|Samuel J. Black
Professor of Veterinary and Animal Sciences, University of Massachusetts
Ph.D.: University of Edinburgh, Scotland
Molecular Basis of Innate Immunity Against Parasitic Protozoa
We are studying host control of African trypanosomes, tsetse fly-transmitted flagellate protozoa that live and replicate in the fluid compartment of host blood. The organisms cause fatal disease in people and domestic animals. Human trypanosomiasis is restricted to a few regions of Africa but likened to a sleeping dragon that can awake and spread like wildfire. Cattle trypanosomiasis is endemic in and excludes cattle from about 10 million square kilometers of Africa lying between 15° North and 20° South and comprising much of the humid and semi-humid zones. This region is haven to Cape buffalo which are resistant to trypanosomiasis.
Our investigations show that control of trypanosome infection in Cape buffalo correlates with broad-acting anti-trypanosome serum activity involving oxygen radicals generated during catabolism of purines by serum xanthine oxidase. Two features of the buffalo response are noteworthy. First, the presence of a high concentration of serum xanthine oxidase ensures the extracellular capability of producing significant quantities of reactive oxygen radicals. Secondly, an infection-associated decline in blood catalase activity occurs co-incident with clearance of the first parasitemic wave and augments the efficacy of the oxidative response by limiting the rate of catabolism of hydrogen peroxide which is the trypanocidal radical.
We want to characterize features of xanthine oxidase that affect its presence and concentration in serum, the sources and regulation of purine substrates in serum, and how infection causes the decline in serum and erythrocyte-associated catalase. These questions are of fundamental interest because whilst oxygen radicals can slay dragons they can also turn on their maker.
Wang L, Pawlak E, Johnson PJ, Belknap JK, Alfandari D, Black SJ. 2012. Effects of cleavage by a disintegrin and metalloproteinase with thrombospondin motifs-4 on gene expression and protein content of versican and aggrecan in the digital laminae of horses with starch gruel-induced laminitis.. American journal of veterinary research. 73(7):1047-56.
Pawlak E, Wang L, Johnson PJ, Nuovo G, Taye A, Belknap JK, Alfandari D, Black SJ. 2012. Distribution and processing of a disintegrin and metalloproteinase with thrombospondin motifs-4, aggrecan, versican, and hyaluronan in equine digital laminae.. American journal of veterinary research. 73(7):1035-46.
Goenka R, Guirnalda PD, Black SJ, Baldwin CL. 2012. B Lymphocytes provide an infection niche for intracellular bacterium Brucella abortus.. J Infect Dis. 206(1):91-8.
Bockstal V, Guirnalda P, Caljon G, Goenka R, Telfer JC, Frenkel D, Radwanska M, Magez S, Black SJ. 2011. T. brucei infection reduces B lymphopoiesis in bone marrow and truncates compensatory splenic lymphopoiesis through transitional B-cell apoptosis.. PLoS pathogens. 7(6):e1002089.
Black SJ, Guirnalda P, Frenkel D, Haynes C, Bockstal V. 2010. Induction and regulation of Trypanosoma brucei VSG-specific antibody responses.. Parasitology. 137(14):2041-9.
Loftus JP, Williams JM, Belknap JK, Black SJ. 2010. In vivo priming and ex vivo activation of equine neutrophils in black walnut extract-induced equine laminitis is not attenuated by systemic lidocaine administration.. Veterinary immunology and immunopathology. 138(1-2):60-9.
Loftus JP, Johnson PJ, Belknap JK, Pettigrew A, Black SJ. 2009. Leukocyte-derived and endogenous matrix metalloproteinases in the lamellae of horses with naturally acquired and experimentally induced laminitis.. Veterinary immunology and immunopathology. 129(3-4):221-30.
Black SJ. 2009. Extracellular matrix, leukocyte migration and laminitis.. Veterinary immunology and immunopathology. 129(3-4):161-3.
Coyne MJ, Cousin H, Loftus JP, Johnson PJ, Belknap JK, Gradil CM, Black SJ, Alfandari D. 2009. Cloning and expression of ADAM-related metalloproteases in equine laminitis.. Veterinary immunology and immunopathology. 129(3-4):231-41.
Loftus JP, Belknap JK, Stankiewicz KM, Black SJ. 2007. Laminar xanthine oxidase, superoxide dismutase and catalase activities in the prodromal stage of black-walnut induced equine laminitis.. Equine veterinary journal. 39(1):48-53.
Loftus JP, Black SJ, Pettigrew A, Abrahamsen EJ, Belknap JK. 2007. Early laminar events involving endothelial activation in horses with black walnut- induced laminitis.. American journal of veterinary research. 68(11):1205-11.
