Owen was a postdoctoral fellow at Cardiff University investigating the role of the APC gene in Wnt signalling and cancer. In 2005, he became a Junior Group Leader at the Cancer Research UK Beatson Institute, and in 2011 he was appointed the Institute's Deputy Director. In 2016, the Institute's Director, Professor Karen Vousden moved to the Francis Crick Institute and became CRUK's chief scientist, and Owen acted as interim Director of the Beatson Institute until being appointed as the next Director in 2017. He also leads the CRUK Glasgow Centre, which aims to bring together scientists and clinicians to work together on cancer research, drug discovery and patient care.
Research
The Phenotype of ''APC'' loss ''in vivo'' and key effector pathways
Owen was the first person to acutely delete the APC gene in the murine intestine, a model that he then used to elucidate the key pathways that APC controls in vivo. Using this model system, Owen's group identified critical functional roles for genes such as MYC, RAC and MTOR. Additionally, the use of this and other models has allowed Owen's group to identify potential chemoprevention strategies. For example, the group's work on aspirin showed that embryonic and perinatal exposure to aspirin suppresses neoplasia associated with the loss of Apc function.
Neutrophils in colorectal and other cancers
Owen's group showed that neutrophils are associated with the earliest stage of CRC, and using mouse models they showed that inhibition of the chemokine receptorCXCR2 could suppress both colitis and spontaneous cancer. This was confirmed by the Dubois group in 2013. Owen's group continued these studies into the pancreas to show that inhibition of CXCR2 suppresses metastasis in pancreatic cancer.
In collaboration with Hans Clevers's laboratory, Owen's group showed that Lgr5-positive cells are an efficient cell of tumourigenesis. Within the same study, they also showed that non-stem cells lacking APC could form lesions but would rarely progress. Following on from these studies, the group worked with Florian Greten's laboratory to show that additional mutations can cause an expansion in the cell of origin. This work built upon work in Owen's laboratory on understanding the cooperation of APC with mutations in other genes such as KRAS and PTEN.
Key regulators of metastasis
Owen's group has developed models of metastatic disease and identified critical components of the metastatic pathway, which has led to the design of trials specifically aimed at targeting metastatic disease in pancreatic cancer, e.g. Dasatanib in resectable pancreatic cancer patients. The group also provided definitive functional information on the role of mutant p53 in metastasis and mechanisms behind the process: integrin recycling, LOX, RHO The group also identified critical roles for RAC and its GEFs in melanoma migration and metastasis.
