UCL Institute of Neurology


Prof. Sebastian Brandner (Head of Division)

Prof Sebastian Brandner

Prof Sebastian Brandner


Institute of Neurology , UCL
Queen Square House


  • Professor of Neuropathology
    Neurodegenerative Diseases
    Institute of Neurology

Joined UCL


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 

Award year Qualification Institution
1991 Priv-Doz
Clinical Medicine
Georg-August-Universität Göttingen
1989 MD
Doctor of Medicine
Clinical Medicine
Georg-August-Universität Göttingen

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. 

Diagnostic Service 

Molecular Neuro-Oncology: I provide a comprehensive Neuro-oncology service for the National Hospital (more than 200 tests annually) and for referring Hospitals (more than 200 tests p.a.). We routinely perform tests for LOH1p/19q, EGFR amplification, IDH mutation (immunohistochemical detection and sequencing) and other markers that are relevant for the prognosis of high grade gliomas, (LOH10q, PDGFRa, LOH NF1) and MGMT Promoter methylation. We test for the KIAA:BRAF fusion transcript and the V600E mutation, which have diagnostic and prognostic relevance for pilocytic astrocytomas, and other low grade glial tumours of the nervous system (read more on molecular pathology tests).

Diagnostic Neuro-oncology: In rotation with all other consultants in the department, we diagnose all surgical Neuropathology in the Department. We diagnose more than 1100 brain tumours and pituitary adenomas every year. All consultants in the department have the expertise to diagnose common and rare brain cancers and other surgical neuropathology cases. Soft tissue and haematological malignancies are routinely referred for expert second opinion.

Prion disease: In close cooperation with the National Prion Clinic and the MRC Prion Unit I carry out ca 50 post mortem examinations of sporadic, familial and acquired prion disease every year. Thanks to the cooperation with families to consent the brain tissue to be used for research, we were able to build up a unique resource of research tissues with all types of prion diseases.

Peripheral Neuropathies: Together with Dr Phadke, I diagnose approximately 120 peripheral nerve biopsies per year. Most peripheral Neuropathies are of inflammatory nature and we have developed considerable expertise and interest in the differential diagnosis of inflammatory neuropathies. A broad range of specialist techniques are used in the diagnosis of inflammatory neuropathies. We have a close interaction with the clinical team to discuss the investigation of each neuropathy individually (read  more about the centre for Neuromuscular Diseases). 

Professional Affiliations

· Royal College of Pathologists (www.rcpath.org)

· British Society of Neuropathologists (www.bns.org.uk)

· American Association of Neuropathologists (AANP)

· Society for Neuroscience (SfN, USA)

· German Society of Neuroscience

· British Neuro-Oncology Society (www.bnos.org.uk)

· Swiss Society of Experimental Biology (USGEB)

Top 10 publications

  • Gill N, Spencer Y, Richard-Loendt A, Kelly C, Dabaghian R, Boyes L, Linehan J, Simmons M, Webb P, Bellerby P, Andrews N, Hilton DA, Ironside J, Beck J, Poulter M, Mead S, Brandner S. Prevalent abnormal prion protein in human appendices after cattle BSE epizootic. British Medical Journal. 2013;
  • Henriquez NV, Forshew T, Tatevossian R, Ellis M, Richard-Loendt A, Rogers HA, Jacques TS, Garcia Reitboeck P, Pearce K, Sheer D, Grundy RG, Brandner S. Comparative expression analysis reveals lineage relationships between human and murine gliomas and a dominance of glial signatures during tumour propagation in vitro. Cancer Res. 2013 Jul 25.
  • Reiniger L, Mirabile I, Lukic A, Wadsworth JD, Linehan J, Groves M, Lowe J, Druyeh R, Collinge J, Mead S, Brandner S. Filamentous white matter prion protein deposition is a distinctive feature of multiple inherited prion diseases. Acta Neuropathologica Communications. 2013;1:1-17.
  • Jacques TS, Swales A, Brzozowski MJ, Henriquez NV, Linehan JM, Mirzadeh Z, O'Malley C, Naumann H, Alvarez-Buylla A, Brandner S. Combinations of genetic mutations in the adult neural stem cell compartment determine brain tumour phenotypes. EMBO J. 2010 Jan 6;29(1):222-35
  • Nayeem N, Kerr F, Naumann H, Linehan J, Lovestone S, Brandner S. Hyperphosphorylation of tau and neurofilaments and activation of CDK5 and ERK1/2 in PTEN-deficient cerebella. Mol Cell Neurosci. 2007 Mar;34(3):400-8
  • Haegele L, Ingold B, Naumann H, Tabatabai G, Ledermann B, Brandner S. Wnt signalling inhibits neural differentiation of embryonic stem cells by controlling bone morphogenetic protein expression. Mol Cell Neurosci. 2003 Nov;24(3):696-708.
  • Marino S, Krimpenfort P, Leung C, van der Korput HA, Trapman J, Camenisch I, Berns A, Brandner S. PTEN is essential for cell migration but not for fate determination and tumourigenesis in the cerebellum. Development. 2002 Jul;129(14):3513-22
  • Benninger Y, Marino S, Hardegger R, Weissmann C, Aguzzi A, Brandner S. Differentiation and histological analysis of embryonic stem cell-derived neural transplants in mice. Brain Pathol. 2000 Jul;10(3):330-41.
  • Brandner S. Raeber A, Sailer A, Blattler T, Fischer M, Weissmann C, Aguzzi A. Normal host prion protein (PrPC) is required for scrapie spread within the central nervous system. Proc Natl Acad Sci U S A. 1996 Nov 12;93(23):13148-51.
  • Brandner S. Isenmann S, Raeber A, Fischer M, Sailer A, Kobayashi Y, Marino S, Weissmann C, Aguzzi A. Normal host prion protein necessary for scrapie-induced neurotoxicity. Nature. 1996 Jan 25;379(6563):339-43.