We study tropical diseases currently focused on malaria, leptospirosis and brucellosis. We carry out fundamental investigations in La Jolla and translational aspects in Peru. Our malaria studies focus on molecular, cellular and biochemical mechanisms by which the malaria parasite (the ookinete)…
more stage invades the mosquito midgut. The long-term goal is to develop strategies of blocking malaria transmission from humans to mosquitoes. We have determined biochemical, cellular and molecular mechanisms by which ookinete-secreted proteins (chitinases, proteases, adhesion molecules) allow the parasite to penetrate the mosquito midgut. These studies define mechanisms of parasite transmission that can potentially be interfered with to prevent malaria transmission. Our laboratory has discovered a novel pathway of secretion in ookinetes relevant to the entire class of Apicomplexan parasites. He is currently leading efforts to translate these laboratory findings to the field setting in Peru in which he seeks to understand malaria transmission dynamics and to use human immune responses to guide malaria transmission-blocking vaccine target discovery. Our studies in leptospirosis use epidemiology, ecology, immunology and molecular taxonomy to understand fundamental, unexplored aspects of this zoonotic disease. We are asking why some patients with leptospirosis develop only inapparent infection or mild febrile disease, while others develop fulminant disease characterized by jaundice, renal failure, hemorrhage, and refractory shock. We recently developed a small animal model that demonstrates the critical role of innate immunity in protection from severe disease, and are translating these findings to the field context. We have expanded our studies to more generally study tropical bacterial zoonoses including brucellosis in a bench to bedside manner.
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