Lesley E. Smythies, Ph.D.

Associate Professor of Medicine

Phone: 205-975-9254

Dr. Smythies earned both her B.S. in biology and her Ph.D. in physiology at Kings College, London University, England. She then did postdoctoral fellowships in the Department of Physiology and Biophysics at UAB and the Department of Biology at the University of York, England. She returned to UAB and joined the Department of Medicine as a Research Associate in 1998, advancing to Research Assistant Professor in 2002.

Dr. Smythies’ research focus is the mucosal immune response to parasite and bacterial pathogens. She focused originally on pulmonary immunology, helping to define the T cell cytokine regulation of the host response to Schistosoma mansoni. She went on to elucidate the role of interferon-g regulation of nitric oxide production in host defense against African trypanosome infections. Recently, she turned her investigative attention to the mucosal immune response to Helicobacter pylori. Using a mouse model of the infection that she developed, she has shown that H. pylori inflammation is Th1-mediated and with colleagues is developing a vaccine for the infection. Another focus of her work is the mechanism of the global, down-regulated inflammatory response of intestinal macrophages. In highly novel studies, she has discovered that the lamina propria stroma plays a critical role in monocyte differentiation into non-inflammatory intestinal macrophages and is elucidating the defective signal transduction pathway(s) underlying the down-regulated inflammatory response of intestinal macrophages. Finally, her laboratory is investigating the immunobiology of intestinal dendritic cells in healthy mucosa and inflamed mucosa from patients with Crohn's disease.

Selected Publications

Smythies, L.E., Pemberton, R.M., Coulson, P.S., and Wilson, R.A. T cell-derived cytokines associated with pulmonary immune mechanisms in mice vaccinated with irradiated cercarie of Schistosoma mansoni. J. Immunol. 148:1512-1518, 1992.
Smythies, L.E., Coulson, P.S., and Wilson, R.A. Monoclonal antibody to IFN-gamma abrogates immunity to Schistosoma mansoni in mice vaccinated with attenuated cercariae. J. Immunol. 149: 3654-3658, 1992.
Mountford, A.P., Coulson, P.S., Pemberton, R.M., Smythies, L.E., and Wilson, R.A. The generation of IFN-gamma producing lymphocytes in skin-draining lymph nodes, and their recruitment to the lungs, is associated with protective immunity to Schistosoma mansoni. Immunology 75:250-256, 1992.
Wilson, R.A., Coulson, P.S., Betts, C., Dowling, M-A., and Smythies, L.E. Impaired immunity and altered pulmonary responses in mice with a disrupted interferon-gamma receptor gene exposed to the irradiated Schistosoma mansoni vaccine. Immunology. 87: 275-282, 1996.
Mabbott, N.A., Coulson, P.S., Smythies, L.E., Wilson, R.A., and Sternberg, J.M. African trypanosome infections that lack the interferon-gamma receptor gene: nitric oxide-dependent and –independent suppression of Tcell prolifative responses and the development of anaemia. Immunology. 94:476-480, 1998.
Novak, M. J., Smythies, L.E., McPherson, S.A., Smith, P.D., and Morrow, C.D. Poliovirus replicons encoding the B subunit of Helicobacter pylori urease elicit a Th1 immune response. Vaccine. 17: 2384-2391, 1999.
Smythies, L.E., Waites, K.B., Lindsey, J.R., Harris, P.R., Ghiara, P., and Smith, P.D. Helicobacter pylori–induced mucosal inflammation is Th1-mediated and exacerbated in interleukin-4, but not interferon-gamma, gene-deficient mice. J. Immunol. 165:1022-1029, 2000.
Smythies, L.E., Chen, J-A., Lindsey, J.R., Ghiara, P., Smith, P.D., and Waites, K.B. Quantitative analysis of Helicobacter pylori infection in a mouse model. J. Immunol. Meth. 242:67-78, 2000.
Smith, P.D., Smythies, L.E., Mostellar-Barnum, M., Sibley, D., Russell, M., Merger, M., Sellers, M. T., Orenstein, J. M., Shimada, T., Graham, M.F. and Kubagawa, H. Intestinal macrophages lack CD14 and CD89 and consequently are downregulated for LPS- and IgA-mediated activities. J. Immunol. 167: 2651-2656, 2001.
Smythies, L.E., Sellers, M., Clements, R.H., Mosteller-Barnum, M., Meng, G., Benjamin, W.H., Orenstein, J.M. and Smith, P.D. Human intestinal macrophages display profound inflammatory anergy despite avid phagocytic and bacteriocidal activity. J. Clin. Invest. 115:66-75, 2005.

lesmy@uab.edu

Selected Publications

Smythies, L.E., Pemberton, R.M., Coulson, P.S., and Wilson, R.A. T cell-derived cytokines associated with pulmonary immune mechanisms in mice vaccinated with irradiated cercarie of Schistosoma mansoni. J. Immunol. 148:1512-1518, 1992.

Smythies, L.E., Coulson, P.S., and Wilson, R.A. Monoclonal antibody to IFN-gamma abrogates immunity to Schistosoma mansoni in mice vaccinated with attenuated cercariae. J. Immunol. 149: 3654-3658, 1992.

Mountford, A.P., Coulson, P.S., Pemberton, R.M., Smythies, L.E., and Wilson, R.A. The generation of IFN-gamma producing lymphocytes in skin-draining lymph nodes, and their recruitment to the lungs, is associated with protective immunity to Schistosoma mansoni. Immunology 75:250-256, 1992.

Wilson, R.A., Coulson, P.S., Betts, C., Dowling, M-A., and Smythies, L.E. Impaired immunity and altered pulmonary responses in mice with a disrupted interferon-gamma receptor gene exposed to the irradiated Schistosoma mansoni vaccine. Immunology. 87: 275-282, 1996.

Novak, M. J., Smythies, L.E., McPherson, S.A., Smith, P.D., and Morrow, C.D. Poliovirus replicons encoding the B subunit of Helicobacter pylori urease elicit a Th1 immune response. Vaccine. 17: 2384-2391, 1999.

Smythies, L.E., Waites, K.B., Lindsey, J.R., Harris, P.R., Ghiara, P., and Smith, P.D. Helicobacter pylori–induced mucosal inflammation is Th1-mediated and exacerbated in interleukin-4, but not interferon-gamma, gene-deficient mice. J. Immunol. 165:1022-1029, 2000.

Smythies, L.E., Chen, J-A., Lindsey, J.R., Ghiara, P., Smith, P.D., and Waites, K.B. Quantitative analysis of Helicobacter pylori infection in a mouse model. J. Immunol. Meth. 242:67-78, 2000.

Smythies, L.E., Sellers, M., Clements, R.H., Mosteller-Barnum, M., Meng, G., Benjamin, W.H., Orenstein, J.M. and Smith, P.D. Human intestinal macrophages display profound inflammatory anergy despite avid phagocytic and bacteriocidal activity. J. Clin. Invest. 115:66-75, 2005.