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Dr. Keith R. Fowke
Associate Professor Department of Medical Microbiology

Degrees:
B.Sc.(H) (Manitoba, 1988), Ph.D. (Manitoba, 1995)

Mailing Address:
Laboratory of Viral Immunology
Department of Medical Microbiology
730 William Avenue, Room 539
Winnipeg, MB R3E 0W3

Tel: (204) 789-3818
Fax: (204) 789-3926
E-mail: fowkekr@cc.umanitoba.ca


Keith received his B.Sc. (H) in Microbiology (1988) and PhD in Medical Microbiology (1995) from the University of Manitoba (UM). He then did a postdoctoral fellowship in cellular immunology with Dr. Gene Shearer at the National Institutes of Health’s National Cancer Institute in Bethesda, Maryland (1995-1999). In 1999 he joined BBI Biotech Research Laboratories, in Gaithersburg Maryland as a project scientist. In October of that year Keith was recruited to the UM’s Department of Medical Microbiology and was promoted, with tenure, in 2004 to Associate Professor. He also has cross appointments with the Dept of Community Health Science (UM), the University of Nairobi and the Public Health Agency of Canada’s National Microbiology Lab. Keith’s laboratory focuses on defining cellular immune mechanisms of the control of, and resistance to, HIV infection. His lab also has in interest in the mechanisms of immune activation that contribute to rapid HIV disease progression. For these projects the laboratory has received local, national and international funding from sources such as the Canadian Institutes for Health Research, American and Canadian Foundations for AIDS Research, the Elizabeth Glaser Foundation for Pediatric AIDS Research and the Bill and Melinda Gates Foundation. Keith’s work has been recognized through the Ken Hughes Investigator Award for Medical Research from the University of Manitoba, the Canadian Institutes for Health Research New Investigator Award (2005-2010) and the 2006 Winnipeg Rh Institute Foundation Award in Health Sciences Research.


The Laboratory of Viral Immunology is a vital, active laboratory focused on training scientists at the M.Sc., Ph.D., or postdoctoral levels through basic studies in the immunobiology of HIV infection. The emphasis in the lab is doing excellent research in an enjoyable environment. To undertake these studies we collaborate extensively with colleagues throughout world including Nairobi, Kenya. Together with our Kenya collaborators we have described a group of commercial sex workers who, although highly exposed to HIV, do not become infected with the virus. The lab also focuses on control of HIV infection observed in populations of Winnipeg-based HIV infected subjects. The Viral Immunology Laboratory is currently focusing in two major areas of research. The first is determining the immunological phenotype and genetic expression of CD4+ T-cells HIV resistance individuals. The second focuses on the role of immune activation, regulatory T cells, T cell memory phenotypes and receptor polymorphisms in HIV disease progression. These studies combine a multidisciplinary approach that, through basic virology, molecular biology and cellular immunology, explore new aspects of HIV immunobiology.

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    2007

  1. McKinnon LR, Ball TB, Wachihi C, McLaren PJ, Waruk JL, Mao X, Ramdahin S, Anzala AO, Kamene J, Luo M, Fowke KR, Plummer FA. Epitop cross-reactivity frequently differs between cntral and effector memory HIV-specific CD8+ T cells. J Immunol. 2007 Mar 15;178(6):3750-6. PMID: 17339472
  2. Negative mucosal synergy between Herpes simplex type 2 and HIV in the female genital tract. Rebbapragada A, Wachihi C, Pettengell C, Sunderji S, Jaoko W, Ball B, Fowke K, MazzulliT, Plummer FA, Kaul R. AIDS. 2007 Mar 12;21(5):589-98. PMID:1731452

