Select Faculty Member Mark R. Brown Donald E. Champagne Daniel G. Colley Harry W. Dickerson, Jr. Roberto Docampo Stephen L. Hajduk Jessica Kissinger Patrick J. Lammie Kojo A. Mensa-Wilmot Julie M. Moore Silvia N.J. Moreno Ynes R. Ortega David S. Peterson Pejman Rohani Robert Sabatini Mike R. Strand Boris Striepen Rick L. Tarleton

Daniel G. Colley, Ph.D.
Director, Center for Tropical and Emerging Global Diseases
Professor of Microbiology
Professor of Cellular Biology (courtesy appointment)

Office: Room 330B, Coverdell Center

Office telephone: 706-542-4112
E-mail: dcolley@uga.edu
Laboratory telephone: 706-542-4689
FAX: 706-542-3582

Washing cars and trucks in Lake Victoria - Kisumu, Kenya

Research
Our laboratory uses field, whole animal, cellular and molecular approaches to further an understanding of the immunobiology of schistosomiasis in people. We focus on immunopathology, immunoregulation and resistance to reinfection. Schistosomiasis is a parasitic worm infection that people acquire by going into fresh water that contains schistosome-infected snails, the intermediate host. Globally, about 200 million people are infected with this intravascular worm. Twenty million of those infected suffer severe, life-threatening disease, while another 100 million experience more subtle morbidity due to their schistosomiasis, making it a major public health threat in endemic areas of the world. Schistosomes live for years inside the blood vessels of those infected. There the female worms produce large numbers of eggs, which the males fertilize. Some of the eggs are excreted out of the body and get into fresh water, to complete the life cycle. However some of the eggs are swept by the blood flow to the liver and other organs, where they induce morbidity - which may primarily be due to host immune responses against the eggs. Our research seeks to understand the roles of the immune system in the pathogenesis, regulation, and resistance observed during this chronic disease, and investigates how to translate our findings to contribute to the control of its transmission and the widespread morbidity it causes. In addition, because of the chronic nature of schistosomiasis, a better understanding of the immune interactions in this setting may shed light on other chronic antigenic exposures, such as organ transplantation, autoimmune diseases and cancer. Our human studies of Schistosoma mansoni infections have been done through extensive collaborations in the West Indies, Brazil, and Egypt. Currently, essentially all of our research is done in collaboration with Dr. Diana Karanja's laboratory at the Kenya Medical Research Institute (KEMRI) in Kisumu, Kenya.

Asembo Bay, Kenya: a fishing village on Lake Victoria where exposure to potential schistosome transmission occurs through daily living.

Our major research emphasis in all of these settings is to understand how the host and the parasite interact and counter-balance each other to establish stable, chronic, fairly well tolerated infections. This relatively balanced situation is what occurs in most people harboring these organisms. Unfortunately, in a proportion of those infected, adverse outcomes occur, and result in severe morbidity and mortality, while even a larger proportion suffer more subtle levels of morbidity, such as anemia, hematuria, and polyposis, as well as phyiscal and cognitive developmental deficits. We want to determine the mechanisms responsible for these different outcomes. Our laboratory has described, and is defining the roles of T regulatory lymphocytes in the regulation of both pathogenesis and resistance to reinfection. More specifically In regard to anti-schistosome resistance mechanisms, we have, in Kenya, described the development of immune resistance in some people who are occupationally repeatedly exposed to schistosome infection and treated for their schistosomiasis. These observations are now being followed by establishing which immune response mechanisms correlate with resistance vs. continued susceptibility. Such longitudinal studies are challenging, in terms of both the science involved and the logistics required, but they are beginning to yield some insights into the immune cells, antibodies and even genotypes that contribute to a partially resistance state. At some point these findings should contribute to the quest for a vaccine against schistosomiasis.

Cross-section of a male & female S. mansoni adult worm pair in copula in a mouse venule.

