Our group is interested in both fundamental and clinically-oriented research projects in inflammatory/demyelinating diseases of the central nervous system (CNS), and in particular on the pathogenesis and regulation of Multiple Sclerosis (MS). Our major interests are (i) the search for new biomarkers for MS inflammation and neurodegeneration, such as anti-myelin antibodies, interleukins and neurofilaments, and (ii) the identification of the mechanisms of action of current MS therapies, such as interferon (IFN)-beta, glatiramer acetate (GA) and natalizumab. In this context, we recently demonstrated that IFN-beta, a disease-modifying drug with strong anti-inflammatory properties, modulates the production of brain-derived neurotrophic factor, indicating that IFN-beta may also contribute directly to neuroprotection in MS patients (J Neuroimmunol, 2008). Other studies from our group indicate that GA inhibits pathogenic human T cell differentiation (J Neuroimmunol, 2007) and affects human monocytes by triggering a bias toward a less inflammatory profile (Proc Natl Acad Sci U S A, 2009).
Multiple Sclerosis (MS) and demyelinating diseases of the CNS
Experimental Autoimmune Encephalitis (EAE)
Biomarkers of the serum and the cerebrospinal fluid in MS
Study of neuroprotective factors in EAE and MS
Study of Human Herpes-6 variant A and B in sporadic encephalitis
Because of its many similarities to MS, experimental autoimmune encephalitis (EAE), the animal model of MS, is regularly used in our laboratory to study MS pathogenesis and regulation. As a main scientific breakthrough, we found that hepatocyte growth factor (HGF), a paracrine cellular growth, motility and morphogenic factor, inhibits CNS autoimmunity by inducing tolerogenic dendritic cells and regulatory T cells (Proc Natl Acad Sci U S A, 2010). As our data also indicate a role for HGF in neuroprotection (Eur J Immunol, 2005), we are currently developing new animal models to study the neuroprotective effects of HGF separate from its immune-regulating properties.
We have developed during the last five years collaborative studies with national and international laboratories of neuroimmunology in Zurich (USZ), Lausanne (CHUV) and San Francisco (UCSF).
The major research topics of our group are:
Benkhoucha M, Santiago-Raber ML, Schneiter G, Chofflon M, Funakoshi H, Nakamura T, Lalive PH.(2010)Hepatocyte growth factor inhibits CNS autoimmunity by inducing tolerogenic DCs and CD25+Foxp3+ regulatory T cells.
Proceedings of the National Academy of Sciences of the United States of America, vol. 107(14) pp. 6424-6429
Burger D, Molnarfi N, Weber MS, Brandt KJ, Benkhoucha M, Gruaz L, Chofflon M, Zamvil SS, Lalive PH (2009)Glatiramer acetate increases IL-1 receptor antagonist but decreases T cell-induced IL-1beta in human monocytes and multiple sclerosis.Proceedings of the National Academy of Sciences of the United States of America, vol. 106(11) pp. 4355-4359
Lalive PH, Menge T, Delarasse C, Della Gaspera B, Pham-Dinh D, Villoslada P, von Büdingen HC, Genain CP.(2006)Antibodies to native myelin oligodendrocyte glycoprotein are serologic markers of early inflammation in multiple sclerosis.Proceedings of the National Academy of Sciences of the United States of America, 2006 vol. 103(7) pp. 2280-2285
University Medical Center
Département de Pathologie et Immunologie
Geneva University Hospital
Département des Neurosciences Cliniques
Service de Neurologie, Neuroimmunologie
Email: Patrice (dot) Lalive (at) hcuge (dot) ch