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    2006

  3. Alimonti JB, Kimani J, Matu L, Wachihi C, Kaul R, Plummer FA and FOWKE KR. Characterization of CD8+ T cell responses in HIV-1 exposed seronegative commercial sex workers from Nairobi, Kenya. In Press in Immunology and Cell Biology.
  4. Koesters SA, Alimonti JB, Wachichi C, Matu L, Anzala O, Kimani J, Embree JE, Plummer FA and FOWKE KR. IL-7Ra Expression on CD4+ T Lymphocytes Decreases with HIV Disease Progression and Inversely Correlates with Immune Activation. European J. Immunology. 2006. 36:336-44. PMID: 16421946

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  5. 2005

  6. McKinnon LR, Ball TB, Kimani J, Wachihi C, Matu L, Luo M, Embree J, FOWKE KR, Plummer FA. Cross-Clade CD8+ T-Cell Responses With a Preference for the Predominant Circulating Clade. J Acquir Immune Defic Syndr. 2005. 40:245-249. PMID: 16249696
  7. Ao Z, FOWKE KR, Cohen EA, Yao X. Contribution of the C-terminal tri-lysine regions of human immunodeficiency virus type 1 integrase for efficient reverse transcription and viral DNA nuclear import. Retrovirology. 2005, 2:62. PMID: 16232319
  8. Iqbal SM, Ball TB, Kimani J, Kiama P, Thottingal P, Embree J, FOWKE KR, Plummer FA Elevated T cell counts and RANTES expression in the genital mucosa of HIV-resistant Kenyan sex-workers. J Infect Disease. 2005. 192:728-38. PMID: 16088822
  9. Alimonti JB, Koesters SA, Kimani J, Matu L, Wachihi C, Plummer FA and FOWKE KR. CD4+ T cell responses in HIV-exposed seronegative subjects are qualitatively distinct from those in HIV-infected individuals. J Infect Diseases. 2005. 191:20-4. PMID: 15592998

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  10. 2004

  11. Koesters S, Matu L, Kiama P, Anzala O, Embree J, Plummer FA, Kimani J, FOWKE KR. Elevation of immune activation in Kenyan women is associated with alterations in immune function: Implications for vaccine development. J Clinical Immunology. 2004. 24:702-9. PMID: 15622455
  12. Kaul R, Rutherford WJ, Rowland-Jones SL, Kimani J, Onyango JI, FOWKE KR, MacDonald K, Bwayo JJ, McMichael AJ, Plummer FA. Prospective associations of HIV-1 Env specific cytotoxic T lymphocyte responses in highly-exposed, persistently seronegative Kenyan sex workers. AIDS. 2004. 18:2087-9. PMID:15577632
  13. Shi B, Philpott SM, Weiser B, Kuiken C, Brunner C, Fang G, FOWKE KR, Plummer FA, Rowland-Jones S, Bwayo J, Anzala AO, Kimani J, Kaul R, and Burger H. Construction of an infectious HIV-1 molecular clone from a patient with a subtype D/C recombinant virus. AIDS Research and Human Retroviruses. 2004; 20:1015-18. PMID: 15585089
  14. Mayne M, Moffatt T, Kong H, McLaren PJ, FOWKE KR, Becker KG, Namaka M, Schenck A, Bardoni B, Bernstein CN, Melanson M CYFIP2 is highly abundant in CD4+ cells from multiple sclerosis patients and is involved in T cell adhesion. European Journal of Immunology 2004 34:1217-27. PMID: 15048733
  15. Paul J. McLaren, Michael Mayne, Stuart Rosser, Teri Moffatt, Kevin G. Becker, Francis A. Plummer, and Keith R. Fowke
    Antigen-Specific Gene Expression Profiles of Peripheral Blood Mononuclear Cells Do Not Reflect Those of T-Lymphocyte Subsets.2004 Sep;11(5): 977-82.. PMID:15358662

