My laboratory is concerned with host defense against intracellular infection and how intracellular microbes disrupt cellular functions to favor their survival. Because of our interest in the role of macrophages in host defense, one focus of the laboratory is to identify pathways that regulate cell activation is response to key agonists such as IFN-y and bacterial lipopolysaccharide. This research has led to the identification of novel signaling pathways that regulate macrophage function. The second major interest in the laboratory is to understand the strategies used by intracellular pathogens to effectively prevent macrophage activation. This research focuses on identifying the pathways and molecules in macrophages targeted by intracellular pathogens and the corresponding microbial virulence factors involved. Pathogens under study include, Leishmania donovani, M. tuberculosis and Salmonella.
(2008 – Present)
Chan BC, Ip M, Gong H, Lui SL, See RH, Jolivalt C, Fung KP, Leung PC, Reiner NE, Lau CB. Synergistic effects of diosmetin with erythromycin against ABC transporter over-expressed methicillin-resistant Staphylococcus aureus (MRSA) RN4220/pUL5054 and inhibition of MRSA pyruvate kinase. Phytomedicine. 2013 May 15;20(7):611-4.
Thi EP, Hong CJ, Sanghera G, Reiner NE. Identification of the Mycobacterium tuberculosis protein PE-PGRS62 as a novel effector that functions to block phagosome maturation and inhibit iNOS expression. Cell Microbiol. 2013 May;15(5):795-808.
Kumar NS, Amandoron EA, Cherkasov A, Finlay BB, Gong H, Jackson L, Kaur S, Lian T, Moreau A, Labrière C, Reiner NE, See RH, Strynadka NC, Thorson L, Wong EW, Worrall L, Zoraghi R, Young RN. Optimization and structure-activity relationships of a series of potent inhibitors of methicillin-resistant Staphylococcus aureus (MRSA) pyruvate kinase as novel antimicrobial agents. Bioorg Med Chem. 2012 Dec 15;20(24):7069-82.
Thi EP, Lambertz U, Reiner NE. Class IA phosphatidylinositol 3-kinase p110α regulates phagosome maturation. PLoS One. 2012;7(8):e43668.
Thi EP, Reiner NE. Phosphatidylinositol 3-kinases and their roles in phagosome maturation. J Leukoc Biol. 2012 Sep;92(3):553-66.
Thi EP, Lambertz U, Reiner NE. Sleeping with the enemy: how intracellular pathogens cope with a macrophage lifestyle. PLoS Pathog. 2012;8(3):e1002551.
Lambertz U, Silverman JM, Nandan D, McMaster WR, Clos J, Foster LJ, Reiner NE. Secreted virulence factors and immune evasion in visceral leishmaniasis. J Leukoc Biol. 2012 Jun;91(6):887-99.
Nandan D, Camargo de Oliveira C, Moeenrezakhanlou A, Lopez M, Silverman JM, Subek J, Reiner NE. Myeloid cell IL-10 production in response to leishmania involves inactivation of glycogen synthase kinase-3β downstream of phosphatidylinositol-3 kinase. J Immunol. 2012 Jan 1;188(1):367-78.
Axerio-Cilies P, See RH, Zoraghi R, Worral L, Lian T, Stoynov N, Jiang J, Kaur S, Jackson L, Gong H, Swayze R, Amandoron E, Kumar NS, Moreau A, Hsing M, Strynadka NC, McMaster WR, Finlay BB, Foster LJ, Young RN, Reiner NE, Cherkasov A. Cheminformatics-driven discovery of selective, nanomolar inhibitors for staphylococcal pyruvate kinase. ACS Chem Biol. 2012 Feb 17;7(2):350-9.
Martínez-Gutierrez F, Thi EP, Silverman JM, de Oliveira CC, Svensson SL, Vanden Hoek A, Sánchez EM, Reiner NE, Gaynor EC, Pryzdial EL, Conway EM, Orrantia E, Ruiz F, Av-Gay Y, Bach H. Antibacterial activity, inflammatory response, coagulation and cytotoxicity effects of silver nanoparticles. Nanomedicine. 2012 Apr;8(3):328-36.
Zoraghi R, Worrall L, See RH, Strangman W, Popplewell WL, Gong H, Samaai T, Swayze RD, Kaur S, Vuckovic M, Finlay BB, Brunham RC, McMaster WR, Davies-Coleman MT, Strynadka NC, Andersen RJ, Reiner NE. Methicillin-resistant Staphylococcus aureus (MRSA) pyruvate kinase as a target for bis-indole alkaloids with antibacterial activities. J Biol Chem. 2011 Dec 30;286(52):44716-25.
