William C. Davis
- BA: Chico State College, Chico, California (Biology), 1955
- MA: Stanford University, Palo Alto, California (Biology), 1959
- PhD: Stanford University, Palo Alto, California (Medical Microbiology Transplantation Immunology), 1967
Director of the WSU Monoclonal Antibody Center and the Flow Cytometry Facility. The overall program in immunology is focused on analysis of the mechanisms regulating the immune response to infectious agents and derived vaccines. Ongoing studies are focused on: 1) Development and characterization of monoclonal antibodies (mAbs) to leukocyte differentiation molecules, cytokines, chemokines, and their respective receptors that are involved in activation and maturation of naive T- and B-lymphocytes and antigen presenting cells. Characterization of new mAbs involves the use of flow cytometry, molecular techniques, and a web-based taxonomic key program (TKP) vetmed.wsu.edu/tkp. The TKP program is designed to facilitate the comparative analysis of the specificity of mAbs specific for known and new leukocyte differentiation molecules. 2) Determining the factors that modulate uptake, processing, and presentation of exogenous antigens on MHC class I and class II molecules by antigen presenting cells (APC). Studies involve the use of in vitro culture techniques and RT-PCR to study APC activation following antigen uptake and flow cytometry to study the phenotypic changes that occur during the evolution of an immune response from naive T cells to effector and memory T cells. 3) Elucidation of the role of γδT cells in first line of defense in cattle. Current studies are focused on characterizing γδ T cell subpopulations in cattle and determining the factors that regulate activation and function of γδ T cells. The studies involve the use of flow cytometry to isolate cells for in vitro culture and molecular analysis.
The study of mechanisms regulating the immune response to infectious agents and vaccines.
The long term objectives of our research program are to elucidate the mechanisms regulating the immune response to infectious agents and develop protective vaccines. To achieve these objectives, we continue to develop and use monoclonal antibodies and assays to study the immune response in domestic animals with a primary focus on ruminants. M. avium subsp. Paratuberculosis (Map) has been selected as the model pathogen for our investigations because of its economic importance and its potential for providing insight into the mechanisms regulating the immune response to Map and other intracellular pathogens. Map is the causative agent of Johne’s disease (JD) in cattle, a chronic wasting disease of the intestine. It causes significant economic loss to producers, especially the dairy industry, due to increase in forage consumption, decreased milk production and early culling due to poor health of affected animals. There is also a concern that Map is a zoonotic pathogen. Map has been isolated from human patients with Crohn’s disease (CD), a chronic inflammatory disease of the intestine. It is not clear whether Map is the etiologic agent causing Crohn’s disease. However, recent studies on CD and mycobacterial pathogens M. tuberculosis (Mtb) and Map have shown a similarity in the mechanisms of pathogenesis at the cellular and molecular level. The studies have revealed the cross regulation of the immune system by regulatory T cells and effector T cells mediating protective immune responses is dysregulated, giving rise to an imbalance that results in chronic inflammation of target tissues, and in the case of Mtb and Map dysregulation of protective immunity. To extend these observation we developed a bovine cannulated ileum model to conduct studies on the mechanisms of pathogenesis mediated by Map in the natural host, studies that cannot be conducted in humans. The model has offered an opportunity to study the interaction of Map during the early and late stages of infection. We have also developed and used a flow cytometric assay to analyze the immune response to Map and methods to elucidate the functional changes associated with dysregulation of the immune system. Use of these methods in conjunction with development of methods to monitor the intracellular killing of bacteria by cytotoxic T cells have facilitated analysis of the functional activity of cytotoxic T cells responding to Map and derived candidate antigens. Ongoing studies with a mutant of Map, with a deletion in relA, has shown deletion abrogates the capacity of the mutant to establish a persistent infection. Further studies have shown the target of the immune response is directed towards a membrane protein (MMP). Ex vivo studies have shown stimulation with the MMP leads to the development of cytotoxic T cells with the capacity to kill intracellular bacteria. This major finding indicates a peptide based vaccine is possible against a major pathogen. These findings will now be used to advance our studies to the next phase, development and validation of a virus vector containing the gene encoding the MMP as a vaccine for JD.
