Kenneth C. Williams
professor of biology
professor of biology
Ph.D., McGill University
Phone: 617-552-1186
E-mail: kenneth.williams.3@bc.edu
Fields of Interest
Central nervous system macrophages, neuroAIDS, AIDS pathogenesis, monocyte/macrophage biology.
Academic Profile
My laboratory's 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 work uses a monkey model of rapid, consistent AIDS and neuroAIDS, CD8 T lymphocyte depletion, MR spectroscopy, monocyte/macrophage biology and immunology.
Representative Publications
Williams K, Hickey WF, Burdo TH and Soulas C. Mononuclear phagocytes. In: The Neurology of AIDS. HE Gendelman, I Grant, IP Everall, HS Fox, HA Gelbard, SA Lipton, S Swindells (eds). 2012 Chapman and Hall, New York, NY.
Williams K and Burdo TH. Monocyte Mobilization, Activation Markers, and Unique Macrophage Populations in the Brain: Observations From SIV infected Monkeys Are Informative With Regard to Pathogenic Mechanisms of HIV Infection in Humans. Journal of Neuroimmune Pharmacology, accepted November 25, 2011.
Burdo TH, Orzechowski K, Knight HL, Miller AD, Williams KC. Dorsal root ganglia damage in SIV-infected rhesus macaques: An animal model of HIV-induced sensory neuropathy. American Journal of Pathology, accepted December 2, 2011.
Zanni MV*, Burdo TH*, Makimura H, Williams KC, Grinspoon S. Relationship between Monocyte/Macrophage Activation Marker Soluble CD163 and Insulin Resistance in Obese and Normal-Weight Subjects. Clinical Endocrinology, accepted October 31, 2011. *Authors contributed equally.
Burdo TH, Lo J, Abbara S, Wei J, Delelys ME, Preffer F, Rosenberg ES, Williams KC, Grinspoon S. Soluble CD163, a Novel Marker of Activated Macrophages, Is Elevated and Associated With Noncalcified Coronary Plaque in HIV-Infected Patients. J Infect Dis. 2011 Oct;204(8):1227-36.
Strickland S, Gray R, Lamers SL, Burdo TH, Huenink E, Nolan DJ, Nowlin B, Alvarez A, Midkiff CC, Goodenow MM, Williams K, Salemi M. Significant Genetic Heterogeneity of the SIVmac251 Viral Swarm Derived From Different Sources. AIDS Research and Human Retoviruses, Apr 27. [Epub ahead of print].
Burdo TH, Lentz MR, Autissier P, Krishnan A, Halpern E, Letendre S, Rosenberg ES, Ellis RJ and Williams KC. Soluble CD163 made by monocyte/macrophages is a novel marker of HIV activity in early and chronic infection prior to and after anti-retroviral therapy. Journal of Infectious Diseases, Jul;204(1):154-63.
Soulas C, Conerly-Midiff C, Kim W-K, Burdo TH, Alaverz A, Lackner A, Williams KC Recently infiltrating MAC387+ monocyte/macrophages: a third macrophage population involved in SIV and HIV encephalitic lesion formation, American Journal of Pathology, 2011 May;178(5):2121-35. PMID: 21514427.
Campbell JH, Burdo TH, Autissier P, Bombardier JP, Westmoreland SV, Soulas C, González RG, Ratai E-M, Williams KC, Minocycline Inhibition of Monocyte Activation Correlates with Neuronal Protection in SIV NeuroAIDS, PLoS One. 2011 April 6.
Ratai E-M, Pilkenton S, He J, Fell R, Bombardier JP, Joo C-G, Lentz MR, Kim W-K, Burdo TH, Autissier P, Annamalai L, Curran E, O’Neil S, Westmoreland SV, Williams KC, Masliah E, González RG CD8+ Lymphocyte Depletion without SIV Infection does not Produce Metabolic Changes or Pathological Abnormalities in the Rhesus Macaque Brain, J Med Primatol. 2011 Apr 4. doi: 10.1111/j.1600-0684.2011.00475.x. [Epub ahead of print].
Ratai E-M, Annamalai L, Burdo TH, Joo CG, Bombardier JP, Fell R, Hakimelahi R, He J, Lentz MR, Campbell J, Curran E, Halpern EF, Masliah E, Westmoreland SV, Williams KC, González RG, Brain creatine elevation and N-acetylaspartate reduction indicates neuronal dysfunction in the setting of enhanced glial energy metabolism in a macaque model of NeuroAIDS. Magn Reson Med. 2011 Mar 4. doi: 10.1002/mrm.22821. [Epub ahead of print]
Autissier, P., Soulas, C., Burdo, T., Williams, K. 2010. Immunophenotyping of lymphocyte, monocyte and dendritic cell subsets in normal rhesus macaques by 12-color flow cytometry: clarification and DC heterogeneity. Journal of Immunological Methods (in press).
Raitai, E., Bombardier, J., Joo, C.-G., Annamalai, L., Burdo, T., Campbell, J., Fell, R., Hakimelahi, R., He, J., Autissier, P., Lentz, M., Halpern, E., Masliah, E., Williams, K., Westmoreland, S., Gonzalez, R.G. 2010. Proton magnetic resonance spectroscopy reveals neuroprotection by oral minocycline in a nonhuman primate model of accelerated neuroAIDS. PloS ONE 5(5): e10523, doi:10.1371/journal.pone.0010523.
Burdo, T., Soulas, C., Orzechowski, K., Button, J., Krishnan, A., Sugimoto, C., Alvarez, X., Kuroda, M., and Williams, K. 2010. Increased monocyte turnover from bone marrow predicts severity of SIV encephalitis and correlates with CD163 levels in plasma. PloS Pathogens 6(4): e1000842.
Autisseri, P., Soulas, C., Burdo, T.H., and Williams, K. 2010. Evaluation of a 12-color flow cytometry panel to study lymphocyte, monocyte, and dendritic cell subsets in humans. Cytometry A: Jan. 22, 2010 [Epub ahead of print].
Kim, W.-K., Sun, Y., Do, H., Autissier, P., Halpern, E.F., Piatak, M. Jr., Lifson, J.D., Burdo, T.H., McGrath, M.S., and Williams, K. 2009. Monocyte heterogeneity underlying phenotypic changes in monocytes according to SIV disease stage. Journal of Leukocyte Biology: Oct. 20, 2009 [Epub ahead of print], doi:10.1189/jlb.0209082.
Lentz, M., Kim, W.K., Lee, V., Bazner, S., Halpern, E.F., Venna, N., Williams, K., Rosenberg, E.S., and 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., and Kuroda, M.J. 2009. The level of monocyte turnover predicts disease progression in the macaque model of AIDS. Blood 114(14): 2917-25.
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., and 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., and 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., and 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, and 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., and 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., and 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., and 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., and 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., and 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.