We are investigating the signalling processes that underpin cancer cell proliferation and survival. The EML4-ALK fusion oncoprotein is responsible for ~5% of non small cell lung cancer. We determined the structure of the trimerization domain of EML4, which is essential for oncogenic ALK signaling (Richards, Biochem J. 2015) and the structure of the TAPE domain of the related protein EML1 (Richards, PNAS 2014). Working with collaborators in Seoul, the structures helped to stratify EML4-ALK patients with variant forms of the fusion, revealing that a subset of patients respond poorly to therapy (Woo, Ann Oncol 2017; Sabir, Cancers 2017). The EML4-ALK variant in these patients promotes changes in microtubule organisation and cell migration through the NEK7 and NEK9 kinases (O’Regan, 2020).
