Return to the faculty index...
The focus of my research is defining the intricate chemokine pathways involved
in the recruitment of leukocytes into areas of microbial infections. While the
information on individual chemokines and chemoattractants is growing, little
attention has been placed on the interplay of multiple chemokines. A myriad
of cytokines and chemokines are produced by macrophages as part of the first
line of immune defense to combat pathogens and to recruit new leukocytes into
areas under siege. For certain virulent pathogens or in immunocompromised individuals,
these defenses can be altered to turn the macrophage’s cellular machinery
into factories of pathogen production. Understanding these mechanisms of invasion/evasion
is critical in developing treatment to eliminate pathogens without exacerbating
the infection. A key question in this area remains: while many chemokines are
produced by macrophages in response to infection, which ones are specifically
responsible for the recruitment of other immune cells for a particular infection?
My planned research directives are centered on elucidating this answer including
taking approaches to understanding these events such as the kinetics of infection,
receptor utilization, signaling events, chemokine and cytokine production by
the infected host cells, and response events by the uninfected cells.
Hale-Donze, H., Greenwell-Wild, T., Mizel, D., Doherty, T.M., Chatterjee, D., Orenstein, J.M., and Wahl, S.M. (2002) Mycobacterium avium complex (MAC) promotes recruitment of monocyte hosts for HIV-1 and bacteria. Journal of Immunology, 169:3854-62
Wahl, S. M., Greenwell-Wild, T., Peng, G., Hale-Donze, H., Doherty, T. M., Mizel, D., and J. M. Orenstein. (1998) Mycobacterium avium complex (MAC) augments macrophage HIV-1 production and increases CCR5 expression. Proceedings of the National Academy of Science, U.S.A. 95:12574-9
Ashcroft, G.S., Lei, K., Jin, W., Longenecker, G., Kulkarni, A.B., Greenwell-Wild, T., Hale-Donze, H., McGrady, G., Song, X-Y., and S.M. Wahl. (2000) Secretory leukocyte protease inhibitor (SLPI) mediates non-redundant functions necessary for normal wound healing. Nature Medicine. 6:1147-1153
Wahl, S.M., Greenwell-Wild, T., Hale-Donze, H., Moutsopoulos, N., and J.M Orenstein. (2000) Permissive factors for HIV-1 infection of macrophages. Journal of Leukocyte Biology. 68:303-310. (Cover)
Hale Donze, H., Cummins, Jr., J. E. , Schwiebert, R. S., Kantele, A., Han, Y., Fultz, P. N., Jackson, S., and J. Mestecky. (1997) HIV-1/simian virus infection of human and nonhuman primate lymphocytes result in the migration of CD2+ T cells into the intestine of engrafted SCID mice. Journal of Immunology. 160:2506-2513.
Hale Donze, H., Cummins Jr., J. E., Schwiebert, R. S., Fultz, P. N., Jackson, S., and J. Mestecky. (1998) Human and nonhuman primate lymphocytes engrafted into SCID mice reside in unique mesenteric lymphoid structures. Journal of Immunology. 161: 1306-1312