Faculty
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Yongqun “Oliver” He |
Brucella-macrophage interactions, vaccine development, and bioinformatics
Brucella species are gram-negative, facultative intracellular bacteria that cause zoonotic brucellosis in humans and many domestic and wild life animals. Brucella virulence relies on its ability to survive and replicate within vacuolar phagocytic compartments of macrophages. Brucella lipopolysaccharide (LPS) is a virulence factor. Smooth B. abortus, B. melitensis, and B. suis are virulent while their corresponding rough strains, which are deficient in the LPS O-side chain (or O antigen), are attenuated or avirulent. Our current research addresses the specific roles of Brucella LPS and O antigen in Brucella pathogenesis and in the mechanisms of survival and replication inside macrophages by smooth, but not rough, Brucella strains. While smooth virulent Brucella strains inhibit macrophage cell death, many rough attenuated Brucella strains induce programmed macrophage death. We use microarrays and immunological approaches to analyze macrophage gene expression profiles and genes involved in the programmed cell death in responses to smooth virulent and rough attenuated Brucella infections.
Another Brucella research interest is the development of Brucella subunit vaccines using advanced reverse vaccinology and adjuvant technologies. The cattle Brucella vaccine RB51 has greatly enhanced efforts to eradicate brucellosis in the USA. Currently there exists no effective and safe human Brucella vaccine. A better understanding of Brucella pathogenesis and the host immune response will allow rational design of safe and effective vaccines against brucellosis. Reverse vaccinology makes it possible to design vaccines starting from analyzing existing genome information. We are interested in predicting protective antigens and peptides using reserve vaccinology and developing a human Brucella vaccine using a vaccine adjuvant(s) that stimulates strong cell-mediated immunity.
A second major research thrust in this laboratory is bioinformatics and computational biology. We have developed web-based databases and analysis systems to study host-pathogen interactions and vaccines against infectious diseases. We are interested in analyzing biological networks (e.g., apoptosis) by Bayesian network modeling and literature mining. We also have interest in biomedical ontology research including the application of biomedical ontology to data integration and literature mining. These bioinformatics approaches have been explored to study Brucella and other infectious pathogens.
Selected Publications:
Xiang Z, Todd T, Ku KP, Kovacic BL, Larson CB, Chen F, Hodges AP, Tian Y, Olenzek EA, Zhao B, Colby LA, Rush HG, Gilsdorf JR, Jourdian GW, He Y. VIOLIN: Vaccine Investigation and Online Information Network. Nucleic Acids Research. 2008, Vol. 36, Database issue D923-D928.
Xiang Z, Minter RM, Bi X, Woolf PJ, He Y. miniTUBA: medical inference by network integration of temporal data using Bayesian analysis. Bioinformatics. 2007 Sep 15;23(18):2423-32.
Xiang Z, Tian Y, He Y. PHIDIAS: a pathogen-host interaction data integration and analysis system. Genome Biology. 2007 Jul 30;8(7):R150.
Xiang Z, Qin ZS, He Y. CRCView: A web server for analyzing and visualizing microarray gene expression data using model-based clustering. Bioinformatics. 2007 Jul 15;23(14):1843-5.
He Y, Rush HG, Liepman RS, Xiang Z, Colby LA. Pathobiology and management of laboratory rodents administered CDC Category A agents. Comparative Medicine. 2007. Feb;57(1):18-32.
He Y, Reichow S, Ramamoorthy S, Ding X, Lathigra R, Craig JC, Sobral BW, Schurig GG, Sriranganathan N, Boyle SM. Brucella melitensis triggers time-dependent modulation of apoptosis and down-regulation of mitochondria-associated gene expression in mouse macrophages. Infection and Immunity. 2006 Sep;74(9):5035-46.
Xiang Z, Zheng W, He Y. BBP: Brucella genome annotation with literature mining and curation. BMC Bioinformatics. 2006 Jul 16;7(1):347.
He Y, Vines RR, Wattam AR, Abramochkin GV, Dickerman AW, Eckart JD, Sobral BW. PIML: The Pathogen Information Markup Language. Bioinformatics. 2005;21(1):116-21.
He Y, Vemulapalli R, Schurig GG. Recombinant Ochrobactrum anthropi expressing Brucella Cu/Zn-superoxide dismutase protects mice against B. abortus infection only after switching immune responses to Th1 type. Infection and Immunity, 2002, 70(5): 2535-2543.
He Y, Vemulapalli R, Zeytun A, Schurig GG. Induction of specific cytotoxic lymphocytes in mice vaccinated with Brucella abortus RB51. Infection and Immunit. 2001, 69(9): 5502-5508.
