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Prof Sebastian Brandner

Summary

I started my research career during Medical School in Göttingen, at the Max Planck Institute of Biophysical Chemistry with Professor Creutzfeldt, where I studied the projection of the thalamocortical auditory system in the cat, resulting in several research publications as first author. 

During my postgraduate training in Neuropathology, I joined the Institute of Neuropathology in Zurich, where I started my research on prion disease, resulting in seminal publications in Nature and PNAS. 

After qualifying as a Consultant Neuropathologist in 1998, I established my own research group and developed mouse models to study neural development and brain tumours. In 2001, I was recruited through the MRC international recruitment scheme to join the MRC Prion Unit at UCL Institute of Neurology. 

In 2004 I was appointed as Chair of Neuropathology and Head of the Division of Neuropathology at Queen Square, one of the largest academic neuropathology departments in the UK.

At the MRC Prion Unit and the Institute of Neurology I integrated clinical neuropathology with experimental models on neurodegenerative diseases including prion diseases, which still remain a strong focus in my highly collaborative research. I am an expert on the pathology of both human and experimental models of prion disease worldwide and I maintains a close collaboration with the MRC Prion Unit and the National Prion Clinic at the National Hospital, Queen Square. 

I recently conducted a study “prevalence screening for the presence of vCJD prions” for the HPA, which has major implications for UK policy. At the Institute of Neurology, I also expanded my research on brain tumours which resulted in a number of excellent publications in Development and EMBO Journal. I developed a strong team working on brain cancer, and established close collaborations between UCL Cancer Centre and the Brain Tumour Unit at the National Hospital. I contribute nationally to brain cancer research in my role as council member of the British Neuro-oncology Society. Academic pathology and research on experimental models and their translation to human diseases are recognised key development areas in the UK. 











Research Summary

Modelling intrinsic brain tumours: Oncogenic signalling in neural stem cells

Intrinsic benign and malignant brain tumours, such as astrocytomas and glioblastoma are thought to originate from a population of stem cells in the adult brain. Stem cells divide in the adult brain to form more mature cells such as nerve cells (neurones) astrocytes (supporting cells) or oligodendrocytes (myelin forming cells that wrap processes of neurones in the white matter). We are working on the mechanisms of how mutations in genes that control cell division and migration of stem cells can cause brain tumours.

A novel aspect of our work is that the type of tumours depends on the pattern of mutations in stem cells, even when mutated stem cells are taken away from their normal environment and are placed in other areas of the brain. Knowledge of this mechanism is an important step towards the understanding where brain tumours originate from and how a certain type of brain tumour forms. 

How does the model work?

We inactivate tumour suppressor genes (PTEN, RB, p53) in the neural stem cell compartment. By injecting Cre-expressing virus into the ventricles of conditional knockout mice (PTENlox/lox, p53lox/lox and Rblox/lox in various combinations) the targeted genes are recombined only in cells located near the sub-ventricular zone (SVZ) which contains the largest known population of neural stem cells. In mice where Rb and p53, or the trio of the genes, PTEN, P53 and Rb are recombined, after several months, tumours of a specific phenotype resembling that of a human PNET develop. Instead, a tumour resembling human glioma (similar to oligoastrocytomas) is induced in mice where PTEN and P53 are targeted

Several weeks to months prior to the development of large tumours, small neoplastic lesions can be observed which we call microneoplasia. The assumption is that during the considerable time it takes to develop evident tumours additional genetic lesions are accumulated on top of the ones induced by Cre-recombination 







Research Activities

  • Glial development in the PNS
  • Investigating the molecular basis of frontotemporal dementia
  • Neural stem cells and brain tumours
  • Neuropathology of Stem Cells in Children
  • Perinatal Neuroscience
  • The neurogenetics of neurodegenerative disease

Recent Publications

Displaying 50 most recent publications. For the full list please visit UCL Discovery

