Associate Professor of Medicine, HMS
Our laboratory studies the parasitic nematodes that cause lymphatic filariasis or “elephant legs” (Brugia malayi and Wuchereria bancrofti) and onchocerciasis or “river blindness” (Onchocerca volvulus). We focus on protective and pathogenic host immune responses to the parasites, on worm products that directly damage host tissues, and on signal transduction pathways that are essential for the development of the worms in the mammalian host and insect vectors.
Lymphatic filariasis and onchocerciasis are spectral diseases, with clinical manifestations that range from asymptomatic infections to chronic lymphatic obstruction, inflammation, skin atrophy and blindness. It is a long-standing concept that the qualitative and/or quantitative characteristics of an individual’s immune response to parasite antigens determine the clinical outcome of infection with filarial worms. We are testing this hypothesis by examining the recognition patterns of native and recombinant antigens by cells and sera from donors with different clinical manifestations of infection. We are also testing the alternative hypothesis that filarial disease is caused directly by parasite “toxins” independently of host immune responses to the parasites. The ultimate objective of these studies is to identify candidate antigens for vaccine development and parasite molecules with pathogenic potential. We are currently examining the effect of filarial products on the growth and function of endothelial cells that line lymph vessels containing the worms, and the possible role of parasite proteases in the pathogenesis of chronic skin and eye disease in onchocerciasis. We are also testing one recombinant antigen that is preferentially recognized by sera from putatively immune individuals as a possible transmission blocking vaccine. This antigen was recently cloned and shown to be a functional chitinase essential for the development of microfilariae into infective larvae within mosquito vectors.
We have recently shown that filarial worms respond to exogenous epidermal growth factor (EGF) of mammalian origin, which triggers phosphorylation of several parasite molecules, including a ras-related protein and stimulates the development of filarial larvae. We are currently cloning the filarial EGF receptor and other molecules participating in transduction of the EGF signal in the parasite. The ultimate objective of these studies is to identify molecular targets for the rational development of new antihelminthic drugs.
M.D., 1968, Free University of Brussels