Leon Grayfer

Leon Grayfer

Title:
Assistant Professor of Biology
Office:
SEH 5695
Phone: 202-994-8076
Email:
leon_grayfer@gwu.edu

Comparative immunology and antimicrobial defenses of poikilothermic vertebrates

Current Research

Poikilothermic vertebrates such as amphibians possess considerably less efficient adaptive immune responses, as compared to mammals. Thus, these organisms must rely more heavily on the innate arms of their respective immune systems. Notably, macrophage-lineage cells are not only integral to vertebrate innate immune and antimicrobial defenses, but are often also infiltrated by invading infectious agents, resulting in pathogen persistence and dissemination. A great example of this dichotomy is presented in the infection of amphibians by the Frog Virus 3 ranavirus, as distinct lineages of amphibian (Xenopus laevis) macrophages confer susceptibility and resistance to this pathogen. Indeed, the success of any given antimicrobial response often hinges on pertinent macrophage development and functional polarization. Accordingly, the Grayfer lab is interested in elucidating the distinct physiological strategies by which poikilothermic organisms such as amphibians regulate their macrophage ontogeny and antimicrobial defenses.

 

Research questions:

What are the mechanisms governing amphibian (X. laevis) macrophage development?

What growth and activation factors contribute to the observed amphibian macrophage functional heterogeneity?

What are the respective roles of distinct amphibian macrophage lineages in antimicrobial defenses against emerging pathogens such as Frog Virus 3?

 

 

Now recruiting graduate students for Fall 2016 semester start date. Interested students should send an updated curriculum vitae to Dr. Grayfer at leon_grayfer@gwu.edu .

Education

B.Sc., University of Alberta, 2006

Ph.D., University of Alberta, 2011

Post-Doctoral Work: Dept. Microbiology and Immunology, University of Rochester (2011-2015)

Publications

Grayfer L, Edholm ES, Robert J. (2015) Mechanisms of amphibian macrophage development: characterization of the Xenopus laevis colony-stimulating factor-1 receptor. Int J Dev Biol. doi: 10.1387/ijdb.140271jr

Guselnikov SV, Grayfer L, De-Jesús Andino F, Rogozin IB, Robert J, Taranin AV. (2015) Retention of duplicated ITAM-containing transmembrane signaling subunits in the tetraploid amphibian species Xenopus laevis. Dev Comp Immunol. doi: 10.1016/j.dci.2015.07.002

Grayfer L, Robert J. (2015) Distinct functional roles of amphibian (Xenopus laevis) colony-stimulating factor-1- and interleukin-34-derived macrophages. J Leuk Biol. doi: jlb.4AB0315-117RR

Edholm ES, Grayfer L, De-Jesús Andino F, Robert J. (2015) Noncalassical MHC-restricted invariant V6 T cells are critical for efficient early innate antiviral immunity in the amphibian Xenopus laevis. J Immunol 195: 576-86

Grayfer L, De-Jesús Andino F, Robert J. (2015) Prominent amphibian (Xenopus laevis) tadpole type III interferon response to the Frog Virus 3 ranavirus. J Virol 89: 5072-5082.

Robert J, Grayfer L, Edholm ES, Ward B, De-Jesús Andino F. (2014) Inflammation-induced reactivation of the ranavirus Frog Virus 3 in asymptomatyic Xenopus laevis. PLoS One doi: 10.1371/journal.pone.0112904

Grayfer L, Robert J. (2014) Divergent antiviral roles of amphibian (Xenopus laevis) M-CSF- and IL-34-derived macrophages. J Leuk Biol 96: 1143-1153.

Sifkarovski J, Grayfer L, Robert J. (2014) Low dose atrazine exposure compromises Xenopus laevis development and effective immunity against FV3. Dev Comp Immunol 47: 52-58.

Grayfer L, Edholm ES, De-Jesús Andino F, Chinchar VG, Robert J. (2014) Ranavirus host immunity and immune evasion. In: Ranaviruses: lethal pathogens of ectothermic vertebrates. Gray MJ (ed) Springer.

Edholm ES, Grayfer L, Robert J. (2014) Evolutionary conserved nonclassical MHC class Ib-dependent invariant T cells. Cell Mol Life Sci 71: 4763-4780.

Grayfer L, De-Jesús Andino F, Robert J. (2014) The amphibian (Xenopus laevis) type I interferon response to Frog Virus 3: new insight into ranavirus pathogenicity. J Virol 88: 5766-5777

Grayfer L, Hodgkinson JW, Belosevic M. (2013) Antimicrobial responses of teleost phagocytes and innate immune evasion strategies of intracellular bacteria. Dev Comp Immunol 43: 223-242

Edholm ES, Albertorio Saez LM, Gill AL, Gill SR, Grayfer L, Haynes N, et al. (2013) Nonclassical MHC class I-dependent invariant T cells are evolutionarily conserved and prominent from early development in amphibians. Proc Natl Acad Sci USA 110: 14342-14347

Grayfer L, Robert J. (2013) Colony-stimulating factor-1-responsive macrophage precursors reside in the amphibian (Xenopus laevis) bone marrow rather than the hematopoietic sub-capsular liver. J Innate Immun 5: 531-542

Rieger AM, Konowalchuk JD, Grayfer L, Katzenback, B.A., Havixbeck JJ, Belosevic M, Barreda DR. 2012. Fish and mammalian phagocytes differentially regulate pro-inflammatory and homeostatic responses in vivo. PLoS One 7: e47070. (doi: 10.1371/journal.pone.0047070).

