Silvia Marino

Title: Professor
MD, FMH-Path, EFPath, FRCPath
Professor of Neuropathology

The focus of the Marino research group is on the biology of stem cells and progenitor cells, on the pathways and genes involved in control of their maintenance, proliferation and differentiation, in particular the Polycomb group genes. We have developed a collection of genetically engineered mouse models and cellular assays derived thereof to study signalling mechanisms and transcriptional programme regulating self-renewal of stem cells. We are particularly interested in assessing how fine tuning of the expression of these genes can be exploited to enhance the regenerative function of stem cells in ageing and disease. We currently work with two model systems, the brain and the skeletal muscle.

Moreover we are investigating the role of deregulated self-renewal mechanisms in initiation and progression of brain tumours –medulloblastomas and glioblastomas- in experimental models and in human tumour samples.

 

Bio

Silvia Marino is Professor of Neuropathology at Barts and The London School of Medicine and Dentistry, Queen Mary University of London and also Honorary Consultant Neuropathologist at Barts Health NHS Trust. After studying Medicine at the University of Turin in Italy, Professor Marino trained in Neuropathology and Histopathology at the University of Zurich in Switzerland. She trained in molecular genetics with Professor Anton Berns at The Netherlands Cancer Institute in Amsterdam as a Marie Curie Postdoctoral Fellow of the European Community studying the role of the tumour suppressor Rb and p53 in the pathogenesis of medulloblastoma in genetically engineered mouse models. She established her own laboratory research group in 2002 firstly at the Institute of Pathology, University of Zurich and then since 2006 at the Blizard Institute in London.

Research

Research

We study epigenetic mechanisms regulating the biology of normal and neoplastic stem cells. We are investigating the role of deregulated self-renewal mechanisms in initiation and progression of brain tumours. Moreover, we are interested in assessing how fine tuning of the expression of chromatin modifiers, such as PcG genes, can be exploited to enhance the regenerative function of stem cells in developmental and adult diseases.

Brain Tumour Research Centre of Excellence

The research will focus on glioblastoma multiforme (GBM), the most common and most aggressive malignant brain tumour of adulthood. The aim of the research is to increase our understanding of the cells within the brain from which GBM originates. The team will look at how this particular type of brain tumour develops from normal cells, and which genes and biological functions control its behaviour. By uncovering this essential knowledge, the clinical evaluation of each individual patient can be improved and better and more specific drugs which target the tumour cells can be identified.

Polycomb group genes and satellite cells in skeletal muscle regeneration

Adult skeletal muscle has a remarkable ability to repair itself after injury as a result of its resident stem cell population, the ‘satellite cells’. We are studying the impact of loss and gain of the PcG gene Bmi1 on the regenerative capacity of the satellite cells.

Mouse models of medulloblastoma.

Novel signalling pathways involved in the metastatic spread of these highly aggressive brain tumours of childhood are being investigated.

 

Current projects in the lab are funded by the MRC, Brain Tumour Research, Barts and The London Charity and NIHR.

Group Members

Academic staff
Prof Silvia Marino (Group Lead)

Dr Maria Niklison-Chirou (Children with Cancer UK Fellow)

Post-Doctoral Researchers and Fellows

Dr Claire Vinel, Dr Loredana Guglielmi, Dr Sara Badodi, Dr Gabriel Rosser,

Clinical Research Fellows
Dr Ashirward Merve, Dr Tom Millner

PhD Researchers
Ms Barbara Ricci, Mr James Boot

Research Technician
Dr Xinyu Zhang

Administrative staff
Ms Jayanthi Rajamanje (Centre Manager)

Mr Alan Flynn (NIHR IAT Programme Administrator)

Publications

Original Research Articles

V Di Foggia, X Zhang, D Licastro, M F M Gerli, R Phadke, F Muntoni, P Mourikis, S Tajbakhsh, M Ellis, L C Greaves, R W Taylor, G Cossu, L G Robson and S Marino. Bmi1 enhances skeletal muscle regeneration through MT1 mediated oxidative stress protection in a mouse model of dystrophinopathy. J Exp Med. 2014 Dec 15;211(13):2617-33

A Merve, AM Dubuc, X Zhang, M Remke, PA Baxter, XN Li, MD Taylor, S Marino. Polycomb group gene BMI1 controls invasion of medulloblastoma cells and inhibits BMP-regulated cell adhesion. Acta Neuropathol Commun. 2014 Jan 24;2(1):10. doi: 10.1186/2051-5960-2-10.

S Acquati, A Greco, D Licastro, H Bhagat, D Ceric, Z Rossini, J Grieve, M Shaked-Rabi, N V Henriquez, S Brandner, E Stupka and S Marino. Epigenetic regulation of Survivin by Bmi1 is cell type specific during corticogenesis and in gliomas. Stem Cells 2013 Jan 31(1):190-202

H Behesti, H Bhagat, A Dubuc, M Taylor and S Marino. Bmi1 overexpression in the cerebellar granule cell lineage affects cell proliferation and survival without initiating medulloblastoma formation. Dis Model Mech 2013 Jan;6(1):49-63

LG Robson, V Di Foggia, A Radunovic, K Bird, X Zhang and S Marino. Bmi1 is expressed in postnatal myogenic satellite cells, controls their maintenance and plays an essential role in repeated muscle regeneration. PLoS One. 2011;6(11):e27116. Epub 2011 Nov 9.

