Stephen Wikel

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Stephen Wikel
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Academic Appointments
Appointment Organization
Professor Pathology
Senior Scientist, Center for Tropical Diseases, Biodefense and Emerging Infectious Diseases Pathology
Professional Education
Degree Institution Field of Study Graduation Year
M.Sc. Vanderbilt University Biology (parasitology) 1973
B.A. Shippensburg State College Biology and Chemistry 1967
Ph.D. University of Saskatchewan Veterinary Microbiology -
Honors
Title Organization Year(s)
Outstanding Teaching Award, Schools of Medicine and Dental Medicine, Health Careers Opportunity Prog University of Connecticut Health Center 2006
Jesse S. Heiges Distinguished Alumnus Award Shippensburg University 2001
Recipient of Recognition Award of the Southwestern Branch Entomological Society of America 1994
Featured speaker, Higher Education Day State Capitol of Oklahoma for Chancellor 1992
Awarded McMaster Fellowship Government of Australia, 1990
Named Chester Fritz Distinguished Professor of the University University of North Dakota 1987
Outstanding Teaching Award, School of Medicine University of North Dakota 1987
Recipient of Sigma Xi Faculty Award for Outstanding Scientific Research University of North Dakota 1986
Recipient of Golden Apple Teaching Award American Medical Student Association 1986
Recipient of Sigma Xi Faculty Award for Outstanding Scientific Research University of North Dakota 1986
Professional Affiliations
Society Year(s)
American Association of Veterinary Parasitologists -
American Society of Parasitologists -
Society for Vector Ecology -
Entomological Society of America -
American Society for Microbiology -
American Association of Immunologists -
American Society of Tropical Medicine and Hygiene -
Acarological Society of America -
Research Interests

Emerging and re-emerging diseases transmitted by blood feeding arthropods are significant global public health problems. A major focus of my research is characterization of the complex cellular and molecular immunology of the tick-hostpathogen interface. During the course of blood feeding, ticks introduce pharmacologically active molecules into the host that are essential for both obtaining a blood meal and for successful transmission of infectious agents. Some of these molecules stimulate host innate and specific acquired immune responses that induce resistance to tick feeding. In turn, ticks have developed immunomodulatory countermeasures, which suppress or deviate host innate and specific acquired immune responses. Interactions between host immunity and tick mediated immunomodulation are central to successful tick feeding and disease transmission. Efforts are directed toward the elucidation of the cellular and molecular interactions that occur at the tick-host-pathogen interface. Immunomodulatory proteins in tick saliva are being isolated, characterized, and the genes encoding those molecules are being cloned and expressed. The roles and interactions of those molecules are being studied.

In addition to characterizing the fundamental immunological aspects of these interactions, a combination of genomic and proteomic approaches are being used to identify relevant salivary gland derived proteins. A goal of this research is to develop a novel "vector-blocking" vaccine, which will target those molecules introduced by the tick which are essential for successful feeding and transmission of infectious agents. This strategy is designed to circumvent the need to develop vaccines for each individual tickborne pathogen. Similar approaches are now being applied in this laboratory to the study of the medically important mosquito, Aedes aegypti. Not only do mosquitoes induce host immune responses, but bites by some mosquito species are known to reduce host immune defenses. Characterizing those responses and the molecules responsible for them is a primary focus of this research program. Utilizing an understanding of the complex interactions at the tick and mosquitohost interfaces allows us to now incorporate into these associations vector-borne spirochetes, rickettsiae and arboviruses. Focused systems biology approaches are being developed and utilized to characterize at the molecular level the interplay among ticks and mosquitoes and their hosts and the pathogens transmitted by these arthropods of medical and veterinary public health importance.

Selected Publications
  1. Krause, P.J., Grant-Kels, J.M., Tahan, S.R., Dardick, K.R., Alarcon-Chaidez, F., Bouchard, K., Visini, C., Deriso, C., Foppa, I.M. and Wikel, S.K. Dermatologic changes induced by repeated Ixodes scapularis bites and implications for prevention of tick-borne infection. Vector-Borne and Zoonotic Diseases (In press).
