My laboratory has three major interests. The first
two focus on defining the biology of the host-parasite relationship
for global parasitic infections like schistosomiasis and trypanosomiasis.
We are studying mechanisms by which parasites invade host tissue,
metabolize host proteins like hemoglobin, and regulate the expression
of virulence factors during different stages of their life cycle.
A tangent of this research is the development of specific inhibitors
targeting proteases necessary for parasitic invasion and metabolism.
We are also defining the host immune response to schistosome parasites
that results in granuloma formation and fibrosis. One particularly
intriguing discovery has been that schistosomes exploit the immune
response as a signal for growth and egg production. Our third area
of interest is the role of proteases in tumor progression. We are
evaluating the expression of proteases in both mouse models of tumor
development and in actual human tumor specimens. We then map structure-function
relationships in tumor proteases with the goal of designing specific
inhibitors as tools to probe the role of proteases in tumor progression,
and as leads for future chemotherapy. |
Wang SX, Pandey KC, Somoza JR, Sijwali PS, Kortemme T, Brinen LS, Rosenthal PJ, and McKerrow JH. Structural Basis for Unique Mechanisms of Folding and Hemoglobin Binding by a Malarial Protease. PNAS. In Press, 2006.
Mackey ZB, O’Brien TC, Greenbaum DC, Blank RB, McKerrow JH. A cathepsin B-like protease is required for host protein degradation in Trypanosoma brucei. JBC 12:279(46)48426-33,2004.
Davies, SJ, Grogan J, Blank R, Lim KC, Lockley
R, and McKerrow JH. Modulation of bloodfluke development in the
liver by unconventional CD4+ hepatic CD4 lymphocytes. Science. 294:1358-1361,
2001
information last updated June 2006 |