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Dr Catherine Hogan 


My research focuses on understanding early tumorigenesis in epithelial tissues; how transformed cells expand to form precursor lesions within an environment of tightly regulated growth control and homeostasis, events that are poorly understood. I have examined and characterised the effect of expressing constitutively active oncogenic Ras (RasV12) in single cells within normal epithelial cell sheets (Hogan et al., Nature Cell Biol. 2009). This revealed that interaction with normal neighbouring epithelial cells controls the behaviour and fate of transformed cells within epithelial tissues, suggesting that for a tumour to initiate and develop, transformed cells may have to overcome the suppressive barrier imposed by normal cells. This has a profound impact on our current understanding of how oncogenes transform cells, and on how transformed cells expand to form a tumour within a normal epithelium. A major focus of my research will explore the mechanisms governing how normal cells communicate with mutant cells, and determine whether cell-cell interaction between Ras-transformed and normal cells plays a role during early development of pancreatic cancer. 

Pancreatic ductal adenocarcinoma (PDAC) arises from precursor lesions called pancreatic intraepithelial neoplasms (PanINs). Mutations that result in constitutively active KRas (KRasD12) occur as an initiating event in PanIN formation and are detected in > 90% of human PDAC. By investigating the cellular processes that arise once KRasD12 is expressed, we will generate for the first time, kinetic and real time analyses of PanIN initiation. This will lead us to identify the mechanisms controlling this process, thus advancing the development of new methods to detect PanINs at the earliest time points and prevent disease progression. 

Group Members

Sean Porazinski (Research associate)

Postgraduate Research Students 

Mr William Hill

Collaborations

Professor Owen Sansom, Beatson Institute for Cancer Research, Glasgow.

Mr. Mark Duxbury’s lab at the Translational Research Centre, University of Glasgow