Our work is centered in the characterization of metabolic pathways in protozoan parasites. We work with Trypanosoma cruzi, Trypanosoma brucei, and Toxoplasma gondii. 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 ion homeostasis mechanisms and intracellular calcium and pH regulation, and their importance in 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 addition, a pathway that is also very important for the survival and fitness of these parasites is the isoprenoid pathway. Numerous molecules with important roles are the products of this pathway and their characterization in these parasites is far from finished.
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 concentration. 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 to be conserved from bacteria to man. In addition, we later found that these organelles contain large amounts of phosphate in the form of polyphosphate (poly P). This led us to start projects to study the metabolism of poly P. Considering that these organelles contain high levels of poly P, 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.