Professor Joseph Slupsky B.Sc., Ph.D.

Personal Statement

The work of my group is focused on understanding the pathophysiological events that give the malignant cells in chronic lymphocytic leukaemia (CLL) and other B cell lymphomas their growth advantage. We are principally interested in understanding the regulation of signalling from the B cell antigen receptor (BCR). We have established a clear proximal role for the src-family kinase LCK in CLL cells where it initiates signalling in response to BCR engagement. We are also interested in the role of protein kinase CβII (PKCβII) in CLL. This kinase is important because it contributes to modulating BCR signal strength through its role in regulating the function of Bruton's tyrosine kinase (BTK), a principle mediator of BCR signalling. CLL cells also express very high levels of PKCβII. We are working together with Dr. Nagesh Kalakonda within this Department to understand how expression of the gene coding for PKCβII (PRKCB) is regulated during B cell differentiation and how this expression changes when cells become neoplastic, and with Dr. Alison Michie of the University of Glasgow to understand the functional role of overexpressed PKCβII. Finally, we have a collaborative project with Professors Ian Prior and Dave MacEwan at the University of Liverpool to use a kinomic approach to analyze the adaptations that occur in leukaemia cells in order to accommodate the events that contribute to their malignant behaviour. In particular, we are interested in understaning how cancer cells become resistant to chemotherapies that target BTK.