Regulatory mechanisms in ROR1 receptor pseudokinase signaling – from conformational switching to novel therapeutic targeting

Around 10% of known kinases have mutations in the kinase domain expected to impair their catalytic activity and are termed pseudokinases. In this project we will investigate how ROR1 (receptor tyrosine kinase-like orphan receptor) receptor pseudokinase initiates molecular signaling in cancer cells. In healthy adult tissues, ROR1 expression is very low, however upregulation of ROR1 signaling is linked to tumorigenesis and drug-resistance. We aim to characterize the molecular mechanism associated with ROR1 signaling and how it is dysregulated in cancer. The results of this project are expected to be useful in designing new treatment options for all cancers that express ROR1.