DD Ateh, VH Leinster, SR Lambert, A Shah, A Khan, HJ Walklin, JV Johnstone, NI Ibrahim, MM Kadam, Z Malik, M Gironès, GJ Veldhuis, G Warnes, S Marino, IA McNeish, JE Martin. The intracellular uptake of CD95 modified paclitaxel-loaded poly(lactic-co-glycolic acid) microparticles. Biomaterials. 2011 Nov;32(33):8538-47. Epub 2011 Aug 6.

Zhang, A. Santuccione, C. Leung and S. Marino. Differentiation of postnatal cerebellar glial progenitors is controlled by Bmi1 through BMP pathway inhibition. Glia. 2011 Jul;59(7):1118-31. doi: 10.1002/glia.21184. Epub 2011 May 4

Yadirgi, V. Leinster, S. Acquati, H. Bhagat, O. Shakhova and S. Marino. Conditional activation of Bmi1 expression regulates self-renewal, apoptosis and differentiation of neural stem/progenitor cells in vitro and in vivo. Stem Cells. 2011 Apr 29(4):700-12

Subkhankulova, X. Zhang, C. Leung and S. Marino. Bmi1 directly represses p21Waf1/Cip1 in Shh-induced proliferation of cerebellar granule cell progenitors. Mol Cell Neurosci. 2010 Oct;45(2):151-62. Epub 2010 Jun 20.

Sutter, O. Shakhova, C. Sutter, S. Penkar, H. Bhagat, A. Santuccione, R. Bernays, F. L. Heppner, U. Schüller, M. Grotzer, H. Moch, P. Schraml and S. Marino. Cerebellar stem cells act as medulloblastoma initiating cells in a mouse model and a neural stem cell signature characterises a subset of human medulloblastoma. Oncogene 2010 Mar 25;29(12):1845-56.

Shakhova, C. Leung, E. van Montfort, A. Berns and S. Marino. Lack of Rb and p53 delays cerebellar development and predisposes to large cell anaplastic medulloblastzomas through amplification of N-Myc and Ptc2. Cancer Research 2006; 66 5190-5200

Bruggeman, M. Lingbeek, P. van der Stoop, J. Jacobs, K. Kieboom, E. Tanger, D. Hulsman, C. Leung, S. Marino and M. van Lohuizen. Ink4a and Arf differentially affect cell proliferation and neural stem cell self-renewal in Bmi1 deficient mice. Genes & Development 2005; 19:1438-1443

Leung, M. Lingbeek, O. Shakhova, J. Liu, E. Tanger, P. Saremaslani, M. van Lohuizen, S. Marino. Bmi1 is essential for cerebellar development and is overexpressed in human medulloblastomas. Nature 2004; 428(6980):337-41


View all Silvia Marino's Research Publications at: http://www.researchpublications.qmul.ac.uk

Teaching

Undergraduate

MBBS
BDS
BSc Neuroscience (Intercalated)
BSc Experimental Medicine (Intercalated)

Postgraduate

MSc Neuroscience and Translational Medicine
MSc Regenerative Medicine
MSc Molecular Pathology of Tumours (BCI)

Prof Marino is the lead for the NIHR Integrated Academic Clinical Training at QMUL
 
PhD Studentships

Prof Marino is pleased to consider applications from prospective PhD students.

 

Professional development

 

Lab experience placements

Prof Marino is pleased to consider applications for prospective lab placements.

 


Further information

  • Vice-President of the British Neuro-Oncology Society (BNOS) past honorary secretary to the society
  • Chair of the academic committee of the British Neuropathology Society (BNS) since 2015
  • Member of the scientific advisory board of Children with Cancer UK
  • Member of the scientific advisory board of Brain Tumour Research
  • Member of the NCRI Clinical Studies Group in Brain Tumours since August 2014
  • Member of the academic committee of the European Association of Neuro-Oncology since October 2014
  • Member of the Editorial Board Neuropathology and Applied Neurobiology
  • Organizer of the Glioma Club since 2010

Contact

Centre for Genomics and Child Health

Blizard Institute

Barts and The London School of Medicine and Dentistry

4 Newark Street

London E1 2AT

Prof. Silvia Marino - Email: This email address is being protected from spambots. You need JavaScript enabled to view it. Tel: +44 (0) 20 7882 2585, Fax: +44 (0) 20 7882 2180

Dr Xinyu Zhang - Email: This email address is being protected from spambots. You need JavaScript enabled to view it. Tel: +44 (0) 20 7882 2201, Fax: +44 (0) 20 7882 2180

Mr Alan Flynn - Email: This email address is being protected from spambots. You need JavaScript enabled to view it. Tel: +44 (0) 20 7882 3365

 

 

Centre Manager: Jaya Rajamanie, 020 7882 2619 (This email address is being protected from spambots. You need JavaScript enabled to view it.)

Centre Administrators: Shirley Dankyi-Larbi, 0207 882 2615 (This email address is being protected from spambots. You need JavaScript enabled to view it.), Julia Moreta-Diaz, 0207 882 2618 (This email address is being protected from spambots. You need JavaScript enabled to view it.)