Professor and Barbara and Sanford Orkin/Georgia Research Alliance
Eminent Scholar, Department of Cellular Biology
350 B Paul D. Coverdell Center,
500 D.W. Brooks Drive
Athens, GA 30602
Member of the Editorial Board of Molecular and Biochemical Parasitology (1983-present), Experimental Parasitology (2005-present), and Antimicrobial Agents and Chemotherapy (2008-present); Editor of The Biochemical Journal (2005-present); Associate Editor of The Journal of Eukaryotic Microbiology (2004-present); Guest Editor of Acta Tropica (2002-2005), Microscopy and Microanalysis (2004), Experimental Parasitology (2008), and Essays in Biochemistry (2011).
Member of Faculty of 1000 (2006-present)
Corresponding Member, Brazilian Academy of Sciences (1999-present)
Burroughs Wellcome Fund New Initiatives in Malaria Research Award (1999-2001)
Burroughs Wellcome Fund/American Society for Microbiology Visiting Professor in the Microbiological Sciences (2000-2001)
Fellow of the American Academy of Microbiology (elected in 2010)
Fellow of the American Association for the Advancement of Science (elected in 2011)
|Acidocalcisomes (black granules) in a trypanosomatid|
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.
|Schematic representation of a typical acidocalcisome. Ca2+ uptake occurs in exchange for H+ by a reaction catalyzed by a vacuolar Ca2+-ATPase that is inhibited by vanadate. A H+ gradient is established by a bafilomycin A1-sensitive vacuolar H+-ATPase and an aminomethylenediphosphonate (AMDP)-sensitive vacuolar H+-PPase. Ca2+ release occurs in exchange for H+ and is favored by sodium-proton exchange. An aquaporin allows water transport. Other transporters (for Mg, Zn, Fe, Pi, PPi, Arginine, Lysine, etc) are probably present. The acidocalcisome is rich in pyrophosphate, short- and long-chain polyphosphate (poly P), magnesium, calcium, sodium, and zinc. An exopolyphophatase (PPX), a pyrophosphatase (PPase) and a poly P kinase (PPK) are also present. Not all these enzymes are necessarily present in all acidocalcisomes described and their internal composition may also vary (from Docampo et al. Nat. Rev. Microbiol. 3, 251-261, 2005).|
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Li, Z.H., Alvarez, V.E., De Gaudenzi, J.G., Sant'anna, C., Frasch, A.C., Cazzulo, J.J., Docampo, R. (2011) Hyperosmotic stress induces aquaporin-dependent cell shrinkage, polyphosphate synthesis, amino acid accumulation, and global gene expression changes in Trypanosoma cruzi. J. Biol. Chem. 286, 43959-43971.
Huang, G., Fang, J., Sant’Anna, C., Li, Z.-H., Wellems, D.L., Rohloff, P., and Docampo, R. (2011) Adaptor protein-3 (AP-3) complex mediates the biogenesis of acidocalcisomes and is essential for growth and virulence of Trypanosoma brucei. J. Biol. Chem. 286, 36619-36630
Docampo, R., and Moreno, S.N.J. (2011) Acidocalcisomes. Cell Calcium, 50, 113-119.
Docampo, R., Jimenez, V., King-Keller, S., Li, Z., and Moreno, S.N.J. (2011) The role of acidocalcisomes in the stress response of Trypanosoma cruzi. Adv. Parasitol. 75, 307-324.
Patel, S., and Docampo, R. (2010) Acidic calcium stores open for business: expanding the potential for intracellular Ca2+ signaling. Trends Cell Biol. 20, 277-286.
Patel, S., and Docampo, R. (2009) In with the TRP channels: intracellular functions for TRPM1 and TRPM2. Sci. Signal. 2 (95):pe69.
Ferella, M., Nilsson, D., Darban, J., Rodrigues, C.O., Bontempi, E.J., Docampo, R., Andersson, B. (2008) Proteomics in Trypanosoma cruzi - Localization of novel proteins to various organelles. Proteomics 8, 2735-2749.
Fang, J., Ruiz, F.A., Docampo, M., Luo, S., Rodrigues, J.C., Motta, L.S., Rohloff, P., and Docampo, R. (2007) Overexpression of a Zn2+-sensitive soluble exopolyphosphatase from Trypanosoma cruzi depletes polyphosphate and affects osmoregulation. J. Biol. Chem. 282, 32501-32510.
Smith, S.A., Mutch, N.J., Baskar, D., Rohloff, P., Docampo, R., and Morrissey, J.H. (2006) Polyphosphate modulates blood coagulation and fibrinolysis. Proc. Natl. Acad. Sci. U.S.A., 103, 903-908.
Docampo, R., de Souza, W., Miranda, K., Rohloff, P., and Moreno, S.N.J. (2005) Acidocalcisomes- conserved from bacteria to man. Nat. Rev. Microbiol. 3, 251-261.