Postdoctoral Position Available

Victor Boyartchuk, Ph.D.

Academic Role: Assistant Professor

Faculty Appointment(s) In:
   Molecular Genetics and Microbiology
   Program in Gene Function and Expression

Other Affiliation(s):
   Center for AIDS Research
   Interdisciplinary Graduate Program
   Program in Immunology and Virology

Studies of the Genetic Factors Controlling Susceptibility to Infectious Diseases using Animal Model Systems

Innate immunity plays a critical role in the host's initial defense against infectious agents. My lab is interested in investigating the genetic basis that underlies differences in susceptibility to infectious diseases. Towards this goal, we are identifying and characterizing the variability in host genes which directly contribute to disease susceptibility. Analyzing the functional consequences of such polymorphisms will allow us to understand more fully the workings of the immune system.

Studies using inbred mouse strains have revealed a number of genetic differences in strain-specific immune responses to infectious diseases. One pathogen eliciting such a differential response is Listeria monocytogenes, a Gram positive facultative intracellular bacterium. Resistance to Listeria infection requires the participation of virtually all components of innate immunity, making this bacterium an ideal tool for studying innate immune functions. Using genetic analysis of differentially susceptible mouse strains, we have identified two major loci in the mouse genome that are likely to harbor genes controlling the course of Listeria infection. Systematic analysis of the expression of genes contained in these regions has identified several promising candidates. Our current work is directed towards identifying mutations that cause differential expression of these genes, and testing of the nature of their effect of the outcome of the infection.

Differences in host immune function usually result in very pleiotropic effects. Therefore, genes shown to affect susceptibility to one infectious disease are likely to play a role in determining the course of other infections. One of our future goals is to identify and characterize the range of pathogen responses that are controlled by each of the genes we are studying. Ultimately, we hope to apply the knowledge we have gained in our studies of disease susceptibility in animal models to customizing the management and treatment of infections in humans.

Representative Publications

Garifulin, O., Qi, Z., Shen H., Patnala, S., Green, M.R. and Boyartchuk, V. (2007) Irf3 polymorphism alters induction of interferon beta in response to Listeria monocytogenes infection. PLoS Genet., 3: e152.

Chen, Y-W., Klimstra, D.S., Mongeau, M.E., Tatem, J.L., Boyartchuk, V. and Lewis, B.C. (2007) Loss of p53 and Ink4a/Arf cooperate in a cell autonomous fashion to induce metastasis of hepatocellular carcinoma cells. Cancer Res. 67: 7589-7596.

Wang, F., Paradkar, P.N., Custodio, A.O., McVey Ward, D., Fleming, M.D., Campagna, D., Roberts, K.A., Boyartchuk, V., Dietrich, W.F., Kaplan, J. and Andrews, N.C. (2007) Genetic variation in Mon1a affects protein trafficking and modifies macrophage iron loading in mice. Nat. Genetics 39: 1025-1032.

Boyartchuk, V., Rojas, M., Yan, B.S., Jobe, O., Hurt, N., Dorfman, D.M., Higgins, D.E., Dietrich, W.F. and Kramnik, I. (2004) The host resistance locus sst1 controls innate immunity to Listeria monocytogenes infection in immunodeficient mice. J. Immunol. 173: 5112-5120.

Shaw, M.H., Boyartchuk, V., Wong, S., Karaghiosoff, M., Ragimbeau, J., Pellegrini, S., Muller, M., Dietrich, W.F. and Yap, G.S. (2003) A natural mutation in the Tyk2 pseudokinase domain underlies altered susceptibility of B10.Q/J mice to infection and autoimmunity. Proc. Natl. Acad. Sci. USA 100: 11594-11599.

Laprade, L., Boyartchuk, V.L., Dietrich, W.F. and Winston, F. (2002) Spt3 plays opposite roles in filamentous growth in Saccharomyces cerevisiae and Candida albicans and is required for C. albicans virulence. Genetics 161: 509-519.

Boyartchuk, V.L. and Dietrich, W. F. (2002) Genetic dissection of host immune response. Genes and Immunity 3: 119-122.

Kramnik, I. and Boyartchuk, V. (2002) Immunity to intracellular pathogens as a complex genetic trait. Current Opinion in Microbiology 5: 111-117.

Watters, J.W., Dewar, K., Lehoczky, J., Boyartchuk, V. and Dietrich, W.F. (2001) Kif1C, a kinesin-like motor protein, mediates mouse macrophage resistance to anthrax lethal factor. Current Biology 11: 1503-1511.

Boyartchuk, V.L., Broman, K.W., Mosher, R.E., D'Orazio, S.E., Starnbach, M.N., and Dietrich, W.F. (2001) Multigenic control of Listeria monocytogenes susceptibility in mice. Nature Genetics 27: 259-260.

Trueblood, C.E., Boyartchuk, V.L., Picologlou, E.A., Rozema, D., Poulter, C.D., and Rine, J. (2000) The CaaX proteases, Afc1p and Rce1p, have overlapping but distinct substrate specificities. Molecular and Cell Biology 20: 4381-4392.

Boyartchuk, V.L and Rine, J. (1998) Roles of prenyl protein proteases in maturation of Saccharomyces cerevisiae a-factor. Genetics 150: 95-101.

Potential Rotation Projects

1. Analysis of the role of CXCL11 in control of bacterial infections.

CXCL11 is a chemokine that in addition to mediating T cell signaling has demonstrated defensin-like bactericidal activity. Mouse strains that differ in sensitivity to L. monocytogenes infection carry different alleles of CXCL11. The goal of the project is to characterize the role of CXCL11 in the course of L. monocytogenes infection and establish the effect of CXCL11 mutations of the outcome of infection.

2. Analysis of Type I interferon induction by L. monocytogenes.

Intracellular L. monocytogenes is capable of inducing IFNb expression that in turn contributes to suppression of innate immunity. We identified inbred mouse strains that in response to L. monocytogenes infection differ in the degree of IFNb induction. We are currently in the process of evaluating candidate genes that determine these differences. The goal of the project is to evaluate polymorphisms in individual candidate genes identified by a combination of genetic mapping and expression profiling experiments.

Laboratory Personnel

Ryan Casey, Volunteer
Oleg Garifulin, Postdoctoral Fellow
Sujatha Patnala, Research Associate

Academic Background

Victor Boyartchuk received his M.S. in 1989 from the Kiev National University in Kiev, Ukraine, and his Ph.D. in 1998 from the University of California at Berkeley. From 1998 to 2002, he was a post-doctoral fellow in the Department of Genetics at Harvard Medical School, where his work was supported by a fellowship from the Irvington Institute for Immunological Research. Dr. Boyartchuck joined the Program in Gene Function and Expression at the University of Massachusetts Medical School as an Assistant Professor of Molecular Genetics and Microbiology in the spring of 2003.

Office: 523/LRB
Phone: 508-856-4353
E-mail: Victor.Boyartchuk@umassmed.edu
Keywords: Genetic Systems, Animal Models of Disease, Infectious Disease

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Postdoctoral Position Available A postdoctoral position is available to study in this laboratory. Contact Dr. Victor Boyartchuk for additional details.