Professor Eugenia Piddini
Welcome to the Piddini Cell Competition Laboratory
The Piddini Lab is interested in understanding the rules that govern the colonization of tissues by cellular communities. The group studies how cells compete for space and survival within tissues. Through a process known as cell competition, cells communicate and this determines which cells survive and colonise a tissue and which cells are removed through apoptosis or differentiation. The Piddini group studies the mechanisms of cell competition, its involvement in diseases like cancer and how it can be used to develop novel therapies in oncology and in regenerative medicine.
Cell competition is a fundamental biological process akin to natural selection at the cellular level.
Through cell competition relatively less fit cells (losers) are eliminated by fitter cells (winners) and this acts as a quality control mechanism to maximize tissue and organism fitness. Our work aims to understand the importance of cell competition in controlling tissue colonization in health and disease.
We and others have recently shown that cell competition plays an important role in shaping tissue colonization in adult homeostatic tissues. We have shown that cell competition promotes the expansion of healthy cells and the progressive killing of cells carrying disease-bearing mutations, allowing healthy tissue to progressively replace the unhealthy one. This lends support to the long-standing idea that, by eliminating subfit/damaged cells as they arise, cell competition may delay the onset of disease and potentially ageing. In addition, it further suggests that cell competition could be harnessed to boost the replacement of diseased cells with therapeutic cells in cell-based therapies.
However, cell competition can also promote disease. Using the fruit fly, a very powerful genetic model organism to study tumorigenesis, our group has shown that tumour cells compete with and kill host cells. We have then gone on to show that this process fuels tumour growth. Indeed we have been able to contain growth of these tumours by protecting healthy cells from cell competition and from being killed by the tumour. This suggests that empowering the host tissue to withstand tumour-host cell competition might offer a novel angle to counter tumour growth.
Mission and Impact
We aim to identify strategies to exploit cell competition in order to develop novel therapeutic approaches in cancer and in regenerative medicine.
Our lab uses several complementary model systems to study cell competition. We exploit Drosophila for mechanistic discovery - given its unique power to enable fast, cheap, in vivo research in a superiorly tractable genetic system. We use mouse and human cells in culture, both primary cells and cell lines, as a fully controllable and complementary cell biological platform. We combine a variety of approaches and technologies, including developmental, cell and molecular biology, genetics, gene editing, genetic screening both in vivo and in vitro and live imaging.
Currently, our team is addressing a number of questions:
- Mechanical cell competition. We recently showed that cells can compete via mechanical insults, a type of cell competition that we have named mechanical cell competition. In mechanical cell competition the tumour-suppressor p53 confers upon cells hypersensitivity to crowding and causes the elimination of cells by cells with lower p53 levels. Given the involvement of p53, Mechanical Cell Competition may be relevant to cancer. We are now investigating how p53 confers hypersensitivity to crowding.
- Nrf2 and cell competition. Using Drosophila we have shown that activation of the transcription factor Nrf2, a major regulator of the oxidative stress response, turns cells into losers that are killed by surrounding normal cells. Currently we are addressing how Nrf2 activity leads to cell competition.
- Cell competition and cancer. Following on our earlier work, we are using Drosophila intestinal tumour models to further investigate the mechanisms of tumour-host cell competition.
- Cell competition and human diseases. We are currently establishing cell-based models of human diseases, using human primary cells to investigate if/how cell competition might contribute to some genetic diseases.
Our lab is generously funded by the Wellcome Trust and by CRUK, as Eugenia is the recipient of a Wellcome Trust Senior Research Fellowship and of a CRUK Programme Foundation Award.
Qualifications and History
- 2001: PhD European Molecular Biology Laboratory, Heidelberg, Germany
- 2002-2009: Post-doc, National Institute for Medical Research, London, UK
- 2010-2017: Group leader, The Gurdon Institute, University of Cambridge
- 2016-2017: Senior Research Fellow, University of Bristol
- 2017 - : Professorial Research Fellow in Cell Biology, University of Bristol
- 2002-2003: Marie-Curie Post-doctoral Fellow
- 2003-2005: EMBO Post-doctoral Fellow
- 2010-2017: Royal Society University Research Fellow
- 2017-2022: Wellcome Trust Senior Research Fellow
Find further publications in Explore Bristol Research
- Kucinski I#, Dinan M#, Kolahgar G, and Piddini E. Chronic activation of JNK, JAK/STAT and oxidative stress signalling causes the loser cell status. Nature Comm. 2017 Jul 26;8(1):136. doi: 10.1038/s41467-017-00145-y
- Balasooriya GI, Goschorska M, Piddini E and Rawlins EL. FGFR2 is required for airway basal cell self-renewal via SOX2 maintenance. Development. 2017 May 1;144(9):1600-1606. doi: 10.1242/dev.135681.
- Wagstaff L, Goschorska M, Kozyrska K, Duclos G, Kucinski I, Chessel A, Hampton-O’Neil L, Bradshaw CR, Allen GE, Rawlins EL, Silberzan P, Carazo Salas RE and Piddini E. Mechanical cell competition kills cells via induction of lethal p53 levels. Nature Comm. 2016, 7, 11373
- Suijkerbuijk SJE, Kolahgar G, Kucinski I, Piddini E. Cell competition drives the growth of intestinal adenomas in Drosophila. Curr. Biol. 2016 Feb 22;26(4):428-38. Recommended by the Faculty of 1000
- Kolahgar G, Suijkerbuijk SJE, Poirier E, MansourS, Simons BD and Piddini, E. Cell competition modifies adult stem cell and tissue population dynamics in a JAK-STAT dependent manner. Dev. Cell. 2015 Aug 10;34(3):297-309 Featured Article. Recommended by the Faculty of 1000