mouse genetic models • virus infections • innate immunity • complex traits analysis • primary human cells
My research focuses on why certain individuals are extremely vulnerable to a viral infection and develop severe diseases whereas others remain unharmed when exposed to the same pathogen. Herpes simplex encephalitis, influenza pneumonia, and viral myocarditis are severe but relatively rare occurrences of infections with viruses that are common in the general population. My laboratory uses specialized mouse genetic models that replicate human diseases to parse genes, proteins, and cells of the host that are implicated in the infection process. We have found proteins involved in virus recognition, signal transduction kinases, and transcription factors, which are critical to the outcome of infection. With this information, we search for small molecules that target those mechanisms to improve virus-induced pathologies.
Caignard G, Leiva-Torres GA, Leney-Greene M, Charbonneau B, Dumaine A, Fodil-Cornu N, Pyzik M, Cingolani P, Schwartzentruber J, Dupaul-Chicoine J, Guo H, Saleh M, Veillette A, Lathrop M, Blanchette M, Majewski J, Pearson A, Vidal SM. Genome-wide mouse mutagenesis reveals CD45-mediated T cell function as critical in protective immunity to HSV-1. PLoS Pathog. 2013 Sep;9(9):e1003637. doi:10.1371/journal.ppat.1003637.
Pothlichet J, Meunier I, Davis BK, Ting JP, Skamene E, von Messling V, Vidal SM. Type I IFN triggers RIG-I/TLR3/NLRP3-dependent inflammasome activation in influenza A virus infected cells. PLoS Pathog. 2013 Apr;9(4):e1003256. doi:10.1371/journal.ppat.1003256.
Boivin GA, Pothlichet J, Skamene E, Brown EG, Loredo-Osti JC, Sladek R, Vidal SM. Mapping of clinical and expression quantitative trait loci in a sex-dependent effect of host susceptibility to mouse-adapted influenza H3N2/HK/1/68. J Immunol. 2012 Apr 15;188(8):3949-60. doi: 10.4049/jimmunol.1103320. Epub 2012 Mar 16.
Wiltshire SA, Leiva-Torres GA, Vidal SM. Quantitative trait locus analysis, pathway analysis, and consomic mapping show genetic variants of Tnni3k, Fpgt, or H28 control susceptibility to viral myocarditis. J Immunol. 2011 Jun 1;186(11):6398-405. doi: 10.4049/jimmunol.1100159. Epub 2011 Apr 27.
Pyzik M, Charbonneau B, Gendron-Pontbriand EM, Babi_ M, Krmpoti_ A, Jonji_ S, Vidal SM. Distinct MHC class I-dependent NK cell-activating receptors control cytomegalovirus infection in different mouse strains. J Exp Med. 2011 May 9;208(5):1105-17. doi: 10.1084/jem.20101831. Epub 2011 Apr 25.