- Abdellrazeq GS, Elnaggar MM, Bannantine JP, Schneider DA, Souza CD, Hwang J, Mahmoud AHA, Hulubei V, Fry LM, Park KT, Davis WC. (2019) A peptide-based vaccine for Mycobacterium avium subspecies paratuberculosis. Vaccine pii: S0264-410X(19)30504-3. doi: 10.1016/j.vaccine.2019.04.040. [Epub ahead of print] PMID: 31003915 PMCID:
- Hussein HE, Bastos RG, Schneider DA, Johnson WC, Adham FK, Davis WC, Laughery JM, Herndon DR, Alzan HF, Ueti MW, Suarez CE. (2017) The Babesia bovis hap2 gene is not required for blood stage replication, but expressed upon in vitro sexual stage induction. PLoS Negl Trop Dis. 11(10):e0005965. doi: 10.1371/journal.pntd.0005965. eCollection 2017 Oct. PMID: 28985216 PMCID: PMC5646870
- Grandoni F, Elnaggar MM, Abdellrazeq GS, Signorelli F, Fry LM, Marchitelli C, Hulubei V, Khaliel SA, Torky HA, Davis WC. (2017) Characterization of leukocyte subsets in buffalo (Bubalus bubalis) with cross-reactive monoclonal antibodies specific for bovine MHC class I and class II molecules and leukocyte differentiation molecules. Dev Comp Immunol. 74:101-109. doi: 10.1016/j.dci.2017.04.013. Epub 2017 Apr 20. PMID: 28433527 PMCID:
- Elnaggar MM, Abdellrazeq GS, Elsisy A, Mahmoud AH, Shyboub A, Sester M, Khaliel SA, Singh M, Torky HA, Davis WC. (2017) Evaluation of antigen specific interleukin-1beta as a biomarker to detect cattle infected with Mycobacterium bovis Tuberculosis (Edinb). 105:53-59. doi: 10.1016/j.tube.2017.04.009. Epub 2017 Apr 24. PMID: 28610788 PMCID:
- Davis WC, Kuenstner JT, Singh SV (2017) Resolution of Crohn's (Johne's) disease with antibiotics: what are the next steps? Expert Rev Gastroenterol Hepatol. 9, 1-4 PMID: 28276276 PMCID:
- Park KT, Elnaggar MM, Abdellrazeq GS, Bannantine JP, Mack V, Fry LM, Davis WC (2017) Correction: Phenotype and Function of CD209+ Bovine Blood Dendritic Cells, Monocyte-Derived-Dendritic Cells and Monocyte-Derived Macrophages. PLoS One 12(1) PMID: 28122067 PMCID: PMC5266315
- McEntire MC, Wardrop KJ, Davis WC (2017) Comparison of established and novel methods for the detection and enumeration of microparticles in canine stored erythrocyte concentrates for transfusion. Vet Clin Pathol. 46(1), 54-63 PMID: 27935625 PMCID:
- Highland MA, Schneider DA, White SN, Madsen-Bouterse SA, Knowles DP, Davis WC (2016) Differences in leukocyte differentiation molecule abundances on domestic sheep (Ovis aries) and bighorn sheep (Ovis canadensis) neutrophils identified by flow cytometry Comp Immunol Microbiol Infect Dis. 46, 40-6 PMID: 27260809 PMCID:
- Singh SV, Kuenstner JT, Davis WC, Agarwal P, Kumar N, Singh D, Gupta S, Chaubey KK, Kumar A, Misri J, Jayaraman S, Sohal JS, Dhama K (2016) Concurrent Resolution of Chronic Diarrhea Likely Due to Crohn's Disease and Infection with Mycobacterium avium paratuberculosis. Front Med (Lausanne). 3, 49 PMID: 27833911 PMCID: PMC5081375
- Tuo W, Li L, Lv Y, Carrillo J, Brown D, Davis WC, Song J, Zarlenga D, Xiao Z (2016) Abomasal mucosal immune responses of cattle with limited or continuous exposure to pasture-borne gastrointestinal nematode parasite infection. Vet Parasitol. 229, 118-125 PMID: 27809966 PMCID:
- Elnaggar MM, Abdellrazeq GS, Mack V, Fry LM, Davis WC, Park KT (2016) Characterization and use of new monoclonal antibodies to CD11c, CD14, and CD163 to analyze the phenotypic complexity of ruminant monocyte subsets. Vet Immunol Immunopathol. 178, 57-63 PMID: 27496743 PMCID:
- Parasar P, Wilhelm A, Rutigliano HM, Thomas AJ, Teng L, Shi B, Davis WC, Suarez CE, New DD, White KL, Davies CJ (2016) Expression of bovine non-classical major histocompatibility complex class I proteins in mouse P815 and human K562 cells. Res Vet Sci. 107, 161-70 PMID: 27473990 PMCID:
- Abdellrazeq GS, Elnaggar MM, Osman HS, Davis WC, Singh M (2016) Prevalence of Bovine Tuberculosis in Egyptian Cattle and the Standardization of the Interferon-gamma Assay as an Ancillary Test. Transbound Emerg Dis 63(5), 497-507 PMID: 25408173 PMCID: