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Catherine Hogan

Dr Catherine Hogan

Lecturer

School of Biosciences

Email
HoganC@cardiff.ac.uk
Telephone
+44 29206 88505
Campuses
Hadyn Ellis Building, Room European Cancer Stem Cell Research Institute, Cardiff School of BiosciencesHadyn Ellis Building, Maindy Road, Cardiff CF24 4HQ, Maindy Road, Cardiff, CF24 4HQ
Users
Available for postgraduate supervision

Overview

Research overview

Epithelial homeostasis is fundamental to health and survival. Tissue health is maintained via processes that regulate the number and fitness of cells in tissues. This ensures that aberrant or mutant cells, which would otherwise cause disease are removed. Cell competition describes a general process whereby cells compete with its neighbour for space and survival and ‘loser’ cells are eliminated. Therefore, only cells of the highest quality contribute to a tissue. We currently lack a clear understanding of how healthy cells identify and detect ‘loser’ cells, particularly in highly organised complex tissues. Our research suggests that early tumour formation only occurs when cell competition fails or when the balance of the competition tips in favour of the tumour cells. Our goal is to define what regulates cell competition in healthy epithelial tissues and determine how tumour cells override this process to form a tumour. Our research will improve our understanding of the biology underlying how epithelial tissues maintain health. Equally, we will gain new insights into the biology and timing of early tumorigenesis. Together, this new knowledge will underpin the development of early detection cancer strategies and improve patient prognosis.

Publication

2024

2022

2021

2019

2016

2012

2011

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2003

Articles

Research

Research programme

We combine innovative and powerful in vitro epithelial cell systems, ex vivo organoid models and in vivo mouse models of cancer. We employ cutting-edge immunofluorescence techniques, including Lightsheet imaging of cleared tissues, and image analysis platforms to generate powerful 3D landscapes of labelled tissues. We combine these technologies with transcriptomics to uncover transcriptional signatures of cell competition in tissues. Through interdisciplinary collaboration, we apply mathematical modelling to test hypotheses and gain mechanistic insight and use Drosophila melanogaster models to scrutinise the role of key signalling pathways at the genetic level in vivo.

Cell competition in epithelial health and disease

We identified EphA2 (a receptor tyrosine kinase of the Eph-ephrin family of bidirectional signals) as an evolutionarily conserved signal that triggers the expulsion of RAS-transformed cells from tissues in vivo. Current projects in the lab are exploring the generality of this EphA2-dependent mechanism in epithelial tissues where oncogenic RAS is a key driver mutation. We also investigate the molecular mechanisms downstream of EphA2 as a regulator of epithelial tissue health.

Unravelling the biology of early pancreatic cancer

Pancreatic cancer is a devastating disease because we are unable to detect it at early stages when clinical intervention would vastly improve patients’ lives. Early detection is vital to improve patient prognosis. Pancreatic tumours start from cells expressing oncogenic Kras mutations (KRasG12D). Our research demonstrates that KrasG12D cells are outcompeted and eliminated from healthy pancreas tissues in vivo and this is tumour preventative. Current projects in the lab are investigating how KRasG12D cells override cell competition mechanisms, avoid cell elimination and remain in tissues to drive early disease.

Team members

Dr Beatriz Salvador

Dr Markella Alatsatianos

Liam Hill (PhD student)

Joshua D’Ambrogio (PhD student)

Anna Richards (PhD student; co-supervisor)

Collaborators:

Professor Richard Clarkson (ECSCRI).

Professor Alan Parker (MEDIC).

Professor Ann Ager (MEDIC).

Dr Thomas Woolley (MATHS).

Dr Ian Fallis (CHEMY).

Dr Lee Parry (ECSCRI).

Professor Paul Dyson (Swansea University).

Professor Owen Sansom (CRUK Beatson Institute, Glasgow).

Professor Jennifer Morton (CRUK Beatson Institute, Glasgow).

Professor Daniel Murphy (CRUK Beatson Institute, Glasgow).

Professor Eric O’Neill (Oxford University).

Professor Anne Grapin-Botton (Max Plank Institute MCBG, Dresden).

Dr Joaquin de Navascués (Essex University).

Teaching

Lecturer in Biomedical sciences.

Cell biology.

Cancer: Cellular and molecular mechanisms and therapeutics.

Advanced Research Methods & Project.

Contributor to Concepts in Disease and Skills for Science

Biography

Lecturer in Biomedical Sciences, School of Biosciences since Sept 2020. I joined the European Cancer Stem Cell Research Institute (ECSCRI) as Research Fellow in 2013. Postdoctoral training in the laboratory of Dr Yasuyuki Fujita at MRC Laboratory for Molecular Cell Biology (LMCB), University College London. I carried out my PhD training in the laboratory of Professor Gareth Jones at the Randall Division of Cell and Molecular Biophysics, King's College London.

Committees and reviewing

Grant reviewer: UKRI (MRC, BBSRC), CRUK, Breast Cancer Now.

Journal reviewer: Current Biology, Nature Communications, Developmental Biology, Disease Models & Mechanisms, Scientific reports, Breast Cancer Research, Biochemical journal.

Supervisions

Epithelial cell biology;

Quantitative image analysis and computational biology;

Early tumorigenesis in epithelial tissues.

Epithelial cell biology;

Quantitative image analysis and computational biology;

Early tumorigenesis in epithelial tissues.