  1. Marquez-Infante C,Murphy SM,Mathew L,Alsanousi A,Lunn MP,Brandner S,Yousry TA,Blake J,Reilly MM (2013) Asymmetric sensory ganglionopathy: A case series Muscle and Nerve.
  2. Osellame LD,Rahim AA,Hargreaves IP,Gegg ME,Richard-Londt A,Brandner S,Waddington SN,Schapira AHV,Duchen MR (2013) Mitochondria and quality control defects in a mouse model of Gaucher disease - links to Parkinson’s Disease Cell Metabolism.
  3. Cottenie E,Menezes MP,Rossor AM,Morrow JM,Yousry TA,Dick DJ,Anderson JR,Jaunmuktane Z,Brandner S,Blake JC,Houlden H,Reilly MM (2013) Rapidly progressive asymmetrical weakness in Charcot-Marie-Tooth disease type 4J resembles chronic inflammatory demyelinating polyneuropathy. Neuromuscul Disord, 23(5), 399 - 403. 10.1016/j.nmd.2013.01.010.
  4. Acquati S,Greco A,Licastro D,Bhagat H,Ceric D,Rossini Z,Grieve J,Shaked-Rabi M,Henriquez NV,Brandner S,Stupka E,Marino S (2013) Epigenetic regulation of survivin by Bmi1 is cell type specific during corticogenesis and in gliomas. Stem Cells, 31(1), 190 - 202. 10.1002/stem.1274.
  5. Reiniger L,Mirabile I,Lukic A,Linehan J,Groves M,Rudge P,Collinge J,Mead S,Brandner S (2013) Filamentous white matter prion protein deposition is a distinctive feature of multiple inherited prion diseases NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 39, 23 - 24.
  6. Akhtar S,Grizenkova J,Wenborn A,Hummerich H,Fernandez de Marco M,Brandner S,Collinge J,Lloyd SE (2013) Sod1 deficiency reduces incubation time in mouse models of prion disease. PLoS One, 8(1), e54454. 10.1371/journal.pone.0054454.
  7. Galavotti S,Bartesaghi S,Faccenda D,Shaked-Rabi M,Sanzone S,McEvoy A,Dinsdale D,Condorelli F,Brandner S,Campanella M,Grose R,Jones C,Salomoni P (2013) The autophagy-associated factors DRAM1 and p62 regulate cell migration and invasion in glioblastoma stem cells. Oncogene, 32(6), 699 - 712. 10.1038/onc.2012.111.
  8. Watts C,Brandner S (2012) Emerging Concepts in Neuro-Oncology.
  9. Zadeh G,Salehi F,An S,Uff C,Camp S,Revesz T,Holton J,Thom M,McEvoy AW,Grieve J,Kitchen N,Brandner S (2012) Diagnostic implications of histological analysis of neurosurgical aspirate in addition to routine resections. Neuropathology, 32(1), 44 - 50. 10.1111/j.1440-1789.2011.01234.x.
  10. Hyare H,Ramlackhansingh A,Gelosa G,Edison P,Rudge P,Brandner S,Brooks DJ,Collinge J,Mead S (2012) 11C-PiB PET does not detect PrP-amyloid in prion disease patients including variant Creutzfeldt-Jakob disease. J Neurol Neurosurg Psychiatry, 83(3), 340 - 341. 10.1136/jnnp.2010.233692.
  11. Ghazi-Noori S,Froud KE,Mizielinska S,Powell C,Smidak M,Fernandez de Marco M,O'Malley C,Farmer M,Parkinson N,Fisher EM,Asante EA,Brandner S,Collinge J,Isaacs AM (2012) Progressive neuronal inclusion formation and axonal degeneration in CHMP2B mutant transgenic mice. Brain, 135(Pt 3), 819 - 832. 10.1093/brain/aws006.
  12. Davidson G,Murphy S,Polke J,Laura M,Salih M,Muntoni F,Blake J,Brandner S,Davies N,Horvath R,Price S,Donaghy M,Roberts M,Foulds N,Ramdharry G,Soler D,Lunn M,Manji H,Davis M,Houlden H,Reilly M (2012) Frequency of mutations in the genes associated with hereditary sensory and autonomic neuropathy in a UK cohort. J Neurol, 259(8), 1673 - 1685. 10.1007/s00415-011-6397-y.
