Claudia Barros Lab – Neural Stem Cells and Brain Tumourigenesis Research

Research focus: Neural stem cell regulation in health and brain tumour development

Image shows Neural Stem Cells (green, GFP) inside the Drosophila brain, some about to divide (red, CyclinB). Courtesy of Claudia Barros Lab

Postnatal neurogenesis promotes brain plasticity and function. Intrinsic and extrinsic signals converge to promote appropriate postembryonic NSC development and maintenance. Restricting NSC potential is equally vital as the expansion of aberrant neural stem-like cells can lead to brain tumour growth.

Our main goal is to identify fundamental intrinsic Neural Stem Cell (NSC) properties and extrinsic niche signals regulating the pace of postembryonic neurogenesis in both health and in disease, such as upon neoplastic transformation. We use a well-known genetically tractable in vivo model – the fruit fly Drosophila brain – and translate findings into mammalian systems, as well as human brain samples.

Current projects in the laboratory address three major questions in NSC biology:

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Courtesy of Claudia Barros Lab

Q1: How do NSCs transit from a quiescent to a mitotically active state?

As in mammals, Drosophila postembryonic NSCs transit from quiescence to a mitotically active state to generate adult brain neurons and glia. The mechanisms underlying NSC mitotic reactivation remain largely unknown. We are screening and characterising the role of genes involved in this process using Drosophila, and aim at investigating conserved functions in mammalian systems.

Q2: How is the identity of different NSCs established?

It is becoming increasingly clear that the developing and adult mammalian brain harbours distinct NSC types. Yet, information about their molecular identity is currently at its infancy. The identification of different NSC types in the Drosophila larval brain, the evolutionary conservation of regulatory mechanisms, and the genetic tools available prompted us to use Drosophila as a model to identify novel NSC type-specific molecular properties that may be conserved in mammals.

Q3: What are the key mechanisms responsible for the transformation of normal NSC lineage cells into brain tumour-initiation cells?

Cells with NSC-like characteristics exist within brain tumours and can reform whole tumour masses. These so-called brain cancer stem cells are thought to originate from de-differentiation and/or transformation of normal NSC lineage cells. Using a Drosophila brain tumour model, we are screening and characterising genes potentially involved in molecular changes leading to brain tumour initiation and growth. We translate our findings into mammalian systems, including patient-derived brain cancer stem cells and human brain tumour tissues.

Prospective students or staff interested in joining our group, please contact Dr Claudia Barros .

Current lab members

Dr Claudia Barros

Associate Professor of Neuroscience/ Principal Investigator

claudia.barros@plymouth.ac.uk

Dr Jon Gil-Ranedo

Research Fellow in Cancer Stem Cell Neurobiology

jon.gil-ranedo@plymouth.ac.uk

Ella Harris

ResM student

Rosie Moore

PhD student

Sarah Robbins

PhD student

A main focus of our team is to understand how brain tumours form. That is the initial events transforming normal cells into brain tumour initiating cells and their development.

Dr Claudia Barros
Associate Professor of Neuroscience (Research)

Watch Dr Claudia Barros discuss the work of the team on YouTube

Plymouth Brain Tumour Research Centre of Excellence

Our team is part of the Plymouth Brain Tumour Research Centre of Excellence sponsored by Brain Tumour Research.

Watch Dr Jon Gil Ranedo talk about the work of the group on YouTube

Plymouth Brain Tumour Research Centre of Excellence Wall of Hope, courtesy of Claudia Barros Lab

Lab celebrations

Feb 2024: View our new publication Ribogenesis boosts controlled by HEATR1-MYC interplay promote transition into brain tumour growth
Jan 2024: Congratulations to Nsikan Nsek for his PhD viva.
July 2023: Congratulations to Jamie Pugh for his PhD degree.
July 2021: Check our publication in collaboration with Dr Torsten Bossing on TNF signalling and mitotic entry following damage in the brain.
January 2021: Congratulations to Laura Rodriguez Diaz for her PhD viva.
January 2020: Congratulation to Eleanor Gonzaga for defending her PhD thesis.
June 2019: Check out our publication on Neural Stem Cell reactivation.
September 2017: Research to explore the development of deadly brain tumours.
July 2017: The Navy And Neuroscience: Reservist Joins Stem Cell Research Team.
June 2017: Congratulations to Laura Rodriguez-Diaz for her third-place prize at the Plymouth three-minute PhD Thesis competition.

April 2017: Congratulations to Laura Rodriguez-Diaz for her first-place poster prize at the Annual Plymouth PSMD postgraduate research conference.
October 2016: Congratulations to Karolina Jaworek for her PhD degree.
October 2014: Funding for better understanding of neural stem cells.

