level. EGFR is overexpressed in tumor tissue and up to 30% of all non-small cell lung carcinomas harbor mutations in the EGFR gene. We have resolved the effect of several EGFR mutants on protein structure and function. Our current goal is to systematically measure EGFR-family interactions and determine how these receptors respond to different cellular environments and oncogenic mutations. This work will add critical insight into the ongoing development of bispecific antibodies and antibody-drug conjugates, which are the next frontier of lung-cancer therapy.

• Brown, B. P.; Zhang, Y. K.; Kim, S.; Finneran, P.; Yan, Y.; Du, Z.; Kim, J.; Hartzler, A. L.; LeNoue-Newton, M. L.; Smith, A. W.; et al. Allele-specific activation, enzyme kinetics, and inhibitor sensitivities of EGFR exon 19 deletion mutations in lung cancer. Proc Natl Acad Sci USA 2022, 119 (30), e2206588119. DOI: https://doi.org/10.1073/pnas.2206588119

• Du, Z.; Brown, B. P.; Kim, S.; Ferguson, D.; Pavlick, D. C.; Jayakumaran, G.; Benayed, R.; Gallant, J. N.; Zhang, Y. K.; Yan, Y.; et al. Structure-function analysis of oncogenic EGFR Kinase Domain Duplication reveals insights into activation and a potential approach for therapeutic targeting. Nat Commun 2021, 12 (1), 1382. DOI: https://doi.org/10.1038/s41467-021-21613-6