Dr Maria Alcolea
Epithelial cell fate and plasticity
Laboratory: Cambridge Stem Cell Institute, Gleeson Building.
Departmental Affiliation: Oncology
In 2007 Maria received her PhD in Biochemistry at the University of the Balearic Islands, Spain. She then moved to Barts Cancer Institute - Queen Mary University of London to start her Postdoctoral training with Dr. P.R. Cutillas, where she used phosphoproteomic approaches to study cancer drug resistance. In 2009 she joined Prof Phil Jones laboratory at the Hutchison/MRC cancer unit where she was awarded a Marie Curie Intra-European Fellowship (FP7). There she spent a total of 6 years studying epithelial stem cell behaviour using genetic lineage tracing approaches and methods from statistical physics.
In 2015, Maria was awarded a Wellcome/The Royal Society Sir Henry Dale Fellowship to establish her own laboratory to study epithelial stem cell plasticity in response to injury and tumour development.
Maria is currently a Principal Investigator at the Wellcome Trust/MRC Cambridge Stem Cell Institute and affiliate to the Oncology Department, University of Cambridge.
Wellcome, Royal Society, Isaac Newton Trust, Cancer Research UK Cambridge Centre
Oesophageal progenitors (yellow cells) redefine their behaviour in response to injury. White label indicates cells recruited to proliferation (Science 2012, 31;337(6098):1091-3).
My 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. My work in the field has revealed how this tissue is maintained under homeostatic conditions, and how these rules switch upon injury.
More recently I 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, I will make use of a combination of in vivo lineage tracing techniques, transcriptional network analysis, as well as 3D organoid and explant culture systems.
Anne-Lore Bex, Paula Jimenez Gomez, Jamie McGinn
For people interested in joining my lab, please contact me directly (firstname.lastname@example.org)
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. My proposed research 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.
- 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. PMCID:PMC4085550
- Casado P, Alcolea MP, Iorio F, Rodríguez-Prados JC, Vanhaesebroeck B, Saez-Rodriguez J, Joel S, Cutillas PR. Phosphoproteomics data classify hematological cancer cell lines according to tumor type and sensitivity to kinase inhibitors. Genome Biol. 2013 Apr 29;14(4):R37. PMCID:PMC4054101
- Alcolea MP, Jones PH. Tracking cells in their native habitat: lineage tracing in epithelial neoplasia. Nat Rev Cancer. 2013 Mar;13(3):161-71. PMID:23388619
- Doupé DP*, Alcolea MP*, Roshan A, Zhang G, Klein AM, Simons BD, Jones PH. (2012) A Single Progenitor Population Switches Behavior to Maintain and Repair Esophageal Epithelium. Science. 2012 Aug 31;337(6098):1091-3. *Equal contribution. PMCID:PMC3527005
- Alcolea MP, Casado P, Rodríguez-Prados JC, Vanhaesebroeck B, Cutillas PR. (2012) Phosphoproteomic Analysis of Leukemia Cells under Basal and Drug-treated Conditions Identifies Markers of Kinase Pathway Activation and Mechanisms of Resistance. Mol Cell Proteomics. 11(8), 453-66. PMCID:PMC3412974