Image shows neural stem cell lineages (green) in the Drosophila brain

Alumni and next destinations:

Jamie Pugh (PhD, 2023), Medical Writer, Oxford PharmaGenesis
Nsikan Nsek (PhD viva 2024), postdoctoral researcher, MRC Laboratory of Medical Sciences, London, UK
Laura Rodriguez Diaz (PhD 2016–20), Scientist, Theolytics Biotech, Oxford, UK
Eleanor Gonzaga (PhD 2013–16, 2018–19), Postdoctoral Research Associate, University of Cambridge, UK
Karolina Jaworek (PhD 2012–16), Postdoctoral Research Associate, University of Exeter, UK

Annabelle Mufti (2023-24), Paula Varney (2017–18), Joao Marques (2015–16), Eleni Costa (2015–16) and Oliver Warrington (2014–15) – one-year research undergraduates
Matthew Sherwood (Postgraduate research placement, May–September 2017), PhD student, University of Southampton, UK
Eleanor Gonzaga (MRes 2013–14, PhD University of Plymouth) and Helena Robinson (MRes 2013–14, PhD Bangor University UK)
Thomas Hughes (2015), Joshua Lewis (2016) and Chelsey Wiley (2017) – MSc students
Hubert Bieluczyk (Research Assistant, February–September 2018), Data Scientist, Legal & General, UK

Claudia Barros Lab image gallery

Images courtesy of Claudia Barros Lab

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Claudia Barros Lab - Neural Stem Cell Research

Neural Stem Cells (green) in the early Drosophila larval brain

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Neural Stem Cells (green) in the late Drosophila larval brain

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Neural Stem Cells dividing (blue) in the Drosophila ventral nerve cord

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Neurons in the mouse brain cortex

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Mouse hippocampal neuron in culture

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Purkinge cells in the mouse cerebellum

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Neural Stem Cells (pink) in the early Drosophila larval brain

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Neural Stem Cells (green) in the Drosophila brain lobe

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Brain tumoursphere

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Cancer (Glioma) Stem Cells differentiating in culture

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Publications

Diaz LR, Gil-Ranedo J, Jaworek KJ, Nsek N, Marques JP, Costa E, Hilton DA, Bieluczyk H, Warrington O, Hanemann CO, Futschik ME, Bossing T & Barros CS (2024). Ribogenesis boosts controlled by HEATR1-MYC interplay promote transition into brain tumour growth. EMBO Reports Jan;25(1):168-197, DOI PEARL
Barros CS & Bossing T (2021) 'Microtubule disruption upon CNS damage triggers mitotic entry via TNF signaling activation' Cell Reports 36, (1), DOI Open access
Gil-Ranedo J, Gonzaga E, Jaworek KJ, Berger C, Bossing T & Barros CS (2019) 'STRIPAK Members Orchestrate Hippo and Insulin Receptor Signaling to Promote Neural Stem Cell Reactivation' Cell Reports 27, (10) 2921-2933.e5, DOI PEARL
Raghu SV, Mohammad F, Chua JY, Lam JSW, Loberas M, Sahani S, Barros CS & Claridge-Chang A 2018 'A zinc-finger fusion protein refines Gal4-defined neural circuits' Molecular Brain 11, (1) 46-46 Author Site, DOI PEARL
Xu J, Hartley BJ, Kurup P, Phillips A, Topol A, Xu M, Ononenyi C, Foscue E, Ho S-M & Baguley TD 2016 'Inhibition of STEP61 ameliorates deficits in mouse and hiPSC-based schizophrenia models' Molecular Psychiatry, DOI PEARL
Ding R, Weynans K, Bossing T, Barros CS & Berger C 2016 'The Hippo signalling pathway maintains quiescence in Drosophila neural stem cells' Nature Communications 7, 10510-10510, DOI PEARL
Cahill ME, Jones KA, Rafalovich I, Xie Z, Barros CS, Müller U & Penzes P 2012 'Control of interneuron dendritic growth through NRG1/erbB4-mediated kalirin-7 disinhibition' Mol Psychiatry 17, (1) 1-107 Author Site, DOI PEARL

Bossing T, Barros CS, Fischer B, Russell S & Shepherd D 2012 'Disruption of microtubule integrity initiates mitosis during CNS repair' Dev Cell 23, (2) 433-440 Author Site, DOI PEARL
Barros CS, Franco SJ & Müller U 2011 'Extracellular matrix: functions in the nervous system' Cold Spring Harb Perspect Biol 3, (1) Author Site, DOI PEARL
Barros CS, Nguyen T, Spencer KSR, Nishiyama A, Colognato H & Müller U 2009 'Beta1 integrins are required for normal CNS myelination and promote AKT-dependent myelin outgrowth' Development 136, (16) 2717-2724 Author Site, DOI PEARL
Barros CS, Calabrese B, Chamero P, Roberts AJ, Korzus E, Lloyd K, Stowers L, Mayford M, Halpain S & Müller U 2009 'Impaired maturation of dendritic spines without disorganization of cortical cell layers in mice lacking NRG1/ErbB signaling in the central nervous system' Proc Natl Acad Sci U S A 106, (11) 4507-4512 Author Site, DOI PEARL
Radakovits R, Barros CS, Belvindrah R, Patton B & Müller U 2009 'Regulation of radial glial survival by signals from the meninges' J Neurosci 29, (24) 7694-7705 Author Site, DOI PEARL
Barros CS, Phelps CB & Brand AH 2003 'Drosophila nonmuscle myosin II promotes the asymmetric segregation of cell fate determinants by cortical exclusion rather than active transport' Dev Cell 5, (6) 829-840 Author Site PEARL
Bossing T, Barros CS & Brand AH 2002 'Rapid tissue-specific expression assay in living embryos' Genesis 34, (1-2) 123-126 Author Site, DOI PEARL
Van Roessel P, Hayward NM, Barros CS & Brand AH 2002 'Two-color GFP imaging demonstrates cell-autonomy of GAL4-driven RNA interference indrosophila' genesis 34, (1-2) 170-173, DOI PEARL