Grayfer L, Belosevic M. (2012) Cytokine regulation of teleost inflammatory responses. In: New Advances and Contributions to Fish Biology. Turker, H. (ed). In Tech. ISBN 978-953-51-0909-9.

Grayfer L, De-Jesús Andino F, Chen G, Chinchar GV, Robert J. (2012) Immune evasion strategies of ranaviruses and innate immune responses to these emerging pathogens. Viruses 4: 1075-1092.

Hodgkinson WJ, Ge J, Grayfer L, Belosevic, M. (2012) Analysis of the immune response in infections of goldfish (Carassius auratus L.) with Mycobacterium marinum. Dev Comp Immunol 38: 456-465.

De-Jesús Andino F, Chen G, Li Z, Grayfer L, Robert J. (2012) Susceptibility of Xenopus laevis tadpoles to infection by the ranavirus Frog-Virus 3 correlates with a reduced and delayed innate immune response in comparison with adult frogs. Virology 432: 435-443.

Garcia-Garcia E, Grayfer L, Stafford JL, Belosevic M. (2012) Evidence for the presence of functional lipid rafts in immune cells of ectothermic organisms. Dev Comp Immunol 37: 257-269.

Grayfer L, Belosevic M. (2011) Identification and molecular characterization of the interleukin-10 receptor 1 of the zebrafish (Danio rerio) and the goldfish (Carassius auratus L.). Dev Comp Immunol 36: 408-417.

Grayfer L, Hodgkinson WJ, Belosevic M. (2011) Analysis of the antimicrobial responses of primary phagocytes of the goldfish (Carassius auratus L.) against Mycobacterium marinum. Dev Comp Immunol 35: 1146-1158.

Grayfer L, Hodgkinson WJ, Hitchen JS, Belosevic M. (2010) Characterization and functional analysis of goldfish (Carassius auratus L.) interleukin-10. Mol Immunol 48: 563-571.

Grayfer L, Garcia-Garcia E, Belosevic M. (2010) Comparison of macrophage antimicrobial responses induced by type II interferons of the goldfish (Carassius auratus L.). J Biol Chem 285: 23537-23547.

Abu-Dayyeh I, Ralph B, Grayfer L, Belosevic M, Cousineau B, Olivier, M. (2010) Identification of key cytosolic kinases containing evolutionarily conserved kinase tyrosine-based inhibitory motifs (KTIMs). Dev Comp Immunol 34: 481-484.

Grey CL, Grayfer L, Belosevic M, Chang JP. (2009) Ghrelin stimulation of gonadotropin (LH) release from goldfish pituitary cells: presence of the growth hormone secretagogue receptor (GHSR-1a) and involvement of voltage-sensitive Ca2+ channels. Mol Cell Endocrinol 317: 64-77.

Grayfer L, Belosevic M. (2009) Molecular characterization of novel interferon gamma receptor 1 isoforms in zebrafish (Danio rerio) and goldfish (Carassius auratus L.). Mol Immunol 46: 3050-3059.

Grayfer L, Belosevic M. (2009) Molecular characterization of tumor necrosis factor receptors 1 and 2 of the goldfish (Carassius auratus L.). Mol Immunol 46: 2190-2199.

Grayfer L, Hanington PC, Belosevic M. (2009) Macrophage colony-stimulating factor (CSF-1) induces pro-inflammatory gene expression and enhances antimicrobial responses of goldfish (Carassius auratus L.) macrophages. Fish Shellfish Immunol 26: 406-413.

Grayfer L, Belosevic M. (2009) Molecular characterization, expression and functional analysis of goldfish (Carassius auratus L.) interferon gamma. Dev Comp Immunol 33: 235-246.

Grayfer L, Walsh JG, Belosevic M. (2008) Characterization and functional analysis of goldfish (Carassius auratus L.) tumor necrosis factor-alpha. Dev Comp Immunol 32: 532-543.

Haddad G, Hanington PC, Wilson EC, Grayfer L, Belosevic M. (2008) Molecular and functional characterization of goldfish (Carassius auratus L.) transforming growth factor-beta. Dev Comp Immunol 32: 654-663.

Belosevic M, Haddad G, Walsh JG, Grayfer L, Katzenback BA, Hanington PC, et al. (2008) Innate immunity of fish: Antimicrobial responses of fish macrophages. In: Fish Defenses Volume 1, (Fish Immunology). G Zaccone, MJ Manning, CJ Secombes, BG Kapor (eds.) Science Publishers, Enfield (N.H.). ISBN 978-57808-327-5.