  13. Murphy SM,Davidson GL,Brandner S,Houlden H,Reilly MM (2012) Mutation in FAM134B causing severe hereditary sensory neuropathy. J Neurol Neurosurg Psychiatry, 83(1), 119 - 120. 10.1136/jnnp.2010.228965.
  14. Weis J,Brandner S,Lammens M,Sommer C,Vallat JM (2012) Processing of nerve biopsies: a practical guide for neuropathologists. Clin Neuropathol, 31(1), 7 - 23.
  15. Grizenkova J,Akhtar S,Hummerich H,Tomlinson A,Asante E,Wenborn A,Fizet J,Poulter M,Wiseman F,Fisher EMC,Tybulewicz V,Brandner S,Colllinge J,Lloyd S (2012) Over-expression of Hspa13 (Stch) reduces prion disease incubation time in mice Proc Natl Acad Sci U S A, 09(34):13722-7. Epub 2012 Aug 6.
  16. Jaffer F,Murphy SM,Scoto M,Healy E,Rossor AM,Brandner S,Phadke R,Selcen D,Jungbluth H,Muntoni F,Reilly MM (2012) BAG3 mutations: another cause of giant axonal neuropathy. J Peripher Nerv Syst, 17(2), 210 - 216. 10.1111/j.1529-8027.2012.00409.x.
  17. Hyare H,Ramlackhansingh A,Gelosa G,Edison P,Rudge P,Brandner S,Brooks DJ,Collinge J,Mead S (2012) C-11-PiB PET does not detect PrP-amyloid in prion disease patients including variant Creutzfeldt-Jakob disease JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 83(3), 340 - 341.
  18. Kloehn P,Castro-Seoane R,Hummerich H,Sweeting T,Tattum H,Linehan J,de Marco MF,Brandner S,Collinge J (2012) Plasmacytoid dendritic cells sequester high prion titers at early stages of prion infection PRION, 6, 7 - 7.
  19. Castro-Seoane R,Hummerich H,Sweeting T,Tattum MH,Linehan JM,Fernandez de Marco M,Brandner S,Collinge J,Klöhn PC (2012) Plasmacytoid dendritic cells sequester high prion titres at early stages of prion infection. PLoS Pathog, 8(2), e1002538. 10.1371/journal.ppat.1002538.
  20. Klöhn PC,Farmer M,Linehan JM,O'Malley C,Fernandez de Marco M,Taylor W,Farrow M,Khalili-Shirazi A,Brandner S,Collinge J (2012) PrP antibodies do not trigger mouse hippocampal neuron apoptosis. Science, 335(6064), 52. 10.1126/science.1215579.
  21. Sheppard O,Plattner F,Rubin A,Slender A,Linehan JM,Brandner S,Tybulewicz VL,Fisher EM,Wiseman FK (2012) Altered regulation of tau phosphorylation in a mouse model of down syndrome aging. Neurobiol Aging, 33(4), 828.e31 - 828.e44. 10.1016/j.neurobiolaging.2011.06.025.
  22. Murphy SM,Davidson GL,Laura M,Salih MAM,Muntoni F,Lunn MP,Blake J,Bull K,Brandner S,Polke J,Davis M,Houlden H,Reilly MM (2011) GENETIC MUTATION FREQUENCY IN PATIENTS WITH HEREDITARY SENSORY AND AUTONOMIC NEUROPATHIES (HSAN) JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, 16, S93 - S93.
  23. Sadnicka A,Reilly MM,Mummery C,Brandner S,Hirsch N,Lunn MP (2011) Rituximab in the treatment of three coexistent neurological autoimmune diseases: chronic inflammatory demyelinating polyradiculoneuropathy, Morvan syndrome and myasthenia gravis. J Neurol Neurosurg Psychiatry, 82(2), 230 - 232. 10.1136/jnnp.2009.174888.
  24. Murphy SM,Polke J,Manji H,Blake J,Reiniger L,Sweeney M,Houlden H,Brandner S,Reilly MM (2011) A novel mutation in the nerve-specific 5'UTR of the GJB1 gene causes X-linked Charcot-Marie-Tooth disease. J Peripher Nerv Syst, 16(1), 65 - 70. 10.1111/j.1529-8027.2011.00321.x.
  25. Saifee TA,Elliott KJ,Rabin N,Yong KL,D'Sa S,Brandner S,Lunn MP,Blake J,Reilly MM (2011) Bortezomib-induced inflammatory neuropathy (vol 15, pg 366, 2010) J PERIPHER NERV SYST, 16(1), 74 - 74. 10.1111/j.1529-8027.2011.00315.x.
