Alcolea Group

Dr Maria Alcolea

Epithelial cell fate and plasticity

Email: mpa28@cam.ac.uk     |     Departmental Affiliation: Oncology

Research

Plain English: Epithelial cells have the essential role of protecting us from external aggressions. However, this critical barrier must be able to adapt in order to face changes during developmental tissue formation and wound healing. A cut in our skin activates a number of cellular responses ensuring that the breach is fixed in few days, recovering the protective barrier. However, given that development and wound healing require the production of a significant amount of new tissue in a relatively short time, it is not surprising that cancer cells mimic these processes to rapidly produce a tumour mass. The difference being that tissue formation and wound repair are very controlled processes, while cancer is not. The Alcolea Group aims to investigate these adaptive cellular responses and the molecular mechanisms behind them in order to understand epithelial tissue behaviour, and how this can go awry during cancer development.

Research Focus: The Alcolea Group research interests have been focused on studying the behaviour of progenitor cells in the mouse oesophagus as a model to unveil the basic rules underlying squamous epithelial cell fate. Their work in the field has revealed how this tissue is maintained under homeostatic conditions, and how these rules switch upon injury.

More recently they have been able to identify how progenitor cells alter and adapt their behaviour in response to preneoplastic mutations, reflecting their remarkable cellular plasticity. Investigating the cellular and molecular mechanisms governing this dynamic behaviour and the potential implications for early cancer development will constitute the basis of my research programme.

To answer these questions, the group plans to make use of a combination of in vivo lineage tracing techniques, transcriptional network analysis, as well as 3D organoid and explant culture systems.　

The study of stem cell dynamics by combining fate mapping, live-imaging, and single-cell molecular profiling of in vivo and 3D in vitro epithelial systems with the aim to improve regeneration, prevent cancer formation and ageing.

Alcolea Group photo 

Key publications

• Skrupskelyte G*, Rojo Arias JE*, Dang Y, Han S, Bejar MT, Colom B, Fowler JC, Jones PH, Rulands S, Simons BD, Alcolea MP. Pre-cancerous Niche Remodelling Dictates Nascent Tumour Survival. PREPRINT bioRxiv 2024.07.04.602022
• Herms A*, Fernandez-Antoran D*, Alcolea MP*, Kalogeropoulou A, Banerjee U, Piedrafita G, Abby E, Valverde-Lopez JA, Ferreira IS, Caseda I, Bejar MT, Dentro SC, Vidal-Notari S, Ong SH, Colom B, Murai K, KingC, Mahbubani K, Saeb-Parsy K, Lowe AR,  Gerstung M,  Jones PH. Self-sustaining long-term 3D epithelioid cultures reveal drivers of clonal expansion in esophageal epithelium. Nat Genet. 2024 Sep; 56, 2158–2173
• Alcolea MP, Alonso-Curbelo D, Ambrogio C, Bullman S, Correia AL, Ernst A, Halbrook CJ, Kelly GL, Lund AW, Quail DF, Ruscetti M, Shema E, Stromnes IM, Tam WL. Cancer Hallmarks: Piecing the Puzzle Together. Cancer Discov. 2024 Apr 4;14(4):674-682
• Colom B, Herms A, Hall MWJ, Dentro SC, King C, Sood RK, Alcolea MP, Piedrafita G, Fernandez-Antoran D, Ong SH, Fowler JC, Mahbubani KT, Saeb-Parsy K, Gerstung M, Hall BA, Jones PH. Mutant clones in normal epithelium outcompete and eliminate emerging tumours. Nature. 2021 Oct;598(7881):510-514.
• Bejar MT*, Jimenez-Gomez P*, Moutsopoulos I, Colom B, Han S, Calero-Nieto FJ, Göttgens B, Mohorianu I, Simons BD, Alcolea MP. Defining the transcriptional signature of esophageal-to-skin lineage conversion. PREPRINT, bioRxiv. 2021, 431899
• McGinn J, Hallou A, Han S, Krizic K, Ulyanchenko S, Iglesias-Bartolome R, England FJ, Verstreken C, Chalut KJ, Jensen KB, Simons BD, Alcolea MP. A biomechanical switch regulates the transition towards homeostasis in esophageal epithelium. Nat Cell Biol. 2021 May;23(5):511-525.
• Colom B, Alcolea MP, Piedrafita G, et al. Spatial competition shapes the dynamic mutational landscape of normal esophageal epithelium. Nat Genet. 2020 Jun;52(6):604-614
• Alcolea MP, Greulich P, Wabik A, Frede J, Simons BD, Jones PH. Differentiation imbalance in single Oesophageal progenitor cells causes clonal immortalization and field change. Nat Cell Biol. 2014 Jun;16(6):615-22
• Doupé DP*, Alcolea MP*, Roshan A, Zhang G, Klein AM, Simons BD, Jones PH. A Single Progenitor Population Switches Behavior to Mainta in and Repair Esophageal Epithelium. Science. 2012 Aug 31;337(6098):1091-3.