  2. Boppana, V.D., Thangamani, S., Adler, A.J. and Wikel, S.K. SAAG-4 is a novel mosquito salivary protein that programs host CD4+ T cells to express IL-4. Parasite Immunology 31:287-295.
  3. Alarcon-Chaidez, F.J., Boppana, V.D., Hagymasi, A.T., Adler, A.J. and Wikel, S.K.A novel sphingomyelinase-like enzyme present in tick saliva drives host CD4+ T cells to express IL-4. Parasite Immunology 31:210-219.
  4. Brossard, M and Wikel, S.K. Tick immunobiology. In, Ticks: Biology, Disease and Control. Bowman, A.S. and Nuttall, P.A. (Eds). Cambridge University Press, Cambridge, U.K. pp. 186-204.
  5. Ribeiro, J.M.C., Arca, B., Lombardo, F., Calvo, E., Phan, V.M., Chandra, P.K. and Wikel, S.K. An annotated catalogue of salivary gland transcripts in the adult female mosquito, Aedes aegypti. BMC Genomics 8:6 doi:10.1186/1471- 2164-8-6 (27 pages).
  6. Alarcon-Chaidez, F.J., Sun, J., and Wikel, S.K. Transcriptome analysis of thesalivary glands of the tick Dermacentor andersoni Stiles (Acari: Ixodidae). Insect Biochemistry and Molecular Biology 37:48-71.
  7. Geraci, N.S., Johnston, J.S., Robinson, J.P., Wikel, S.K. and Hill, C.A. Variation of genome size of argasid and ixodid ticks. Insect Biochemistry and Molecular Biology 37:399-408.
  8. Müller-Doblies, U.U., S.S. Maxwell, Boppana, V.D., Mihalyo, M.A., McSorley, S.J., Vella, A.T., Adler, A.J. and Wikel, S.K. Feeding by the tick, Ixodes scapularis, causes CD4+ T-cells responding to cognate antigen to develop capacity to express interleukin-4. Parasite Immunology 29:485-499.
  9. Van Zee, J.P., Geraci, N.S., Guerrero, F.D., Wikel, S.K., Stuart, J.J., Nene, V.M. and Hill, C.A. Looking to the future of tick genomics: Insights from the Ixodes genome project. International Journal for Parasitology 37:1297-1305.
  10. Mukherjee, A.K., Sollod, B.L., Wikel, S.K. and King, G.F. Orally active acaricidal peptide toxins from the venom of the Australia funnel-web spider. Toxicon 47:182-187.
  11. Ribeiro, J., Alarcon-Chaidez, F., Francischetti, I.M.B., Mans, B., Mather, T.N., Valenzuela, J.G. and Wikel, S.K. An annotated catalog of salivary gland transcripts from Ixodes scapularis ticks. Insect Biochemistry and MolecularBiology 36:111-129.
  12. Wikel, S.K. Cellular and molecular immune mechanisms at the host - blood feeding arthropod - pathogen interface. Parasite Immunology 28:258-259.
  13. Krause, P.J., Foley, D.J., Burke, G.S., Christianson, D., Closter, L., Spielman, A., Foppa, I., Ryan, R., Baute, P., Miller, J., Wikel, S., Tomas, P., Dias, F., George, T., Pollack, R. and Telford, S. III. Reinfection and relapse in early Lyme disease. American Journal of Tropical Medicine and Hygiene 75:1090-1094.
  14. Alarcon-Chaidez, F., Ryan, R., Wikel, S., Dardick, K., Lawler, C., Foppa, I., Tomas, P., Cushman, A., Hsieh, A., Spielman, A., Bouchard, K., Dias, F., Aslanzadeh, J. and Krause, P. Confirmation of tick bite by detecting antibody to Ixodes calreticulin salivary protein. Clinical and Vaccine Immunology 13:1217-1222.
