Lucet-Projects

Lucet-Projects

Researcher: 

Projects

Emerging role of transmembrane pseudokinases in cancer

A subset of Receptor Tyrosine Kinases (RTK) with intracellular pseudokinase domains, called RTK-like pseudokinases, have recently emerged as critical regulators of Wnt signalling pathway that regulates epithelial mesenchymal transition (EMT), a process that controls planar cell polarity, cell-cell adhesion and enables the initiation of metastasis for cancer progression. Despite lacking catalytic activities, RTK-like are thought to act as crucial modulators of bona fide RTKs. However the precise mechanism by which RTK-like orchestrate RTK activity remains largely elusive. We are using an integrated approach that includes targeted genome editing technologies, chemical biology and structural biology to fully elucidate the biological function of RTK-like pseudokinases during development and cancer.

Team members:
Dr Isabelle Lucet, Chemical Biology Division
Dr James Murphy, Cell Signaling and Cell Death Division

Investigating the role of the protein kinase DCLK1 in colorectal and pancreatic cancers

Doublecortin-like kinase 1 (DCLK1) has recently emerged as a tumor specific stem cell marker in colorectal and pancreatic cancers. While DCLK1 has been genetically validated using small interfering RNA (siRNA) as a therapeutic target, the direct effect of inhibiting DCLK1 kinase activity using small molecule inhibitors is yet to be investigated. 

We are combining cellular biology, chemical biology, kinase biochemistry and structural biology to develop small molecules that specifically target DCLK1. These compounds will be further examined in cellular assays to advance our understanding of the biological function of DCLK1 and its role in tumourigenesis.

Team members:
Dr Isabelle Lucet, Chemical Biology Division
Dr Michael Buchert, Cell Signaling and Cell Death Division