The major focus of current research in my laboratory is to understand the cellular and molecular mechanisms involved in the innate immune response to inhaled particulate pollutants including diesel exhaust particles, atmospheric allergens. In particular, my laboratory studies the mechanisms responsible for the altered functional behavior of dendritic cells (DC) on activation by atmospheric pollutants such as ambient environmental particulate matter and diesel exhaust particulates. These particulate pollutants have been shown by us to dramatically alter the state of differentiation and maturation of both human and murine myeloid DC.

       We have recently reported the functional consequences and mechanisms involved during the interaction of particulate matter and human DC and identified dramatic effects of particulate pollution on the Toll-Like and Nod-Like family of microbial pattern-recognition receptors such as TLR2, TLR4 and NOD-1/2. We have identified the importance of the p38 MAP kinase and ERK1/2 pathways of signal transduction and suspect the involvement of PI3 kinase and JNK1/2 pathways of cellular activation as well in the transcriptional mobilization of NF-kappa B and AP-1.

      Two lines of investigation form the theme of my research program in this context:

• To identify mechanisms responsible for Th2-type immune responses in asthma and allergic sensitization
• To understand the role played by lung DC and pattern-recognition receptor signaling in the microbiological-mediated exacerbations of asthma on exposure to environmental pollutants.

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Recent Publications

Porter M, Karp M, Killedar S, Bauer SM, Guo J, Williams D, Breysse P, Georas SN, Williams MA. Diesel-Enriched Particulate Matter Functionally Activates Human Dendritic Cells. 2007 . Am J Respir Cell Mol Biol. 2007 Jul 13; [Epub ahead of print]

Cheadle C, Watkins T, Fan J, Williams MA, Georas SN, Hall J, Rosen A, Barnes KC."> GSMA: Gene set matrix analysis, an automated method for rapid hypothesis testing of gene expression data. Bioinformatics and Biology Insights 1:49-62, 2007.

Williams MA, Cheadle C, Watkins T, Tailor A, Killedar SY, Breysse P, Barnes K, Georas SN."> TLR2 and TLR4 as Potential Biomarkers of Environmental Particulate Matter Exposed Human Myeloid Dendritic Cells. Biomarker Insights 2: 225-239, 2007.

Williams MA, Porter M, Horton M, Guo J, Roman J, Williams D, Breysse P, Georas SN. Ambient particulate matter directs nonclassic dendritic cell activation and a mixed TH1/TH2-like cytokine response by naive CD4+ T cells. Journal of Allergy and Clinical Immunology 119:488-497, 2007.

Georas SN, Berdyshev E, Hubbard W, Gorshkova I, Usatyuk P, Saatian B, Myers A, Williams MA, Xiao H, Liu M, Natarajan V. Lysophosphatidic acid is increased in bronchoalveolar lavage fluids during allergic inflammation. Clinical and Experimental Allergy 37:311-322, 2006.

Chen R, Roman, J, Guo J, West E, McDyer J, Williams MA, Georas SN. Lysophosphatidic acid modulates the activation of human monocytes-derived dendritic cells. Stem Cells and Development 15: 797-804, 2006.

Parker GC, Anastassova-Kristeva M, Dajani N, Eisenberg L, Rao MS, Williams MA, Sanberg PR, English D. Stem Cells: From Shibboleths Toward Functional Definition. Stem Cells and Development 14:463-468, 2005.

Williams MA, Turchan J, Lu Y, Nath A, Drachman DB. Protection of human cerebral neurons from neurodegenerative insults by gene delivery of soluble tumor necrosis factor p75 receptor. Experimental Brain Research, E-pub Ahead of Print, April 13th, 2005.

Drachman DB, Wu J-M, Miagkov A, Williams MA, Adams RN, Wu B. Specific immunotherapy of experimental myasthenia by genetically engineered APCs: The "guided missile" strategy. Annals of the New York Academy of Sciences 998, 520-532, 2003.

Williams MA*, Rhoades CJ, Provan D, Newland AC. In vitro cytotoxic effects of stabilizing sugars within human intravenous immunoglobulin preparations against the human macrophage THP-1 cell-line. Hematology 8: 285-294, 2003.

English D, Williams MA*. The therapeutic promise of non-embryonic stem cells, whereÕs the beef? Journal of Hematotherapy and Stem Cell Research 12(5): 465-466, 2003.

Williams MA*, Trout R, Spector SA. HIV-1 gp120 modulates the immunological function and expression of accessory and co-stimulatory molecules of monocyte-derived dendritic cells. Journal of Hematotherapy and Stem Cell Research 11:829-847, 2002.