Sigrid C. Roberts

Biography

Education: 2003 | Postdoctoral Fellowship, National Research Service Award, OHSU 2003 | Postdoctoral Training, Oregon Health & Science University 1997 | Postdoctoral Fellowship, Deutsche Forschungsgemeinschaft, Universitaet Konstanz, Germany 1994 | Doctor of Philosophy, Biochemistry, University of Iowa 1989 | Diplom, Biology (equivalent to Master of Science degree), Universitaet Oldenburg, Germany 1988 | Fulbright Fellowship 1988 | Master of Science, Biochemistry, University of Wyoming, Laramie

Research Interest

Areas of Research & Specialization: The overall objective of my research is to characterize and therapeutically validate the polyamine pathway of the protozoan parasite Leishmania, which causes devastating and often fatal diseases in humans worldwide. Polyamines are essential cations that are especially important for rapidly proliferating cells such as parasites. The polyamine biosynthetic pathway in Leishmania is essential for parasite survival and significantly disparate from the host’s mechanism of polyamine production. A variety of genetic, cell and molecular biology, as well as biochemical techniques are being used to dissect the pathway. In addition, in vitromacrophage infectivity studies and in vivo murine infectivity models are being utilized to assess the importance of the polyamine pathway for host-parasite interactions and infectivity. Previous research has focused on the role of ornithine decarboxylase (ODC) for parasite infectivity. Parasites missing this enzyme were generated by targeted gene replacement techniques and the LdDodc gene deletion mutants exhibited dramatically reduced infectivity in mice compared to wild type parasites. These studies have validated ODC as a potentialtherapeutic target. More recent research focuses on arginine metabolism in parasite infections. In Leishmania, arginase is a vital enzyme that converts the amino acid arginine to ornithine, which is then directly funneled into polyamine biosynthesis. Arginine is a key amino acid for two competing pathways in host macrophages: it can be converted to ornithine by the action of host arginase or alternatively to the potent anti-leishmanial agent nitric oxide by the inducible nitric oxide synthase. An increased activity of host arginase has been found associated with increased parasitemia and disease exacerbation, and inhibition of host arginase has been shown to reduce but not eradicate parasite numbers in infected macrophages and mice. Similarly, arginase deficient Leishmania parasites are still capable of eliciting an infection, albeit at lower levels than wild type parasites, suggesting that parasites are able to scavenge at least some ornithine from the host. Thus, it appears that both host arginase and parasite arginase play key roles in Leishmania infections and a dual inhibition of host and parasite arginase may be a novel therapeutic strategy for the treatment of leishmaniasis.