  26. Murphy SM,Davidson GL,Laura M,Salih M,Muntoni F,Lunn M,Blake J,Brandner S,Polke J,Davies M,Houlden H,Reilly MM (2011) Genetic mutation frequency in patients with hereditary sensory and autonomic neuropathies (HSAN) NEUROMUSCULAR DISORDERS, 21, S17 - S18.
  27. Cleary JO,Wiseman FK,Norris FC,Price AN,Choy M,Tybulewicz VL,Ordidge RJ,Brandner S,Fisher EM,Lythgoe MF (2011) Structural correlates of active-staining following magnetic resonance microscopy in the mouse brain. Neuroimage, 56(3), 974 - 983. 10.1016/j.neuroimage.2011.01.082.
  28. Saifee TA,Reilly MM,Ako E,Rugg-Gunn F,Brandner S,Lunn MP,Leary SM (2011) Sarcoidosis presenting as acute inflammatory demyelinating polyradiculoneuropathy. Muscle Nerve, 43(2), 296 - 298. 10.1002/mus.21890.
  29. Galavotti S,Shaked-Rabi M,Tulchinsky E,Brandner S,Jones C,Salomoni P (2011) THE METABOLIC AUTOPHAGY PATHWAY REGULATES MIGRATION AND INVASION IN GLIOMA NEURO-ONCOLOGY, 13, 10 - 10.
  30. Thom M,An S,Martinian L,Sisodiya SM,Dean A,McEvoy A,Brandner S,Toma A (2011) 101 DNTs: histological subtypes, molecular genetics and clinical correlations in an adult epilepsy series NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 37, 16 - 16.
  31. Revesz T,Schott JM,Reiniger L,Thom M,Holton JL,Grieve J,Brandner S,Warren JD (2011) Brain biopsy in dementia: clinical indications and neuropathological diagnostic approach NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 37, 10 - 10.
  32. Akhtar S,Wenborn A,Brandner S,Collinge J,Lloyd SE (2011) Sex effects in mouse prion disease incubation time. PLoS One, 6(12), e28741. 10.1371/journal.pone.0028741.
  33. Russo M,Laurá M,Polke JM,Davis MB,Blake J,Brandner S,Hughes RAC,Houlden H,Bennett DLH,Lunn MPT,Reilly MM (2011) Variable phenotypes are associated with PMP22 missense mutations Neuromuscular Disorders, 21(2), 106 - 114.
  34. Reiniger L,Lukic A,Linehan J,Rudge P,Collinge J,Mead S,Brandner S (2011) Tau, prions and Aβ: the triad of neurodegeneration. Acta Neuropathol, 121(1), 5 - 20. 10.1007/s00401-010-0691-0.
  35. Carswell C,Drynda R,Martins S,Clarke A,Brandner S,Mead S,Collinge J,Khalili-Shirazi A (2011) PAW35 Anti-prion protein monoclonal antibodies at low doses effectively treat prion disease in mice without side-effects (vol 81, pg e33, 2010) J NEUROL NEUROSUR PS, 82(7), 826 - 826. 10.1136/jnnp.2010.226340.63corr1.
  36. Kaski DN,Pennington C,Beck J,Poulter M,Uphill J,Bishop MT,Linehan JM,O'Malley C,Wadsworth JD,Joiner S,Knight RS,Ironside JW,Brandner S,Collinge J,Mead S (2011) Inherited prion disease with 4-octapeptide repeat insertion: disease requires the interaction of multiple genetic risk factors. Brain, 134(Pt 6), 1829 - 1838. 10.1093/brain/awr079.
  37. Banks GT,Haas MA,Line S,Shepherd HL,Alqatari M,Stewart S,Rishal I,Philpott A,Kalmar B,Kuta A,Groves M,Parkinson N,Acevedo-Arozena A,Brandner S,Bannerman D,Greensmith L,Hafezparast M,Koltzenburg M,Deacon R,Fainzilber M,Fisher EM (2011) Behavioral and other phenotypes in a cytoplasmic Dynein light intermediate chain 1 mutant mouse. J Neurosci, 31(14), 5483 - 5494. 10.1523/JNEUROSCI.5244-10.2011.