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  16. 2003

  17. Luo M, Kimani J, FOWKE K, Ball B, MacDonald K, Ramdahin S, Ndinya-Achola J, Njenga S, Bwayo JB, Embree J, Plummer FA. Evolutionary implications of current HIV epidemic on the population of Kenya, East Africa: study of population genetics by sequence-based DRB typing. Hum Immunol. 2003; 64:S20.
  18. Alimonti JB*, Ball TB and FOWKE KR. Mechanisms of CD4+ T Lymphocyte Cell Death in HIV/AIDS. J. Gen Virol. 2003; 84: 1649-1661 and JGV Direct on-line publication.| PubMed|

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  19. 2002

  20. Koesters S*, Rutherford WJ, FOWKE KR. Development of a novel allo-independent HIV-1 virus for use in immunoassays. J. Immunol Meth. 264: 69-76, 2002.| PubMed|
  21. 2001

  22. MacDonald KS, Matukas L, Embree JE, FOWKE K, Kimani J, Nagelkerke NJ, Oyugi J, Kiama P, Kaul R, Luscher MA, Rowland-Jones S, Ndinya-Achola J, Ngugi E, Bwayo JJ, Plummer FA. Human leucocyte antigen supertypes and immune susceptibility to HIV-1, implications for vaccine design. Immunol Lett 2001 79:151-7. | PubMed |
  23. Kaul R, Rowland-Jones SL, Kimani J, FOWKE KR, Dong T, Kiama P, Rutherford J, Njagi E, Mwangi F, MacDonald KS, Bwayo JJ, Plummer FA. New insights into HIV-1 specific cytotoxic T-lymphocyte responses in exposed, persistently seronegative Kenyan sex workers. Immunol Lett 2001, 79:3-13. | PubMed |
  24. Kashiwada Y, Chiyo J, Ikeshiro Y, Nagao T, Okabe H, Cosentino LM, FOWKE K, Lee KH. 3,28-Di-O-(dimethylsuccinyl)-betulin isomers as anti-HIV agents. Bioorg Med Chem Lett. 2001,11:183-5. | PubMed |
  25. Kashiwada Y, Yamazaki K, Ikeshiro Y, Yamagishi T, Fujioka T, Mihashi K, Mizuki K, Cosentino LM, FOWKE K, Morris-Natschke SL, Lee KH. Isolation of rhododaurichromanic acid B and the anti-HIV principles rhododaurichromanic acid A and rhododaurichromenic acid from Rhododendron dauricum. Tetrahedron 57 (8): 1559-1563 FEB 18 2001. | PubMed |
  26. Chougnet C, Jankelevich, S, FOWKE KR, Liewehr DJ, Steinberg SM, Mueller BU, Pizzo PA, Yarchoan R, and Shearer GM. Long-term protease inhibitor containing-therapy results in limited improvement in T-cell function but not restoration of interleukin-12 production in pediatric AIDS patients. J Infect Dis. 2001 184:201-5. | PubMed |

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    2000

  27. FOWKE KR, Kaul R, Rosenthal KL, Oyugi J, Kimani J, Rutherford WJ, Nagelkerke NJD, Ball TB, Bwayo J, Simonsen JN, Shearer GM, Plummer FA. HIV-1 specific cellular immune responses among HIV-1 resistant sex workers. Immunology and Cell Biology, 2000, 78:586-95. | PubMed |
  28. Kashiwada, Y, Chiyo J, Ikeshiro Y, Nagao T, Okabe H, Cosentino LM, FOWKE K, Morris-Natschke SL, and Lee KH. Synthesis and anti-HIV activity of 3-alkylamido-3-deoxy-betulinic acid derivatives. Chem Pharm Bull (Tokyo) 2000, 48:1387
    | PubMed |
  29. FOWKE KR, Behnke J, Hanson C, Shea K and Cosentino LM. Apoptosis: A method of evaluating whole blood and peripheral blood mononuclear cell cryopreservation. J. Imm. Methods 2000, 244:139-44. | PubMed |
  30. MacDonald KS, FOWKE KR, Kimani J, Dunand VA, Nagelkerke NJD, Ball TB, Oyugi J, Njagi E, Gaur L, Brunham RB, Wade J, Rowland-Jones S, Ngugi E, Bwayo J, Plummer FA. Influence of HLA supertypes on susceptibility and resistance to human immunodeficiency virus type 1 infection. J Infect Dis 2000; 181: 1581-9. | PubMed |