  15. Chandra, P.K. and Wikel, S.K. Analyzing ligation mixtures using a PCR based method. Biological Procedures Online 7:93-100.
  16. Burke, G., Wikel, S.K., Spielman, A., Pollack, R., McKay, K., Krause, P.J. and the tickborne disease study group. Cutaneous tick hypersensitivity in humans is associated with decreased Lyme disease risk. Emerging Infectious Diseases 11:36-41.
  17. Rajan, T.V., Hein, M., Porte, P. and Wikel, S.K. A double blinded, placebo controlled trial of garlic as a mosquito repellant: a preliminary study. Medical and Veterinary Entomology 19:84-89.
  18. Maxwell, S.S., Stoklasek, T.A., Dash, Y., Macaluso, K.R. and Wikel, S.K. Tick modulation of the in-vitro expression of adhesion molecules by skin-derived endothelial cells. Annals of Tropical Medicine and Parasitology 99:661-672.
  19. Boppana, D.K.V., Wikel, S.K., Raj, D., Manohar, M. and John, L. Cellular infiltration at skin lesion and draining lymph nodes of sheep infested with adult Hyalomma anatolicum anatolicum ticks. Parasitology 131:657-667.
  20. Dash, Y., Maxwell, S.S., Rajan, T.V. and Wikel, S.K. Tick induced murine extramedullary erythropoiesis. Annals of Tropical Medicine and Parasitology 99:519-532.
  21. Boppana, D.K.V., Raj, D., John, L., Wikel, S.K., Latha, B.R. and Gomathinayagam, S. In vivo immunomodulatory effects of ixodid ticks on ovine circulating T and B-lymphocytes. Parasite Immunology 26:83-93.
  22. Wyzga, N., Varghese, S., Wikel, S., Canalis, E. and Sylvester, F.A. Effects of activated T cells on osteoclastogenesis depend on how they are activated. Bone 35:614-620.
  23. Alarcon-Chaidez, F.J., Müller-Doblies, U. and Wikel, S.K. Characterization of a recombinant immunomodulatory protein from the salivary glands of Dermacentor andersoni. Parasite Immunology 25:6977.
  24. Anderson, J.F., Main, A.J., Andreadis, T.G., Wikel, S.K. and Vossbrinck, C.R. Transstadial transmission of West Nile virus by three species of ixodid ticks (Acari: Ixodidae). Journal of Medical Entomology 40:528-533.
  25. Clawson, M.L., Paciorkowski, N., Rajan, T.V., La Vake, C., Pope, C., La Vake, M., Wikel, S.K., Krause, P.J., and Radolf, J.D. Cellular immunity, but not IFN-γ, is essential for resolution of Babesia microti infection in BALB/c mice. Infection and Immunity 70:5304-5306.
  26. Hefty, P.S., Jolliff, S.E., Caimano, M.J., Wikel, S.K., and Akins, D.R. Changes in the temporal and spatial patterns of outer surface lipoprotein expression generates population heterogeneity and antigenic diversity in Borrelia burgdorferi, the Lyme disease spirochete. Infection and Immunity 70:3468-3478.
  27. Roberts, D.M., Caimano, M., McDowell, J., Theisen, M., Holm, A., Orff, E., Nelson, D.,Wikel, S., Radolf, J. And Marconi, R.T. Environmental regulation and differential production of members of the Bdr protein family of Borrelia burgdorferi. Infection and Immunity 70:7033-7041.
  28. Hefty, P.S., Brooks, C.S., Jett, A.M., White, G.L., Wikel, S.K., Kennedy, R.C. and Akins, D.R. The OspE-related, OspF-related and Elp lipoproteins are immunogenic in baboons experimentally infected with Borrelia burgdorferi and in human Lyme disease patients. Journal of Clinical Microbiology 40:4256-4265.