  38. Thom M,Toma A,An S,Martinian L,Hadjivassiliou G,Ratilal B,Dean A,McEvoy A,Sisodiya SM,Brandner S (2011) One hundred and one dysembryoplastic neuroepithelial tumors: an adult epilepsy series with immunohistochemical, molecular genetic, and clinical correlations and a review of the literature. J Neuropathol Exp Neurol, 70(10), 859 - 878. 10.1097/NEN.0b013e3182302475.
  39. Wadsworth JD,Dalmau-Mena I,Joiner S,Linehan JM,O'Malley C,Powell C,Brandner S,Asante EA,Ironside JW,Hilton DA,Collinge J (2011) Effect of fixation on brain and lymphoreticular vCJD prions and bioassay of key positive specimens from a retrospective vCJD prevalence study. J Pathol, 223(4), 511 - 518. 10.1002/path.2821.
  40. Reiniger L,Lukic A,Linehan J,Rudge P,Collinge J,Mead S,Brandner S (2011) Prion protein-induced tau phosphorylation: insight into a universal mechanism triggered by cerebral amyloid NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 37, 13 - 13.
  41. Edgeworth JA,Sicilia A,Linehan J,Brandner S,Jackson GS,Collinge J (2011) A standardized comparison of commercially available prion decontamination reagents using the Standard Steel-Binding Assay. J Gen Virol, 92(Pt 3), 718 - 726. 10.1099/vir.0.027201-0.
  42. Brandner S (2011) Diversity of prion diseases: (no) strains attached? Acta Neuropathol, 121(1), 1 - 4. 10.1007/s00401-010-0775-x.
  43. Robinson JP,Vanbrocklin MW,Lastwika KJ,McKinney AJ,Brandner S,Holmen SL (2011) Activated MEK cooperates with Ink4a/Arf loss or Akt activation to induce gliomas in vivo. Oncogene, 30(11), 1341 - 1350. 10.1038/onc.2010.513.
  44. Hutton EJ,Carty L,Laurá M,Houlden H,Lunn MP,Brandner S,Mirsky R,Jessen K,Reilly MM (2011) c-Jun expression in human neuropathies: a pilot study. J Peripher Nerv Syst, 16(4), 295 - 303. 10.1111/j.1529-8027.2011.00360.x.
  45. Saifee TA,Elliott KJ,Rabin N,Yong KL,D'Sa S,Brandner S,Lunn MP,Blake J,Reilly MM (2010) Bortezomib-induced inflammatory neuropathy. J Peripher Nerv Syst, 15(4), 366 - 368. 10.1111/j.1529-8027.2010.00287.x.
  46. Henriquez NV,Swales A,Jacques TS,Brandner S (2010) Gene expression profiling of brain tumours in a mouse model: insights into tumour-type specific transcripteome networks Neuropathology and Applied Neurobiology, 36(S1), 5 - 5.
  47. Lukic A,Wadsworth J,Brandner S,Rudge P,Hyare H,Collinge J,Reiniger L,Mead S,Gilmore C,Humberstone M (2010) POD01 Misleading MRI in two recent patients with variant Creutzfeldt-Jakob disease emphasises the importance of tissue diagnosis. J Neurol Neurosurg Psychiatry, 81(11), e42. 10.1136/jnnp.2010.226340.101.
  48. Murphy S,Brandner S,Polke J,Manji H,Houlden H,Reilly MM (2010) POG11 A novel mutation in the nerve-specific 5'-UTR of the Cx32 gene causing CMTX1. J Neurol Neurosurg Psychiatry, 81(11), e50. 10.1136/jnnp.2010.226340.133.
  49. Siddique D,Hyare H,Wroe S,Webb T,Macfarlane R,Rudge P,Collinge J,Powell C,Brandner S,So PW,Walker S,Mead S,Yousry T,Thornton JS (2010) Magnetization transfer ratio may be a surrogate of spongiform change in human prion diseases. Brain, 133(10), 3058 - 3068. 10.1093/brain/awq243.
  50. Revesz T,Schott JM,Holton JL,Reiniger L,Brandner S,Thom M,Warren JD (2010) Brain biopsy in dementia - clinical indications and diagnostic approach BRAIN PATHOLOGY, 20, 8 - 8.

