Dr Catherine Hogan
Epithelial cells communicate and integrate multiple networks of signals through cell-cell interactions, which instruct cells on position, function and fate. Tight control of these processes is required to maintain homeostasis of a tissue. In the early stages of many human cancers, single cells sporadically acquire genetic mutations and become transformed. My research focuses on understanding how transformed cells expand to form precursor lesions within an environment of tightly regulated growth control and homeostasis, events that are poorly understood. I am particularly interested in the initial stages of human epithelial cancers where Ras mutations are one of the earliest events, such as pancreatic cancer. Using a combination of in vitro epithelial cell culture systems and in vivo mouse models, my research will explore the molecular and cellular mechanisms underlying how Ras-transformed and normal epithelial cells interact and communicate. I will also determine whether these cell-cell interactions promote or prevent expansion of the transformed cells. This may generate new and innovative insights into the early stages of epithelial cancers and advance the development of early detection, diagnostic and preventative strategies.
I completed my undergraduate training at my hometown university in Ireland, University College Cork, and then went on to do a research masters in Molecular Biology at the Royal College of Surgeons in Ireland and Trinity College Dublin. During my PhD I changed focus to study cell biology and imaging in the laboratory of Professor Gareth Jones at the Randall Division of Cell and Molecular Biophysics, King's College London. My thesis project described signalling from Rho GTPases to the actin cytoskeleton in macrophage migration and chemotaxis.
I joined the MRC Laboratory for Molecular Cell Biology (LMCB), University College London in 2003 as a MRC postdoctoral fellow in the laboratory of Dr Yasuyuki Fujita. Initially, my studies focused on the regulation of E-cadherin dynamics in epithelial cells, and later switched to understanding the interaction between transformed and normal epithelial cells. From 2011, I worked as an independent investigator scientist at the MRC LMCB, UCL. In September 2013, I joined the European Cancer Stem Cell Research Institute at Cardiff University as a Research Fellow.
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.
- Sean Porazinski (Research associate)
Postgraduate research students
- Professor Owen Sansom, Beatson Institute for Cancer Research, Glasgow
- Mr. Mark Duxbury's lab at the Translational Research Centre, University of Glasgow