  29. Hefty, P.S., Jolliff, S.E., Caimano, M.J., Radolf, J.D. and Akins, D.R. Regulation of the OspE-related, OspF-related, and Elp lipoproteins of Borrelia burgdorferi strain 297 by mammalia host-specific signals. Infection and Immunity 69:3618-3627.
  30. Macaluso, K.R. and Wikel, S.K. Dermacentor andersoni: effects of repeated infestations on lymphocyte proliferation, cytokine production, and adhesion molecule expression by BALB/c mice. Annals of Tropical Medicine and Parasitology 95:413-427.
  31. Bergman, D.K., Palmer, M.J., Caimano, M.J., Radolf, J.D. and Wikel, S.K. Isolation and molecular cloning of a secreted immunosuppressant protein from Dermacentor andersoni salivary gland. Journal of Parasitology 86:516-525.
  32. Schoeler, G.B., Manweiler, S.A. and Wikel, S.K. Cytokine responses of C3H/HeN mice infested with either Ixodes scapularis or Ixodes pacificus nymphs. Parasite Immunology 22:31-40.
  33. Yang, X., Popova, T.G., Hagman, K.E., Wikel, S.K., Schoeler, G.B., Caimano, M.J., Radolf, J.D., and Norgard, M.V. Identification, characterization, and expression of three new members of the Borrelia burgdorferi Mlp (2.9) lipoprotein gene family. Infection and Immunity 67:6008-6018.
  34. Hagman, K.E., Yang, X., Wikel, S.K., Schoeler, G.B., Caimano, M.J., Radolf, J.D. and Norgard, M.V. Decorin-binding protein A (DbpA) of Borrelia burgdorferi is not protective when mice are challenged via tick infestation and correlates with the lack of DbpA expression by B. burgdorferi in ticks. Infection and Immunity 68:4759-4764.
  35. Yang, X., Goldberg, M.S., Popova, T., Schoeler, G.B., Wikel, S.K., Hagman, K.E. and Norgard, M.V. Interdependence of environmental factors influencing reciprocal patterns of gene expression in virulent Borrelia burgdorferi. Molecular Microbiology 37:1470-1479.
  36. Schoeler, G.B., Manweiler, S.A., Bergman, D.K. and Wikel, S.K. Influence of repeated infestations with pathogen-free Ixodes scapularis (Acari: Ixodidae) on in vitro lymphocyte proliferative responses of C3H/HeN mice. Journal of Medical Entomology 37:885-892.
  37. Schoeler, G.B., Bergman, D.K., Manweiler, S.A. and Wikel, S.K. Influence of soluble proteins from the salivary glands of ixodid ticks on the in-vitro proliferative responses of lymphocytes from BALB/c and C3H/HeN mice. Annals of Tropical Medicine and Parasitology 94:507-518.
  38. Bergman, D.K., Ramachandra, R.N. and Wikel, S.K. Characterization of an immunosuppressant protein from tick, Dermacentor andersoni (Acari: Ixodidae), salivary glands. Journal of Medical Entomology 35:505-509.
  39. Schoeler, G.B., Manweiler, S.A. and Wikel, S.K. Ixodes scapularis: effects of repeated infestations with pathogen-free nymphs on macrophage and T lymphocyte cytokine responses of BALB/c and C3H/HeN mice. Experimental Parasitology 92:239-248.
  40. Wikel, S.K. Tick modulation of host immunity: An important factor in pathogen transmission. International Journal for Parasitology 29:851-859.
  41. Brossard, M. and Wikel, S.K. Immunology of tick-host interactions. Medical and Veterinary Entomology 11:270-276.
  42. Wikel, S.K., Ramachandra, R.N., Bergman, D.K., Burkot, T.R. and Piesman, J. Infestation with pathogen-free nymphs of the tick, Ixodes scapularis, induces host resistance to tick transmission of Borrelia burgdorferi. Infection and Immunity 65: 335-338.
