Assistant Professor of Immunogenetics Veterinary Microbiology & Pathology , WSU ADBF, 3043 Pullman, WA 99164-7040   Phone: 509-335-7106 FAX: 2509-335-8529 Email: cdavies@vetmed.wsu.edu   PhD - 1988, Cornell University, Ithaca, NY RESEARCH INTERESTS: Reproductive Immunology   RESEARCH SUMMARY: A major area of investigation in my laboratory is the expression of major histocompatibility complex (MHC) class I genes by the trophoblast cells of the bovine placenta. MHC class I molecules present peptide antigens to cytotoxic T cells and have a profound effect on maternal immunological recognition of the fetus. From the perspective of the maternal immune system the fetus is a foreign tissue. Consequently, for the fetus to survive it must be protected from the potentially hostile maternal immune system. Two mechanisms for protection of the fetus are down regulation of MHC class I genes in the placenta, and local suppression of the maternal immune response. Cattle are unusual in that during the third trimester of pregnancy they express high levels of MHC class I antigens in certain regions of the placenta. This is apparently biologically significant as recognition of fetal MHC antigens by the maternal immune system, and immunological rejection of the placenta, seem to be required for normal placental separation at parturition. Furthermore, inappropriate MHC class I expression by trophoblast cells early in pregnancy appears to be associated with immune mediated abortion. A major impediment to cattle cloning is that cloning results in a very high rate of early embryonic loss. In recent studies, conducted in collaboration with colleagues at Cornell University, we have shown that the trophoblast cells of cloned bovine embryos express high levels of MHC class I antigens early in pregnancy and that this expression is associated with the formation of T cell nodules in the uterine stroma. We believe that maternal immunological recognition of fetal MHC class I antigens, results in abnormal placental development and early embryonic loss. Long-term objectives of my laboratory include: (1) understanding the reproductive and immunological consequences of MHC gene regulation by trophoblast cells; and (2) understanding the mechanisms of MHC gene regulation in trophoblast cells.   REPRESENTATIVE PUBLICATIONS: Davies, C.J., Antczak, D.F. and Allen, W.R. (1985) Reproduction in mules: Embryo transfer using sterile recipients. Equine Veterinary Journal, Suppl. 3:63­67. Davies, C.J., Joosten, I., Bernoco, D., Arriens, M.A., Bester, J., Ceriotti, G., Ellis, S., Hensen, E.J., Hines, H.C., Horin, P., Kristensen, B., Lewin, H.A., Meggiolaro, D., Morgan, A.L.G., Morita, M., Nilsson, Ph.R., Oliver, R.A., Orlova, A., Østergård, H., Park, C., Schuberth, H.-J. Simon, M., Spooner, R.L. and Stewart, J.A. (1994) Polymorphism of bovine MHC class I genes. Joint report of the Fifth International Bovine Lymphocyte Antigen (BoLA) Workshop, Interlaken, Switzerland, August 1992. European Journal of Immunogenetics 21:239­258. Davies, C.J., Joosten, I., Andersson, L., Arriens, M.A., Bernoco, D., Bissumbhar, B., Byrns, G., van Eijk, M.J.T., Kristensen, B., Lewin, H.A., Mikko, S., Morgan, A.L.G., Muggli-Cockett, N.E., Nilsson, Ph.R., Oliver, R.A., Park, C.A., van der Poel, J.J., Polli, M., Spooner, R.L. and Stewart, J.A. (1994) Polymorphism of bovine MHC class II genes. Joint report of the Fifth International Bovine Lymphocyte Antigen (BoLA) Workshop, Interlaken, Switzerland, 1-August 1992. European Journal of Immunogenetics 21:259­289. Davies, C.J., Anderson, L., Ellis, S.A., Hensen, E.J., Lewin, H.A., Mikko, S., Muggli-Cockett, N.E., van der Poel, J.J. and Russell, G.C. (1997) Nomenclature for factors of the BoLA system, 1996. Report of the ISAG BoLA Nomenclature Committee. Animal Genetics 28:159­168. Davies, C.J., Fisher, P.J. and Schlafer, D.H. (2000) Temporal and regional regulation of major histocompatibility complex class I expression at the bovine uterine/placental interface. Placenta 21:194­202. Schlafer, D.H., Fisher, P.J., and Davies, C.J. (2000) The bovine placenta before and after birth: placental development and function in health and disease. Animal Reproductive Science 60­61:145­160. Hill, J.R., Schlafer, D.H., Fisher, P.J. and Davies, C.J. (2002) Abnormal expression of trophoblast major histocompatibility complex class I antigens in cloned bovine pregnancies is associated with a pronounced endometrial lymphocytic response. Biology of Reproduction 67:55-63. Staska, L.M., McGuire, T.C., Davies, C.J. Lewin, H.A. and Baszler, T.V. (2003) Neospora caninum-infected cattle develop parasite-specific CD4+ cytotoxic T lymphocytes. Infection and Immunity 71:3272-3279. Edwards, J.L., Schrick, F.N., McCracken, M.D., van Amstel, S.R., Hopkins, F.M., Welborn, M.G. and Davies, C.J. (2003) Cloning adult farm animals: A review of the possibilities and problems associated with somatic cell nuclear transfer. American Journal of Reproductive Immunology 50:113-123. Park, Y.H., Joo, Y.S., Park, J.Y., Moon, J.S., Kim, S.H., Kwon, N.H., Ahn, J.S., Davis, W.C. and Davies, C.J. (2004) Characterization of lymphocyte subpopulations and major histocompatibility complex haplotypes of mastitis-resistant and susceptible cows. Journal of Veterinary Science 5:29-39. Koo, H.C., Park, Y.H., Hamilton, M.J., Barrington, G.M., Davies, C.J., Kim, J.B., Dahl, J.L., Waters, W.R. and Davis, W.C. (2004) Analysis of the immune response to M. avium subsp. paratuberculosis in experimentally infected calves. Infection and Immunity 72:6870-6883. Davies, C.J., Hill, J.R., Edwards , J.L., Schrick, F.N., Fisher, P.J., Eldridge, J.A., and Schlafer, D.H. (2004) Major histocompatibility complex antigen expression on the bovine placenta: its relationship to abnormal pregnancies and retained placenta. Animal Reproduction Science 82-83:267-280. Staska, L.M., Davies, C.J., Brown, W.C., McGuire, T.C., Suarez, C.E., Park, J.Y., Mathison, B.A., Abbott, J.R., and Baszler, T.V. (2005) Identification of vaccine candidate peptides in the NcSRS2 surface protein of Neospora caninum by using CD4+ cytotoxic T lymphocytes and gamma interferon-secreting T lymphocytes of infected Holstein cattle. Infection and Immunity 73:1321-1329. Traul, D.L., Bhushan, B., Eldridge, J.A., Crawford, T.B., Li, H. and Davies, C.J. (2005) Characterization of Bison bison major histocompatibility complex class IIa haplotypes. Immunogenetics 57:845-854. Ellis ,S.A., Bontrop, R.E., Antczak, D.F., Ballingall, K., Davies, C.J., Kaufman. J., Kennedy, L.J., Robinson, J., Smith, D.M., Stear, M.J., Stet, R.J., Waller, M.J., Walter, L. and Marsh, S.G. (2006) ISAG/IUIS-VIC Comparative MHC Nomenclature Committee report, 2005. Immunogenetics 57:953-958. Davies, C.J., Eldridge, J.A., Fisher, P.J. and Schlafer, D.H. (2006) Evidence for expression of both classical and non-classical major histocompatibility complex class I genes in bovine trophoblast cells. American Journal of Reproductive Immunology 55:188-200.