Maria Alcolea’s laboratory focusses on understanding the behaviour of epithelial stem and progenitor cells in health and disease. 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. Combining genetic lineage tracing approaches with a novel 3D oesophageal organ culture system, Maria’s work has revealed the remarkable fate plasticity of the oesophageal epithelium. Her work has shown how cells are not only able to rewire their programme of cell behaviour in response to developmental cues, injury and early tumour formation, but has also demonstrated their ability to switch their identity well beyond physiological constraints under the right environmental cues. Investigating the cellular and molecular mechanisms governing this dynamic cell behaviour, and the potential implications for early cancer development represent Maria’s main interests.
A few recent papers:
Bejar MT, Jimenez-Gomez P, Moutsopoulos I, Ajith H, Colom B, McGinn J, Han S, Skrupskelyte G, Calero-Nieto FJ, Göttgens B, Mohorianu II, Simons BD, Alcolea MP. Lifting regenerative barriers promotes epithelial cell fate plasticity supporting lineage conversion.Nat Commun. 2025 Nov 27;16(1):11305. doi: 10.1038/s41467-025-66446-9.
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, King C, 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 Oct;56(10):2158-2173. doi: 10.1038/s41588-024-01875-8. Epub 2024 Sep 23.
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. doi: 10.1158/2159-8290.CD-24-0097.
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 oesophageal epithelium. Nat Cell Biol. 2021 May;23(5):511-525. doi: 10.1038/s41556-021-00679-w. Epub 2021 May 10.
