Bio

Academic Appointments


Administrative Appointments


  • Assistant Professor, University of California, San Francisco (1978 - 1983)
  • Directeur de Recherche, Centre National de la Recherche Scientifique, France (1983 - 2006)
  • Professor, Institut Pasteur, Paris (1989 - 2006)
  • Consulting Professor, Stanford University (2007 - Present)

Honors & Awards


  • Ordre National du Merite, French Government

Research & Scholarship

Current Research and Scholarly Interests


The lesions of Parkinson's disease (PD) spread within the central nervous system (CNS) with characteristics of prion diseases. The prion in this case is a misfolded form of alpha-synuclein. We are investigating the mechanism of spread on alpha-synuclein prions with a special attention to axonal transport and transfer of prions between neurons. Understanding these pathways could lead to using drugs to slow down or halt disease progression.

Publications

Journal Articles


  • The NeST Long ncRNA Controls Microbial Susceptibility and Epigenetic Activation of the Interferon-gamma Locus CELL Gomez, J. A., Wapinski, O. L., Yang, Y. W., Bureau, J., Gopinath, S., Monack, D. M., Chang, H. Y., Brahic, M., Kirkegaard, K. 2013; 152 (4): 743-754

    Abstract

    Long noncoding RNAs (lncRNAs) are increasingly appreciated as regulators of cell-specific gene expression. Here, an enhancer-like lncRNA termed NeST (nettoie Salmonella pas Theiler's [cleanup Salmonella not Theiler's]) is shown to be causal for all phenotypes conferred by murine viral susceptibility locus Tmevp3. This locus was defined by crosses between SJL/J and B10.S mice and contains several candidate genes, including NeST. The SJL/J-derived locus confers higher lncRNA expression, increased interferon-? (IFN-?) abundance in activated CD8(+) T cells, increased Theiler's virus persistence, and decreased Salmonella enterica pathogenesis. Transgenic expression of NeST lncRNA alone was sufficient to confer all phenotypes of the SJL/J locus. NeST RNA was found to bind WDR5, a component of the histone H3 lysine 4 methyltransferase complex, and to alter histone 3 methylation at the IFN-? locus. Thus, this lncRNA regulates epigenetic marking of IFN-?-encoding chromatin, expression of IFN-?, and susceptibility to a viral and a bacterial pathogen.

    View details for DOI 10.1016/j.cell.2013.01.015

    View details for Web of Science ID 000314945600010

    View details for PubMedID 23415224

  • Neuron-to-neuron transmission of alpha-synuclein fibrils through axonal transport ANNALS OF NEUROLOGY Freundt, E. C., Maynard, N., Clancy, E. K., Roy, S., Bousset, L., Sourigues, Y., Covert, M., Melki, R., Kirkegaard, K., Brahic, M. 2012; 72 (4): 517-524

    Abstract

    The lesions of Parkinson disease spread through the brain in a characteristic pattern that corresponds to axonal projections. Previous observations suggest that misfolded ?-synuclein could behave as a prion, moving from neuron to neuron and causing endogenous ?-synuclein to misfold. Here, we characterized and quantified the axonal transport of ?-synuclein fibrils and showed that fibrils could be transferred from axons to second-order neurons following anterograde transport.We grew primary cortical mouse neurons in microfluidic devices to separate somata from axonal projections in fluidically isolated microenvironments. We used live-cell imaging and immunofluorescence to characterize the transport of fluorescent ?-synuclein fibrils and their transfer to second-order neurons.Fibrillar ?-synuclein was internalized by primary neurons and transported in axons with kinetics consistent with slow component-b of axonal transport (fast axonal transport with saltatory movement). Fibrillar ?-synuclein was readily observed in the cell bodies of second-order neurons following anterograde axonal transport. Axon-to-soma transfer appeared not to require synaptic contacts.These results support the hypothesis that the progression of Parkinson disease can be caused by neuron-to-neuron spread of ?-synuclein aggregates and that the anatomical pattern of progression of lesions between axonally connected areas results from the axonal transport of such aggregates. That the transfer did not appear to be trans-synaptic gives hope that ?-synuclein fibrils could be intercepted by drugs during the extracellular phase of their journey.

    View details for DOI 10.1002/ana.23747

    View details for Web of Science ID 000310544900009

    View details for PubMedID 23109146

  • Multiple Sclerosis and Viruses ANNALS OF NEUROLOGY Brahic, M. 2010; 68 (1): 6-8

    Abstract

    Discussing the problem of multiple sclerosis and viruses should not be limited to reviewing the epidemiological evidence in favor, or against, a particular candidate, such as Epstein-Barr virus or human herpes virus 6. In this text, I discuss the difficulty of going from association to causation in human epidemiology; the fact that viruses can trigger or prevent autoimmunity; the problem of our very limited knowledge of the viruses that we harbor as part of our metagenome; and the role of such viral flora in multifactorial diseases and also, possibly, in health.

    View details for DOI 10.1002/ana.22057

    View details for Web of Science ID 000279361000003

    View details for PubMedID 20582990

  • Axon-Myelin Interactions during a Viral Infection of the Central Nervous System PLOS PATHOGENS Brahic, M., Roussarie, J. 2009; 5 (9)

    View details for DOI 10.1371/journal.ppat.1000519

    View details for Web of Science ID 000270804900001

    View details for PubMedID 19779566

  • Axon Myelin Transfer of a Non-Enveloped Virus PLOS ONE Roussarie, J., Ruffie, C., Edgar, J. M., Griffiths, I., Brahic, M. 2007; 2 (12)

    Abstract

    We showed previously that Theiler's virus, a neurotropic non-enveloped picornavirus of mouse, traffics from the axon of infected neurons into the surrounding myelin. When this traffic is interrupted, as in the shiverer mouse which bears a mutation in the myelin basic protein gene, the virus is unable to persist in the central nervous system. In the present work, we used the Wld(s) mutant mouse, a strain in which axonal degeneration is considerably slowed down, to show that axon to myelin traffic takes place in the absence of axon degeneration. Our results suggest the existence of a mechanism of transfer of axonal cytoplasm into the myelin which Theiler's virus might exploit to ensure its persistence.

    View details for DOI 10.1371/journal.pone.0001331

    View details for Web of Science ID 000207459700003

    View details for PubMedID 18159229

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