CV Science

Alexis Brice MD, Prof of Medical Genetics

Course and current status

Current positions:

Professor of Medical Genetics, Pierre and Marie Curie University (UPMC).

Neurologist (Medical Genetics), Federation of Neurology, Pitié-Salpêtrière University Hospital.

Head, National Institute for Neuroscience, Cognitive Sciences, Neurology and Psychiatry. 

Head of research group "Molecular bases, physiopathology and treatment of neurodegenerative disorders", Cricm/ Inserm UMR_S975/CNRS UMR 7225/UPMC.

Head, DNA and Cell bank, CRicm.

Head, National Reference Center for Neurogenetics, Pitié-Salpêtrière University Hospital.

Previous professional experience:

2001-2009: Head, Department of Genetics and Cytogenetics, Pitié-Salpêtrière University Hospital.

1988-1992: Assistant in Cell Biology, UPMC-Paris 6.

Education and training:

1988: Doctor of Medicine (Silver Medal).

1988: Master of Science in Biochemistry, UPMC.

1987-1988: Residency in Neurology, Pitié-Salpêtrière Hospital.

1981-1984: Residency in Neurology, Pitié-Salpêtrière Hospital.

Member of Learned Societies:

French National Academy of Medicine (elected corresponding member, 2007-).

European Society for Human Genetics (member of the board, 2003-2008; member of the scientific program committee, 2010-).

American Society for Human Genetics.

American Academy of Neurology (executive committee for neurogenetics, 1998-2002).

European College of Neuropsychopharmacology (Scientific advisory panel for neurological disorders, 2005-2008).

Movement Disorders Society.

Member of institutional scientific advisory boards:

Pitié-Salpêtrière University Hospital (President of the research committee, 2003-).

UPMC-Medical School (2006-2010).

Federative Institute for Research in the Neurosciences (IFR070, 2003-2008).

Member of scientific advisory boards of funding organizations:

The Wellcome Trust Neuroscience & Mental Health Funding Committee (2004-2006).

Gis Maladies Rares (2002-2004); GenHomme Network (2002-2003).

National PHRC (Hospital program for clinical research) (2004-2006).

AVENIR (INSERM), vice-president (2004-2008).

ANR (National Research Agencies) programs: “Neuroscience, Neurology, and Psychiatry”, coordinator (2005-2008); “Longevity and Aging”, coordinator (2007); “Neurological and Psychiatric Disorders,” coordinator (2008).

Research Foundation Flanders, FWO-expert panel Bio 1 (Molecular and Cellular Biology) (2010-).

Scientific summary

Alexis Brice is a specialist of molecular neurogenetics. His team has contributed to the extensive renewal of the nosology of spinocerebellar degeneration by identifying many of the genes associated with cerebellar ataxias and spastic paraplegias. His group has helped to extend the concept of polyglutamine disorders in the spinocerebellar ataxias and to analyse the behaviour of CAG repeat expansions and their consequences at the cellular level. This recently led to the identification of the PML protein as a potential therapeutic target for the treatment of spinocerebellar ataxia 7. Similarly, his group has extensively characterized the molecular bases of spastic paraplegias, a very heterogeneous group of neurodegenerative disorders. These discoveries are now widely applied in clinical practice for the classification and the molecular diagnosis of these genetic conditions. Since approximately 50% of spinocerebellar degenerations cannot be explained by already identified genes, Dr. Brice’s team has begun “next generation” sequencing in a large number of families in order to determine the genetic basis of new forms of these diseases.

Perhaps more widely known is the contribution of this group to the elucidation of the molecular bases of familial Parkinson’s disease. It was the first group to illustrate the major role of the Parkin gene in patients with early onset in Europe, and to demonstrate the frequency of genomic rearrangements in this gene. This led the group to generate the first mouse model of Parkin-dependent Parkinson’s disease by inactivation of the gene and to demonstrate the role of Parkin in non-canonical ubiquitylation. His group, which was the first to show the interaction between Parkin and mitochondria, is now analysing the mechanisms by which Parkin and PINK1, another gene responsible for early-onset parkinsonism, affect mitochondrial dynamics and mitophagy. He also found that duplications of the SNCA gene are responsible for autosomal dominant Parkinson’s disease, demonstrating the pathological effect of an increase in the dosage of this gene. In addition, the group has shown that a particular mutation in the LRRK2 gene, involved in autosomal dominant Parkinson’s disease, is found in over 1/3 of all patients from North Africa. These results, combined with those they recently obtained in a French genome-wide association study, have greatly modified our understanding of the molecular bases of Parkinson’s disease by demonstrating an unexpectedly high frequency of a genetic component in apparently sporadic cases in certain populations. The group is now actively developing animal models based on these new discoveries, in order to better understand the mechanisms of neurodegeneration in Parkinson’s disease and the interactions among the genes involved, as well as to test potential treatments.