Our work has centered in the characterization of metabolic pathways in protozoan parasites. We currently work with Trypanosoma cruzi, the etiologic agent of Chagas disease, and Trypanosoma brucei, which belongs to the group of parasites that cause sleeping sickness and Nagana. Our ultimate goal is to discover metabolic pathways in these parasites that may be essential for their survival but may not find an equivalent counterpart in their host. Thus, it would be possible to look for specific inhibitors of such metabolic activities as possible means of controlling the parasites without damaging the hosts. We study calcium homeostasis, and polyphosphate metabolism, and their importance for parasite physiology. We are also interested in signaling pathways since there is evidence that these pathways have important roles during the developmental cycle of these parasites. In particular, we became interested in the study of mitochondrial calcium transport and the role of mitochondria in autophagy and cell death. During the last several years, results from our laboratory led to the discovery of a novel organelle that we named the acidocalcisome, because it is acidic and contains a high calcium concentrations. We found this organelle in trypanosomes, Apicomplexan parasites, other unicellular eukaryotes, bacteria, and human cells. This was very important because it was the first organelle ever found as conserved from bacterial to human cells. In addition, we later found that these organelles contain large amounts of phosphate in the form of polyphosphate (polyP). This led us to start projects to study the metabolism of polyP. Considering that these organelles contain high levels of polyP, understanding the function of this polymer will lead us to understand the function of the acidocalcisome. One important enzyme that is present in the acidocalcisome is the vacuolar proton pyrosphosphatase. Since this enzyme is inhibited by pyrophosphate analogs (bisphosphonates) we thought that these compounds might inhibit parasite growth. This was in fact the case although we later found that the target for the action of many bisphosphonates is the isoprenoid pathway. We therefore started the characterization of this pathway. Bisphosphonates offer a potential new route to chemotherapy against parasitic diseases.