Biography

I started my research career during Medical School in Göttingen, at the Max Planck Institute of Biophysical Chemistry with Professor Creutzfeldt, where I studied the projection of the thalamocortical auditory system in the cat, resulting in several research publications as first author. 

During my postgraduate training in Neuropathology, I joined the Institute of Neuropathology in Zurich, where I started my research on prion disease, resulting in seminal publications in Nature and PNAS. 

After qualifying as a Consultant Neuropathologist in 1998, I established my own research group and developed mouse models to study neural development and brain tumours. In 2001, I was recruited through the MRC international recruitment scheme to join the MRC Prion Unit at UCL Institute of Neurology. 

In 2004 I was appointed as Chair of Neuropathology and Head of the Division of Neuropathology at Queen Square, one of the largest academic neuropathology departments in the UK.

At the MRC Prion Unit and the Institute of Neurology I integrated clinical neuropathology with experimental models on neurodegenerative diseases including prion diseases, which still remain a strong focus in my highly collaborative research. I am an expert on the pathology of both human and experimental models of prion disease worldwide and I maintains a close collaboration with the MRC Prion Unit and the National Prion Clinic at the National Hospital, Queen Square. 

I recently conducted a study “prevalence screening for the presence of vCJD prions” for the HPA, which has major implications for UK policy. At the Institute of Neurology, I also expanded my research on brain tumours which resulted in a number of excellent publications in Development and EMBO Journal. I developed a strong team working on brain cancer, and established close collaborations between UCL Cancer Centre and the Brain Tumour Unit at the National Hospital. I contribute nationally to brain cancer research in my role as council member of the British Neuro-oncology Society. Academic pathology and research on experimental models and their translation to human diseases are recognised key development areas in the UK. 











Qualifications

  • 1991: Privatdozent, Georg-August-Universität Göttingen
  • 1989: Doctor of Medicine, Georg-August-Universität Göttingen

Keywords

  • Brain
  • Brain tumours
  • Brain tumours in adults
  • Brain tumours in children
  • Cancer cell cycle
  • Cell culture
  • Cell transplantation
  • Cerebellum
  • Confocal microscopy
  • Creutzfeldt- Jakob disease (CJD)
  • Development
  • Differentiation
  • ES cell manipulations
  • Fluorescence microscopy techniques
  • Gene expression
  • Gene expression profiling - tissue level
  • Genetic manipulation (including knockout/knockin)
  • Genetically encoded reporters/indicators
  • Genomic analyses
  • Histology
  • Laser Capture
  • Light microscopic techniques
  • MRNA
  • Microarrays
  • Microdissection
  • Mouse
  • Neural stem cells
  • Neuropathology
  • Oligodendrocytes
  • Prion disease
  • Prion diseases
  • Stem cells
  • Transgenic mice
  • Transmissible spongiform encephalopathies (TSEs)
  • Viral vectors