Chan BC, Ip M, Lau CB, Lui SL, Jolivalt C, Ganem-Elbaz C, Litaudon M, Reiner NE, Gong H, See RH, Fung KP, Leung PC. Synergistic effects of baicalein with ciprofloxacin against NorA over-expressed methicillin-resistant Staphylococcus aureus (MRSA) and inhibition of MRSA pyruvate kinase. J Ethnopharmacol. 2011 Sep 1;137(1):767-73.
Zoraghi R, See RH, Axerio-Cilies P, Kumar NS, Gong H, Moreau A, Hsing M, Kaur S, Swayze RD, Worrall L, Amandoron E, Lian T, Jackson L, Jiang J, Thorson L, Labriere C, Foster L, Brunham RC, McMaster WR, Finlay BB, Strynadka NC, Cherkasov A, Young RN, Reiner NE. Identification of pyruvate kinase in methicillin-resistant Staphylococcus aureus as a novel antimicrobial drug target. Antimicrob Agents Chemother. 2011 May;55(5):2042-53.
Silverman JM, Reiner NE. Leishmania exosomes deliver preemptive strikes to create an environment permissive for early infection. Front Cell Infect Microbiol. 2011;1:26.
Cherkasov A, Hsing M, Zoraghi R, Foster LJ, See RH, Stoynov N, Jiang J, Kaur S, Lian T, Jackson L, Gong H, Swayze R, Amandoron E, Hormozdiari F, Dao P, Sahinalp C, Santos-Filho O, Axerio-Cilies P, Byler K, McMaster WR, Brunham RC, Finlay BB, Reiner NE. Mapping the protein interaction network in methicillin-resistant Staphylococcus aureus. J Proteome Res. 2011 Mar 4;10(3):1139-50.
Silverman JM, Reiner NE. Exosomes and other microvesicles in infection biology: organelles with unanticipated phenotypes. Cell Microbiol. 2011 Jan;13(1):1-9.
Silverman JM, Clos J, Horakova E, Wang AY, Wiesgigl M, Kelly I, Lynn MA, McMaster WR, Foster LJ, Levings MK, Reiner NE. Leishmania exosomes modulate innate and adaptive immune responses through effects on monocytes and dendritic cells. J Immunol. 2010 Nov 1;185(9):5011-22.
Zoraghi R, See RH, Gong H, Lian T, Swayze R, Finlay BB, Brunham RC, McMaster WR, Reiner NE. Functional analysis, overexpression, and kinetic characterization of pyruvate kinase from methicillin-resistant Staphylococcus aureus. Biochemistry. 2010 Sep 7;49(35):7733-47.
Silverman JM, Clos J, de’Oliveira CC, Shirvani O, Fang Y, Wang C, Foster LJ, Reiner NE. An exosome-based secretion pathway is responsible for protein export from Leishmania and communication with macrophages. J Cell Sci. 2010 Mar 15;123(Pt 6):842-52.
Reiner NE. Methods in molecular biology. Macrophages and dendritic cells. Methods and protocols. Preface. Methods Mol Biol. 2009;531:v-vi.
Lee JS, Reiner NE. Stable lentiviral vector-mediated gene silencing in human monocytic cell lines. Methods Mol Biol. 2009;531:287-300.
Moeenrezakhanlou A, Shephard L, Lam L, Reiner NE. Myeloid cell differentiation in response to calcitriol for expression CD11b and CD14 is regulated by myeloid zinc finger-1 protein downstream of phosphatidylinositol 3-kinase. J Leukoc Biol. 2008 Aug;84(2):519-28.
Moeenrezakhanlou A, Nandan D, Reiner NE. Identification of a calcitriol-regulated Sp-1 site in the promoter of human CD14 using a combined western blotting electrophoresis mobility shift assay (WEMSA). Biol Proced Online. 2008 Feb 17;10:29-35.
Silverman JM, Chan SK, Robinson DP, Dwyer DM, Nandan D, Foster LJ, Reiner NE. Proteomic analysis of the secretome of Leishmania donovani. Genome Biol. 2008;9(2):R35.
Hughes PJ, Lee JS, Reiner NE, Brown G. The vitamin D receptor-mediated activation of phosphatidylinositol 3-kinase (PI3Kalpha) plays a role in the 1alpha,25-dihydroxyvitamin D3-stimulated increase in steroid sulphatase activity in myeloid leukaemic cell lines. J Cell Biochem. 2008 Apr 1;103(5):1551-72.