Education

Ph.D. Cornell University

Research interests

Zebrafish as a Model for Infectious Disease: Throughout history infectious diseases have played a major role in the human condition worldwide. Pathogens also have tremendous environmental and economic impact in agriculture and aquaculture. To counter these agents, vaccines, antibiotics, and new intervention strategies are continually being developed. Although these methods have largely proven to be effective as we have sought to keep pace with microbial adaptation and environment-triggered emergence of new diseases, investigation into alternative methods for controlling infectious disease is clearly warranted.

Through our disease studies with zebrafish, we hope to better understand the myriad immune factors that augment, extend, and prolong the immune response to infection. In order to develop more effective vaccines and to understand host response to pathogens, an infectious disease model is essential. In our studies, zebrafish are exposed to bacterial and viral pathogens that are known to cause disease in other fish species that live in similar environments (e.g. temperature, freshwater vs. marine). Once we have identified the bacteria or viruses that cause disease in the zebrafish, we can study host responses to infection and devise methods to boost host immune response.

Characterization of Zebrafish Toll Signal Transduction Pathway: Recent recognition of the intrinsic importance of the innate immune response, in addition to its regulatory role in subsequent adaptive immunity, suggests that this system plays a crucial role in protection against agents of infectious disease. Our goal is to better understand the innate immune response through the Toll signal transduction pathway. Evidence suggests the existence of Toll receptors, described as "pattern recognition receptors," with the ability to detect a variety of indicators of infectious organisms, and which feed into a common activation pathway. Activation of either the invertebrate or vertebrate signaling pathways results in a cascade of events that leads to the subsequent translocation of a transcription factor (Dorsal or NF-kb, respectively) into the nucleus and regulates synthesis of either antimicrobial/antifungal peptides or cytokines. Through molecular dissection of this pathway in the zebrafish, a vertebrate with a less complex immune system than that of mammals, we seek to identify factors that influence regulation of the innate immune response as well as its role in regulating the adaptive immune response. Ultimately, we hope to learn enough about the Toll signaling pathway to begin to develop methods for intervention that can be applied to mammals and other fish species.

Environmental Toxicants and the Immune System: We recently have become interested in the effects of environmental toxicants, such as arsenic, on the host’s ability to fight infection.  In our initial studies, zebrafish were exposed to relatively high levels (50 and 100 uM) of arsenic and have shown that these levels severely compromise the host’s ability to mount an appropriate antiviral immune response.  We have continued these studies with very low levels (2 and 10 ppb) of arsenic – levels that are considered safe in drinking water.  In these studies, the overall innate immune response was dramatically dampened and the zebrafish were unable to contain and combat either bacterial or viral infection.

Publications

• Sullivan, C., J. Charette, J. Catchen, C.R. Lage, G. Giasson, J.H. Postlethwait, P.J. Millard and C.H. Kim. 2009. The gene history of zebrafish tlr4a and tlr4b is predictive of their divergent functions. J. Immunol. 83:5896-908.
• Sullivan, C., and C. H. Kim. 2008. Innate Immune System of the Zebrafish, Danio rerio. In Innate Immunity of Plants, Animals, and Humans. H. Heine, ed. 113 – 133.
• Sullivan, C. and C.H. Kim. 2008. Zebrafish as a model for infectious disease and immune function. Fish Shellfish Immunol. 25:341-50.
• Sullivan, C., J.H. Postlethwait, C.R. Lage, P.J. Millard, and C.H. Kim. 2007. Evidence for Evolving TICAM Function in Vertebrates. J. Immunol. 178:4517-27
• Nayak, A.N, C.R. Lage, and C.H. Kim. 2007. Effects of Low Concentrations of Arsenic on the Innate Immune System of the Zebrafish (Danio rerio). Toxicol. Sci. 98:118-24.
• Lage, C.R., A. Nayak, and C.H. Kim. 2006. Arsenic ecotoxicology and innate immunity. Integr. Comp. Biol. 46: 1040 - 1054
• Millard, P.J., L.E. Bickerstaff, S.E. LaPatra, and C.H. Kim. 2006. Detection of infectious hematopoietic necrosis virus and infectious salmon anemia virus by molecular padlock amplification. J. Fish. Dis. 29:201-213.
• Hermann, A.C. and C.H. Kim. 2005. Effects of arsenic on the zebrafish innate immune system. Mar. Biotechnol. 7:494-505.
• Phelan, P.E., M.T. Mellon, and C.H. Kim. 2005. Functional characterization of full-length TLR3, IRAK-4, and TRAF6 in zebrafish (Danio rerio). Mol. Immunol. 42:1057-1071.
• Phelan, P.E., M.E. Pressley, P.E. Witten, M.T. Mellon, S.L. Blake, and C.H. Kim. 2005. Characterization of snakehead rhabdovirus infection in the zebrafish, Danio rerio. J. Virol. 79:1842-1852.
• Pressley , M.E. , P.E. Phelan, III, P.E. Witten, M.T. Mellon, and C.H. Kim. 2005. Pathogenesis and inflammatory response to Edwardsiella tarda Infection in the zebrafish. Dev. Comp. Immunol. 29:501-513.
• Hermann, A.C, P.J. Millard, S.L. Blake, and C.H. Kim. 2004. Development of a respiratory burst assay using zebrafish kidneys and embryos. J. Immunol. Methods. 292:119-129.
• Alonzo, M., C.H. Kim, M.C. Johnson, M.E. Pressley, and J.C. Leong. 2004. The NV gene of snakehead rhabdovirus (SHRV) is not required for pathogenesis and a heterologous glycoprotein can be incorporated into the SHRV envelope. J. Virol. 78:5875-5882.
• Altmann, S.M., M.T. Mellon, M.C. Johnson, B.H. Paw, N.S. Trede, L.I. Zon and C.H. Kim. 2004. Cloning and characterization of an Mx gene and its corresponding promoter from the zebrafish, Danio rerio. Dev. Comp. Immunol. 28:295-306.
• Paw, B.H, A.J. Davidson, Y. Zhou, L. Rong, S.J. Pratt, C. Lee, N.S. Trede, A. Brownlie, A. Donovan, E.C. Liao, J.M. Ziai, A.H. Drejer, W. Guo, C.H. Kim, B. Gwynn, L.L. Peters, M.N. Chernova, S.L. Alper, A. Zapata, S.N. Wickramasinghe, M.J. Lee, S.E. Lux, A. Fritz, J.H. Postlewait, L.I. Zon. 2003. Cell-specific mitotic defect and dyserythropoiesis associated with erythroid band 3 deficiency. Nat. Genet. 34:59-64.
• Altmann, S.M., M.T. Mellon, D.L. Distel, and C.H. Kim. 2003. Molecular and functional analysis of an interferon gene from the zebrafish, Danio rerio. J. Virol. 77:1992-2002.

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