Guirnalda P, Murphy NB, Nolan D, Black SJ. 2007. Anti-Trypanosoma brucei activity in Cape buffalo serum during the cryptic phase of parasitemia is mediated by antibodies.. International journal for parasitology. 37(12):1391-9.
Black SJ, Lunn PD, Yin C, Hwang M, Lenz SD, Belknap JK. 2006. Leukocyte emigration in the early stages of laminitis.. Veterinary immunology and immunopathology. 109(1-2):161-6.
Black, S.J. , Lunn, DP., Hwang, M., Yin, C., Lenz, SD., Belknap, JK. 2006. Leukocyte emigration in the early stages of laminitis. Veterinary Immunology and Immunopathology. 109: 161-166.
Black, S.J., Seed, J.R. 2005. African Trypanosomiasis, In: Topley and Wilson 's Microbiology and Microbial Infections 10 th Edition, Ed, Frank Fox, Edward Arnold Ltd., Hodder Arnold Publishers ISBN 0 340 88568 8
Kitani H., Black S.J., Nakamura Y., Naessens J., Murphy N.B., Yokomizo Y., Gibson J., and F. Iraqi. (2002) Recombinant tumor necrosis factor alpha does not inhibit the growth of African trypanosomes in axenic cultures. Infect. Immun. 70:2210-4.
Wang, J., A.Van Praagh, E. Hamilton, Q. Wang, B. Zou, M. Muranjan, N.B. Murphy, S.J. Black. 2002, Serum xanthine oxidase: Origin, regulation and
Hatada, S., Seed, J.R., Barker, C., Hadjuk, S.L., Black, S.J. and Maeda, M. 2002. No trypanosoma lytic activity in sera of mice producing human
Sathiyaseelan, T., Naiman, B., Welte, S., MacHugh, N., Black, S.J. and Baldwin, C.L. 2002. Immunological characterization of a gamma delta T cell
Rogers, A.N., Welte, S., Black, S.J. and Baldwin, C.L. 2002. Genetic identification of homologues of CD72 and CD166/ALCAM, ligands for SRCR
Kitani, H., Black, S.J., Nakamura, Y., Naessens, J., Iraqi, F., Gibson, J., Murphy, N. and Yokomizo, Y. 2002. Recombinant tumor necrosis factor alpha
Baldwin, C.L., Black S.J. 2002. Immunology, In. Microbial Life. Eds.J.J. Jerry, J.T. Staley, S. Lory. Chapter 27, p 639-676. Sinauer Associates.
Black, S.J., N. Murphy, D. Nolan, 2001 Control of trypanosome parasitemia in Cape buffalo. Int. J. Parasitol. 31:562-565.
Black, S.J., N. B. Murphy, D. Nolan. 2001. Towards a trypanosomiasis vaccine. In: The African Trypanosomes, S,J. Black, J.R. Seed Eds. Pp.
Wu, H., Smyth, J., Luzzi, V., Fukami, K., Takenawa, T., Black, S.J., Allbriton, N.L. and Fissore, R.A. 2001. Sperm factor induces
Wang, Q., E. Hamilton and S. J. Black (2000). "Purine requirements for the expression of Cape buffalo serum trypanocidal activity." Comp Biochem Physiol C Toxicol Pharmacol 125(1): 25-32.
Black, S. J., Q. Wang, T. Makadzange, Y. L. Li, A. Van Praagh, M. Loomis and J. R. Seed (1999). "Anti-Trypanosoma brucei activity of nonprimate zoo sera." J Parasitol 85(1): 48-53.
Seed, J. R. and S. J. Black (1999). "A revised arithmetic model of long slender to short stumpy transformation in the African trypanosomes." J Parasitol 85(5): 850-4.
Wang, Q., N. Murphy and S. J. Black (1999). "Infection-associated decline of cape buffalo blood catalase augments serum trypanocidal activity." Infect Immun 67(6): 2797-803.
Black, S.J., Wang, Q., Makadzange, T., Li, Y-L., Van Praagh, A., Loomis, M. and Seed, J.R. (1998) Anti-Trypanosoma brucei activity of non-primate zoo sera. J. Parasitol., in press.
Muranjan, M., Wang, Q., Li, Y-l., Hamilton, E., Otieno-Omondi, F.P., Wang, J., Van Praagh, A., Grootenhuis, J.G. and Black, S.J. (1997) The trypanocidal Cape buffalo serum protein is xanthine oxidase. Infect. Immun. 65, 3806-3814.
Reduth, D., Grootenhuis, J.G., Olubayo, R.O., Maranjan, M., Otieno-Omondi, F.P., Morgan, G.A., Brun, R., Williams, D.J.L. and Black, S.J. (1994) African buffalo serum contains novel trypanocidal protein. J. Eukaryotic Microbiol. 41, 95-103.