Roberto Docampo

The Docampo Laboratory has a long-term interest in the chemotherapy of parasitic diseases. Early work on free radical metabolism led to the findings that antifungal azoles are effective agents against Trypanosoma cruzi, and that the mode of action and toxicity of the nitro compounds currently used against these parasites involved free radical intermediates. The lab interest shifted in the early 1990's to the study of calcium homeostasis in parasitic protists. These studies led to the discovery of the acidocalcisomes, acidic organelles rich in calcium and phosphorus that are conserved from bacteria to man (see figure) (http://news.bbc.co.uk/2/hi/science/nature/3003946.stm). For the last few years, the lab has focused on the functions of these organelles in a variety of cells, including trypanosomatids, malaria parasites, Chlamydomonas, Dictyostelium, bacteria, human platelets, and insect, chicken, and sea urchin eggs.

The Docampo lab also found that acidocalcisomes are rich in pyrophosphate and short- and long-chain polyphosphate and that polyphosphate has a variety of novel functions in eukaryotes, from an osmoregulatory function in trypanosomes to a potent procoagulant and antifibrinolytic action in human blood (http://pubs.acs.org/cen/news/84/i03/8403notw9.html). The discovery of high levels of pyrophosphate in the acidocalcisomes also led to the use of pyrophosphate analogs, currently used in the treatment of osteoporosis and other bone diseases (bisphosphonates), as potential chemotherapeutic agents against parasitic protists. Some of these bisphosphonates have been shown to produce radical cures in animal models of leishmaniasis (http://newsarchive.asm.org/aug00/topic1.asp)

More recently, the Docampo lab has investigated the role of another organelle, the contractile vacuole complex, in osmoregulation in trypanosomes. These studies can reveal targets for trypanocidal drugs and have a variety of therapeutic implications. The lab strategy is to search for metabolic pathways in parasites that may be essential for their survival but may not find an equivalent counterpart in the host. Thus, one could look for specific inhibitors of such metabolic activities as possible means of controlling the parasites without damaging the hosts.