Lafuse, William P.

William P. Lafuse, Ph.D.

Professor
Department of Molecular Virology, Immunology and Medical Genetics

Contact Information:

Laboratory:
2178 Graves Hall
333 W. 10th Avenue
Columbus, Oh. 43210
Ph. (614) 292-0652

Research Interests:
Innate Immunity, Interaction of Mycobacterium avium and Mycobacterium tuberculosis with macrophages, Role of Nramp1 (natural resistance associated macrophage protein) in iron transport and macrophage mycobactericidal activity, signal transduction in macrophages by cytokines and catecholamines.

Research Summary:
The interaction of Mycobateria (M. avium and M.tuberculosis) with mouse and human macrophages is being investigated in studies on the effect of mycobacterial infection on macrophage cell signaling, transcriptional activation, and mRNA stability. In mice, innate immunity to intracellular pathogens is controlled by Nramp1 (natural resistance associated macrophage protein.), which is expressed in late endosomes that fuse with mycobacteria containing phagosomes . Nramp1 functions as iron transporter, which transports iron from the cytoplasm into the phagosome, where it acts as a catalysis for generation of oxidants, such as the hydroxyl radical, that mediate mycobacterial killing. Studies in the laboratory investigate the regulation of the iron transport function of Nramp1 and the effect of oxidants generated by Nramp1 mediated iron transport on macrophage transcriptional activation and mRNA stability. A second area of research investigates the pathways by which M. avium and M. tuberculosis infection of macrophages inhibits IFN-g activation of macrophages. A third area of research studies the effect of catecholamines, epinephrine and norepinephrine, on macrophage activation for mycobacterial killing and the role of cell signaling pathways activated by alpha and beta adrenergic receptors.

Selected Publications:

Chen, L., Boomershine, C., Wang, T., Lafuse, W.P., and Zwilling, B.S. (1999) Synergistic interaction of catecholamine hormones and Mycbacterial avium results in the induction of interleukin-10 mRNA by peritoneal macrophages. J. Neuroimmunology 93:149-155.<

Zwilling, B.S, Kuhn, D.E., Wikoff, L., Brown, D., and Lafuse, W.P. (1999) The role of iron in Nramp1 mediated inhibition of growth. Infection and Immunity 67:1386-1392.

Hussain, S,, Zwilling, B.S., and Lafuse, W.P. (1999) Mycobacterium avium infection inhibits IFN-g JAK/STAT signaling and gene induction by down-regulation of the IFN-g receptor. J. Immunology 163:2041-9.

Kuhn, D.E., Baker, B.D., Lafuse, W.P., and Zwilling, B.S. (1999) Differential iron transport into phagosomes from RAW264.7 macrophage cell lines transfected with Nramp1Gly169 or Nramp1Asp169. J. Leukocyte Biol.66:113-9.

Boomershine, C.S., Lafuse, W.P., and Zwilling, B.S. (1999) b-2 adrenergic receptor stimulation inhibits nitric oxide generation by Mycobacterium avium infection. J. Neuroimmunology 101:68-75.

Lafuse, W.P, Alvarez, G.R., and Zwilling, B.S. (2000) Regulation of Nramp1 mRNA stability by oxidants and protein kinase C in RAW264.7 macrophages expressing Nramp1Gly169. Biochemical Journal (in press).