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  31. 1999

  32. Pinto LA, Berzofsky JA, FOWKE KR, Little RA, Merced-Galindez F, Humphrey R, Ahlers J, Dunlop N, Nara P, Shearer GM, Yarchoan R. HIV-specific immunity following immunization with HIV synthetic envelope peptides in asymptomatic HIV-infected patients. AIDS 1999, 13:2003-2012. | PubMed |
  33. Plummer FA, Ball TB, Kimani J and FOWKE KR. Resistance to HIV-1 infection among highly exposed sex workers in Nairobi: What mediates protection and why does it develop? Immunology Letters 1999, 66:27-34 | PubMed |

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  34. 1998

  35. Chougnet C, FOWKE KR, Mueller BU, Smith S, Zuckerman J, Jankelevitch S, Steinberg S, Luban N, Pizzo PA, Shearer GM. Protease inhibitor and triple-drug therapy: cellular immune parameters are not restored in pediatric AIDS patients after 6 months of treatment. AIDS 1998, 12:1-10. | PubMed |
  36. Rowland-Jones SL, Dong T, FOWKE KR, Kimani J, Krausa P, Newell H, Blanchard T, Ariyoshi K, Oyugi J, Ngugi E, Bwayo J, MacDonald KS, McMichael AJ, and Plummer FA. Cytotoxic T-cell responses to multiple conserved HIV epitopes in HIV-resistant prostitutes in Nairobi. Journal of Clinical Investigation 1998, 102:1758-65. | PubMed |
  37. FOWKE KR, Dong T, Rowland-Jones SL, Oyugi J, Rutherford WJ, Kimani J, Krausa P, Bwayo J, Simonsen JN, Shearer GM, Plummer FA. HIV-1 resistance in Kenyan sex workers is not associated with altered cellular susceptibility to HIV-1 infection or enhanced chemokine production. AIDS Research and Human Retroviruses 1998, 14:1521-1530. | PubMed |
  38. Simonsen JN, FOWKE KR, MacDonald KS and Plummer FA. HIV Pathogenesis: Epidemiology and mechanisms of susceptibility and disease progression. Current Opinion in Microbiology 1998, 1:423-429. | PubMed |

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  39. 1997

  40. FOWKE KR, D’Amico R, Chernoff DN, Pottage J, Bensen C, Sha B, Kessler HA, Landay AL, Shearer GM. Immunologic and virologic evaluation after influenza vaccination of HIV-1 infected patients. AIDS 1997; 11:1013-1021 | PubMed |

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  41. 1996

  42. FOWKE KR, Nagelkerke NJD, Kimani J, Simonsen JN, Anzala AO, Bwayo J, MacDonald KS, Ngugi EN, Plummer FA. Resistance to HIV-1 infection among prostitutes. Lancet 1996; 348:1347-51. | PubMed |

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  43. 1995

  44. Nath A, Hartloper V, Furer M, FOWKE KR. Infection of human fetal astrocytes with HIV-1: Viral tropism and the role of cell to cell contract in viral transmission. J Neuropath Exp Neurol 1995; 54:320-330. | PubMed |
  45. FOWKE KR, Plummer FA, Simonsen JN. Genetic analysis of human genomic DNA recovered from minute amounts of serum or plasma. J Immunol Meth 1995;180:45-51. | PubMed |

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  46. 1992

  47. Dawood MR, Allan R, FOWKE KR, Embree J, Hammond GW. Development of oligonucleotide primers and probes against structural and regulatory genes of human immunodeficiency virus type 1 (HIV-1) and their use for amplification of HIV-1 provirus by using polymerase chain reaction. J Clin Microbiol 1992;30:2279-2283. | PubMed |

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