Representative Publications from the Last 10 Years:

Montesano, M.A., Colley, D.G., Eloi-Santos, S., Freeman, G.L., Jr. and Secor, W.E. (1999) Neonatal idiotypic exposure slaters subsequent cytokine, pathology and survival patterns in experimental Schistosoma mansoni infections. J. Exp. Med. 189:637-645.

Montesano, M.A., Colley, D.G., Freeman, G.L., Jr. and Secor, W.E. (1999) Neonatal exposure to idiotype induces Schistosoma mansoni egg antigen specific cellular and humoral immune responses. J. Immunol. 163:898-905.

Karanja, D.M.S., Hightower, A.W., Colley, D.G., Mwinzi, P.N.M., Galil, K., Andove, J. and Secor, W.E. Longitudinal demonstration of the development of resistance to reinfection with Schistosoma mansoni in occupationally exposed adults and the effect of HIV-1 coinfection on susceptibility to schistosomiasis. The Lancet 360:592-596, 2002.

Handzel, T, Karanja, D.M.S, Addiss, D.G., Hightower, A.W., Rosen, D.H., Colley, D.G., Andove, J, Slutsker, L, and Secor, W.E. Geographic distribution of schistosomiasis and soil-transmitted helminths in western Kenya - implications for anti-helminthic mass treatment. Am. J. Trop. Med. Hyg., 69:318-323, 2003.

Mwinzi, P.N.M., Karanja, D.M.S., Kareko, I., Magak, P.W., Orago, A.S.S., Colley, D.G., and Secor, W.E. Evaluation of hepatic fibrosis in persons co-infected with Schistosoma mansoni and human immunodeficiency virus-1. Am. J. Trop. Med. Hyg., 71:783-786, 2004.

Colley, D.G., Sasser, L.E. and Reed, A.M. PD-L2+ dendritic cells and PD-1+ CD4+ T cells in schistosomiasis correlate with morbidity. Parasite Immunol., 27:45-53, 2005.

Beard, C.B., Fox, M.R., Lawrence.G.G., Guarner, J., Hanzlick, R.L., Huang, L., del Rio, C., Rimland, D., Duchin, J.S., and Colley, D.G. Genetic differences in Pneumocystis isolates from immunocompetent infants and from adults with AIDS: Epidemiological implications. J. Infect. Dis.,192:1815-1818, 2005.

Ganley-Leal, L.M., Mwinzi, P.N., Cetre-Sossah, C.B., Andove, J., Hightower, A.W., Karanja, D.M.S., Colley, D.G., and Secor, W.E. The role of eosinophils in protection against infection with Schistosoma mansoni and the effect of HIV-1 co-infection in humans. Infect. Immunity, 74:2169-2176, 2006.

Ganley-Leal, L.M., Mwinzi, P.N.M., Cetre-Sossah, C.B., Andove, J., Hightower, A.W., Karanja, D.M.S., Colley, D.G. and Secor, W.E. Higher percentages of circulating mast cell precursors correlate with susceptibility to reinfection with Schistosoma mansoni. Am. J. Trop. Med. Hyg., 75:1053-1057, 2006.

Cetre-Sossah, C.B., Montesano, M.A., Freeman, G.L., Jr., Willard, M.T., Colley, D.G., and Secor, W.E. Early responses associated with chronic pathology in murine schistosomiasis. Parasite Immunol., 29:241-249, 2007.

Watanabe, K., Mwinzi, P.N.M., Black, C.L., Muok, M.M.O., Karanja, D.M.S., Secor, W.E., Colley, D.G.  T regulatory cell levels decrease in people infected with Schistosoma mansoni upon effective treatment.  Am. J. Trop. Med. Hyg., 77:676-682, 2007.

Colley, D.G. and Secor, W.E. A Schistosomiasis Research Agenda.  PLoS NTD, 1(2):e32, 2007.

Harvesting sand off the bottom of Lake Victoria - Usoma, Kenya

Mt. Kilimanjaro (Tanzania); Elephants (Kenya)