Salmonella • typhoid • complex disease • animal model • mutagenesis
My research focuses on identifying and characterizing genes involved in the host immune response to pathogenic Salmonella using mouse models of the disease. Salmonella are ubiquitous, facultative intracellular Gram-negative bacteria causing human diseases (typhoid fever and salmonellosis) of increasingly important public health concern both in developed and developing countries. Salmonella Typhi is the causative agent of typhoid fever and Salmonella Typhimurium and Enteritidis are associated with frequent outbreaks of food-borne gastroenteritis (salmonellosis). Multidrug resistant non-typhoidal Salmonella (NTS) infections are also increasingly frequent in developing countries. My lab is using different models of infection (systemic, chronic carriage and intestinal infection) and genetic approaches (positional cloning of Mendelian and complex phenotypes and chemical mutagenesis) to study the complex mechanisms underlying the host response to Salmonella infection.
Eva MM, Yuki KE, Dauphinee SM, Schwartzentruber JA, Pyzik M, Paquet M, Lathrop M, Majewski J, Vidal S.M., and D. Malo. 2014. ENU-induced mutation in STAT4 increases susceptibility to Salmonella Typhimurium infection in mice as a result of an early innate defect in NK cell-derived IFNγ-mediated immunity and induction of a subset of dendritic cells. J Immunol 192: 259-270. PMCID: PMC4276919.
Papapietro O, Teatero S, Zhu L, Diez E, Thanabalasuriar A, Yuki K, Marcinkiewicz MM, Malo D & S Gruenheid. 2013. Activation of Rspo2/Wnt signaling regulates susceptibility to fatal infectious diarrhea. Nature Commun 4:1898. doi: 10.1038/ncomms2816. PMID: 23695692.
Yuki K.E., Eva M.M., Richer E., Chung D., Paquet M., Cellier M, Canonne-Hergaux F., Vaulont S., Vidal S.M., and D. Malo. 2013. Suppression of hepcidin expression and iron overload mediate Salmonella susceptibility in ankyrin 1 ENU-induced mutant. PloS One 8(2):e55331. PMID: 23390527.
Khan R., Sancho-Shimizu V., Prendergast C., Roy M.-F., Loredo-Osti J.C., Malo D. 2012. Refinement of the genetics of the host response to Salmonella infection in MOLF/Ei: regulation of type 1 IFN and TRP3 pathways by Ity2. Genes Immun 2:175-83. PMID: 21956657.
Richer E, Prendergast C, Zhang D-E, Qureshi ST, Vidal SM and Malo D. 2010. ENU induced mutation in Usp18 increases susceptibility to Salmonella Typhimurium: important role of IFN-a/b signaling. J Immunol. 185: 3593-3601. PMID: 20693420.