  43. Wikel, S.K. Tick modulation of host cytokines. Experimental Parasitology 84:304-309.
  44. Ramachandra, R.N. and Wikel, S.K. Effects of Dermacentor andersoni (Acari:Ixodidae) salivary gland extracts on Bos indicus and Bos taurus lymphocytes and macrophages: in vitro cytokine elaboration and lymphocyte blastogenesis. Journal of Medical Entomology 32:338-345.
  45. Bergman, D.K., Ramachandra, R.N. and Wikel, S.K. Dermacentor andersoni: salivary gland proteins suppressing T-lymphocyte responses to concanavalin A in vitro. Experimental Parasitology 81:262-271.
  46. Wikel, S.K., Ramachandra, R.N. and Bergman, D.K. Tick induced modulation of the host immune response. International Journal for Parasitology 24:59-66.
  47. Ramachandra, R.N. and Wikel, S.K. Effect of Borrelia burgdorferi strain 297 on peritoneal macrophages of different strains of mice: elaboration of tumor necrosis factor alpha and interleukin-1. Immunology and Infectious Diseases 3:203-207.
  48. Whelen, A.C. and Wikel, S.K. Acquired resistance of guinea pigs to Dermacentor andersoni mediated by humoral factors. Journal of Parasitology 79:908-912.
  49. Ramachandra, R.N., Dalton, D.A. and Wikel, S.K. Antibody and cytokine responses in mice experimentally infected with Borrelia burgdorferi strain 297. Immunology and Infectious Diseases 3:299-308.
  50. Ramachandra, R.N. and Wikel, S.K. 1992. Modulation of host immune responses by ticks (Acari: Ixodidae): impact of salivary gland extracts on host macrophage and lymphocyte cytokine production. Journal of Medical Entomology 29:818-826.
  51. Wikel, S.K., Ramachandra, R.N. and Bergman, D.K. Novel approaches in vector control. Immunological strategies for suppression of vector arthropods. Journal of Vector Ecology 17:10-19.
  52. Ratzlaff, R.E. and Wikel, S.K. Polyplax serrata: characterization of murine immunity and immunization against a solenophagous louse. Journal of Medical Entomology 27:1002-1007.
  53. Wikel, S.K. Immune responses to Psoroptes cuniculi (Acari: Psoroptidae)infestation: Immunoblotting identification of mite antigens. Medical Science Research 17:455-456.
  54. Wikel, S.K., DeVaney, J.A. and Augustine, P.C. Host immune response to northern fowl mite: immunoblot and lectin blot identification of mite antigens. Avian Diseases 33:668-675.
  55. Wikel, S.K. Immunological control of hematophagous arthropod vectors: utilization of novel antigens. Veterinary Parasitology 29:235-264.
  56. Wright, S.M., Wrenn, W.J. and Wikel, S.K. Host immune responsiveness to the chigger, Eutrombicula cinnabaris. Annals of Tropical Medicine and Parasitology 82:283-293.
  57. Wikel, S.K., Olson, F.W. Jr and Richardson, L.K. Immunization induced resistance to Amblyomma americanum infestation. Medical Science Research 15:543-544.
  58. Wikel, S.K. and Whelen,A.C. Ixodid tick-host immune interactions. Identification and characterization of relevant antigens and tick induced host immunosuppression. Veterinary Parasitology 20:149-174.
  59. Whelen, A.C., Richardson, L.K. and Wikel, S.K. Dot-ELISA assessment of guinea pig antibody responses to repeated Dermacentor andersoni infestations. Journal of Parasitology 72:155-162.
  60. Wikel, S.K., Howard, V.M. and Olson, F.W. Jr. Immunological studies of ixodid tick-host interaction: analysis of immunogens. Journal of Toxicology, Toxin Reviews 5:145-160.
  61. George, J.E., Osburn, R.L. and Wikel, S.K. Acquisition and expression of resistance by Bos indicus and Bos indicus x Bos taurus calves to Amblyomma americanum infestation. Journal of Parasitology 71:174-182.
  62. Wikel, S.K. Effects of tick infestation on the plaque-forming cell response to a thymic dependent antigen. Annals of Tropical Medicine and Parasitology 79:195-198.
