Ph.D., McGill University

Tel: 617-552-1186
E-mail: williauy@bc.edu

Fields of Interest: Central nervous system macrophages, neuroAIDS, AIDS pathogenesis, monocyte/macrophage biology

Academic Profile

My laboratories major research activity centers on CNS inflammation and normal and diseased states.  Specifically, we focus on the role of CNS macrophages and CD8 T lymphocytes in pathogenesis of lentiviral infection.  This work includes: a) studies to define subpopulations of macrophages in the CNS and their precursors in blood and bone marrow, b) the role of the cellular immune system especially CD8 T cells controlling monocyte/macrophage activation and CNS pathogenesis, and c) developing drugs that target HIV and SIV infected/activated macrophages resulting in cell death or deactivation.  In addition, we are exploring an exciting field of emergent populations of monocytes and dendritic cells that are expanded with disease.  This works uses a monkey model of rapid, consistent AIDS and neuroAIDS, CD8 T lymphocyte depletion, MR spectroscopy, monocyte/macrophage biology and immunology.

View Ken Williams’ research image gallery here>

Representative Publications

Lentz, M., Kim, W.K., Lee, V., Bazner, S., Halpern, E.F., Venna, N., Williams, K., Rosenberg, E.S., Gonzalez, R.G.  2009. Changes in MRS neuronal markers and T cell phenotypes observed during early HIV infection.  Neurology 72: 1465–1472.

Hasegawa, A., Liu, H., Ling, B., Borda, J., Alvarez, X., Sugimoto, C., Vinet-Oliphant, H., Kim, W.K., Williams, K., Reibero, R.M., Lackner, A.A., Veazey, R.D., Kuroda, M.J.  2009. The level of monocyte turnover predicts disease progression in the macaque model of AIDS.  Blood: 2009, Apr. 21 (Epub ahead of print).

Williams, K.C., and Burdo, T.H. 2009. HIV and SIV infection: the role of cellular restriction and immune responses in viral replication and pathogenesis. APMIS 117(5-6): 400–412.

Soulas, C., Donahue, R.E., Dunbar, C.E., Persons, D.A.,  Alvarez, X., and Williams, K.C. 2009. Genetically modified CD34+ hematopoietic stem cells contribute to turnover of brain perivascular macrophages in long-term repopulated primates. American Journal of Pathology 174: 1808–1817.

Veazey, R., Acierno, P.M., Baumeister, S., Foster, G.J., Rett, M., Newberg, M.H., Kuroda, M.J., Williams, K., Keim, E.Y., Wolinsky, S.M., Reiber, E.P., Piatak, M., Lifson, J.D., Montefiori, D.C., Hirsch, V., Schmitz, J.E. 2008. Increased loss of CCR5+CD45RA-CD4+ T cells in CD8 lymphocyte depleted simian immunodeficiency virus infected monkeys. Journal of Virology 82: 5618–30.

Ratto-Kim, S., Chuenhitra, T., Pulliam, L., Paris, R., Sukwit, S., Sithinamsuwan, P., Nihinandana, S., Sataport, T., Shiramizu, B., de Souza, M., Williams, K., Kim, J.H., Shikuma, C., Valcour, V.G.  2008. Increased expression of monocyte markers in HIV-1 infected individuals with or without HIV associated dementia and normal controls in Bangkok Thailand. Journal of Neuroimmunology 195: 100–107.

Wutrich, C., Kesari, S., Kim, W.-K., Williams, K., Gelman, R., Elmeric, D., De Girolami, U., Joseph, J.T., Hedley-White, T., Koralnik, I.L. 2006. Characterization of lymphocytic infiltrates in progressive multifocal leukoencephalopathy: Co-localization of CD8+ T cells with JCV-infected glial cells. Journal of NeuroVirology 12: 116–128.

Williams, K., Westmoreland, S., Greco, J., Ratai, E., Lentz, M., Kim, W.-K., Fuller, R., Kim, J.P., Autissier, P., Sehgal, P.K., Schinazi, R., Bischofberger, N., Piatak, M., Lifson, J., Masliah, E., González, R.G. 2005. Magnetic resonance spectroscopy reveals a role of activated blood monocytes contributing to neuronal injury in simian immunodeficiency neuroAIDS. The Journal of Clinical Investigation 115: 2534–2545.

Kim, W.K., Alvarez, X., Fisher, J., Bronfin, B., Westmoreland, S., McLaurin, J., Williams, K. 2005. CD163 identifies perivascular macrophages in normal and viral encephalitic brains and potential precursors to perivascular macrophages in blood. American Journal of Pathology 168: 822–834.

Kim, W.K., Corey, S., Chesney, G., Knight, H., Klumpp, S., Wuthrich, C., Letvin, N., Koralnik, I.J., Veazey, R., Lackner, A., Williams, K. 2004. Identification of T lymphocytes in simian immunodeficiency virus encephalitis: Distribution of CD8 T cells in association with central nervous system vessels and virus. Journal of NeuroVirology 10: 315–325.

Hickey, W.F., Williams, K., Corey, S., Kim, W.K. 2004. Mononuclear phagocyte heterogenieity and the blood brain barrier: a model for HIV-1 neuropathogenesis.  In: The neurology of AIDS. Gendelman, H.E., Lipton, S.A., Swindells, S. (eds). Oxford University Press.

Williams, K., and Hickey, W.F. 2002. Central nervous system damage, monocytes and macrophages, and neurological disorders in AIDS.  Annual Review of Neuroscience 25: 537–62.

Williams, K., Schwartz, A., Corey, S., Orandle, M., Kennedy, W., Thompson, B., Alvarez, X., Brown, C., Gartner, S., and Lackner, A. 2002. Proliferating cellular nuclear antigen (PCNA) expression as a marker of perivascular macrophages in SIV encephalitis. American Journal of Pathology 161: 575–585.

Williams, K., Corey, S., Westmoreland, S., Pauley, D., Knight, H., deBakker, C., Alvarez, X., Lackner, A.A. 2001. Perivascular macrophages are the primary cell type productively infected by SIV in the brain of macaques:  Implications for the neuropathogenesis of AIDS. The Journal of Experimental Medicine 193: 905–915.

Swingler, S., Mann, A., Jacque, J.M., Brichacek, B., Sasseville, V.G., Williams, K., Lackner, A.A., Gendelman, H.E., Janoff, E., Wang, R., Fisher, D., Stevenson, M. 1999. HIV-1 Nef mediates lymphocyte chemotaxis and activation by infected macrophages. Nature Medicine 5: 997–1003.

Klein, R.S., Williams, K., Alvarez-Hernandez, X., Westmoreland, S., Lackner, A.A., Luster, A.D. 1999. Chemokine receptor expression and signaling in macaque and human fetal neurons and astrocytes: implications for the neuropathogenesis of AIDS, Journal of Immunology 163: 1636–1646.

 

 

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