Human genetics of neurological disorders
The main focus of the laboratory is the study of the genetic factors involved in complex neurological diseases and their interaction with clinical and environmental factors. For this purpose, we integrate different layers of information, including whole genome profiling (genetic and transcriptomic) and clinical characteristics of each subject to better understand the pathophysiological mechanisms that contribute to the disease. We believe that this multi-disciplinary approach contributes to disentangle the complexity of the disease, elucidating processes that could be relevant in the identification of novel therapeutic targets, as well as in the field of personalized medicine.
Our main interest is on Multiple Sclerosis (MS) although other neurological disorders are currently studied such has neuropathic pain and other neurodegenerative diseases.
The laboratory hosts a group of scientists with different expertise (biologists, bioinformaticians and neurologists); it takes advantage of a strong collaboration with the Neurological Department, allowing a precise clinical characterization of studied subjects, and of a large biobank of more than 3,000 patients affected with MS, about 1,000 patients affected with neurodegenerative disorders and 800 healthy controls. We have a strong experience in MS pharmacogenomics field, with several studies performed to identify biomarkers of response to different MS treatments.
Moreover, the laboratory is currently active in two projects funded by EU: The MultipleMS and the Pain-NET projects.
- The first one is aimed to develop novel personalized medicine approaches for MS patients by integrating clinical information, molecular data and exposure to environmental factors in a cohort of tens of thousands of subjects.
- The second project is aimed to better investigate and identify new biomarkers of chronic pain and analgesic responsiveness using a combined approach (next generation sequencing, epigenetics and proteomics).
Malhotra S, Sorosina M, Río J, Peroni S, Midaglia L, Villar LM et al. NLRP3 polymorphisms and response to interferon-beta in multiple sclerosis patients. Mult Scler. 2017 Nov 1:1352458517739137.
Clarelli F, Liberatore G, Sorosina M, Osiceanu AM, Esposito F, Mascia E et al. Pharmacogenetic study of long-term response to interferon-ß treatment in multiple sclerosis. Pharmacogenomics J. 2017 Jan;17(1):84-91.
Esposito F, Sorosina M, Ottoboni L, Lim ET, Replogle JM, Raj T et al. A pharmacogenetic study implicates SLC9A9 in multiple sclerosis disease activity. Ann Neurol. 2015 Jul;78(1):115-27.
Sorosina M, Esposito F, Guaschino C, Clarelli F, Barizzone N, Osiceanu AM et al. Inverse correlation of genetic risk score with age at onset in bout-onset and progressive-onset multiple sclerosis. Mult Scler. 2015 Oct;21(11):1463-7.
A.H. Beecham, N.A. Patsopoulos, D.K. Xifara, M.F. Davis, A. Kemppinen, C. et al. International Multiple Sclerosis Genetics Consortium (IMSGC). Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat Genet. 2013 Nov;45(11):1353-60.
Patsopoulos NA, Barcellos LF, Hintzen RQ, Schaefer C, van Duijn CM, Noble JA et al. Fine-mapping the genetic association of the major histocompatibility complex in multiple sclerosis: HLA and non-HLA effects. PLoS Genet. 2013 Nov;9(11):e1003926.
International Multiple Sclerosis Genetics Consortium. Network-based Multiple Sclerosis pathway analysis with GWAS data from 15,000 cases and 30,000 controls. Am J Hum Genet. 2013 Jun 6;92(6):854-65.
Martinelli-Boneschi F, Esposito F, Brambilla P, Lindström E, Lavorgna G, Stankovich J et al. A genome-wide association study in progressive multiple sclerosis. Mult Scler. 2012 Oct;18(10):1384-94.
Patsopoulos NA, the Bayer Pharma MS Genetics Working Group, the Steering Committees of Studies Evaluating IFNβ-1b and a CCR1-Antagonist, ANZgene Consortium, GeneMSA, International Multiple Sclerosis Genetics Consortium et al. Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci. Ann Neurol. 2011 Dec;70(6):897-912.
International Multiple Sclerosis Genetics Consortium, Wellcome Trust Case Control Consortium 2, Sawcer S, Hellenthal G, Pirinen M, Spencer CC et al. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 2011 Aug 10;476(7359):214-9.