  63. Wikel, S.K. Resistance to ixodid tick infestation induced by administration of tick tissue culture cells. Annals of Tropical Medicine and Parasitology 79:513-518.
  64. Wikel, S.K. Immunomodulation of host responses to ectoparasite infestation. Veterinary Parasitology 14:321-339.
  65. Whelen, A.C., Richardson, L.K. and Wikel, S.K. Ixodid tick antigens recognized by the infested host: immunoblotting studies. Medical Science Research 12:910-911.
  66. Wikel, S.K. 1982. Histamine content of tick attachment sites and the effects of H1 and H2 histamine antagonists on the expression of resistance. Annals of Tropical Medicine and Parasitology 76:179-185.
  67. Wikel, S.K. and Osburn, R.L. Bovine immune response to defined low level infestations with the ixodid tick, Dermacentor andersoni (Acari: Ixodidae). Annals of Tropical Medicine and Parasitology 76:405-414.
  68. Wikel, S.K. Influence of Dermacentor andersoni infestation on lymphocyte responsiveness to mitogens. Annals of Tropical Medicine and Parasitology 76:627-632.
  69. Wikel, S.K. The induction of host resistance to tick infestation with a salivary gland antigen. American Journal of Tropical Medicine and Hygiene 30:284-288.
  70. Wikel, S.K. Host resistance to tick-borne pathogens by virtue of resistance to tick infestation. Annals of Tropical Medicine and Parasitology 74:103-104.
  71. Portis, J.L., Wikel, S.K. and McAtee, F.J. A simplified rapid method for the purification of glomeruli. Journal of Clinical Pathology 32:406-409.
  72. Allen, J.R., Khalil, H.M. and Wikel, S.K. Langerhans cells trap tick salivary gland antigens in tick resistant guinea pigs. Journal of Immunology 122:563-565.
  73. Bell, J.F., Stewart, S.J. and Wikel, S.K. Resistance to tick-borne Francisella tularensis by tick-sensitized rabbits: allergic klendusity. American Journal of Tropical Medicine and Hygiene 28:876-880.
  74. Wikel, S.K. Acquired resistance to ticks. Expression of resistance by C4 deficient guinea pigs. American Journal of Tropical Medicine and Hygiene 28:586-590.
  75. Wikel, S.K., Graham, J.E. and Allen, J.R. Acquired resistance to ticks. IV. Skin reactivity and in vitro lymphocyte responsiveness to salivary gland antigen. Immunology 34:257-263.
  76. Bell, J.F., Wikel, S.K., Hawkins, W.W. and Owens, C.R. Enigmatic resistance of sheep (Ovis aries) to infection by virulent Francisella tularensis. Canadian Journal of Comparative Medicine 42:310-315.
  77. Wikel, S.K. and Allen, J.R. Acquired resistance to ticks. III. Cobra venom factor and the resistance response. Immunology 32:457-465.
  78. Wikel, S.K. and Allen, J.R. Acquired resistance to ticks. I. Passive transfer of resistance. Immunology 30:311-316.
  79. Wikel, S.K. and Allen, J.R. Acquired resistance to ticks. II. Effects of cyclophosphamide on resistance. Immunology 30:479-484.
  80. Bogitsh, B.J. and Wikel, S.K. Schistosoma mansoni: fine structure of the penetration apparatus and epidermis of the miracidium. Experimental Parasitology 36:342-354.
  81. Colley, D.G. and Wikel, S.K. Schistosoma mansoni: simplified method for the production of schistosomules. Experimental Parasitology 35:44-51
  82. Bogitsh, B.J. and Wikel, S.K. Schistosoma mansoni: ultrastructural observations on the small intestine of the murine host. Experimental Parasitology 35:68-79.
  83. Colley, D.G., Katz, S.P. and Wikel, S.K. Schistosomiasis: an experimental model for the study of immunopathologic mechanisms which involve eosinophils. Advances in the Biosciences 12:653-664.

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