研究领域

In my research, I employ biochemical, molecular, and cellular approaches to explore physiology of trypanosomatid parasites (Trypanosoma brucei, Trypanosoma cruzi) using Crithidia fasciculata, a trypanosomatid parasite of mosquitoes, as a non-pathogenic model species. My research interests focus on two overarching questions : (1) How do trypanosomatids respond to cell volume (osmotic) stresses? (2) How are trypanosomatid proteins trafficked to subcellular compartments? The contractile vacuole apparatus of eukaryotic microorganisms has a clear role in cell volume regulation, yet its mechanism has remained elusive since the organelle was described many years ago. While not all trypanosomatids possess contractile vacuole apparatus, these complexes play an essential role in the physiology of human trypanosomatid pathogens including T. cruzi, the causative agent of Chagas’ disease. No non-toxic, effective drug treatment exists for diseases like T. cruzi. Contractile vacuole complexes are absent from higher eukaryotes, and this complex may represent a target for potential therapeutics. I previously localized a number of proteins to the contractile vacuole of T. cruzi, but the function of these proteins is largely unknown. Very little is known about protein trafficking in trypanosomatid parasites, and we are exploring mitochondrial protein targeting in Crithidia fasciculata. We have identified a sequence motif that may serve as a targeting signal for these parasites. Currently, we are developing strains of C. fasciculata that express GFP-fusion proteins carrying wild-type and mutant motifs as a means of determining the role of this motif in mitochondrial protein import.

Comparative Physiology and Biochemistry

近期论文

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Identification of contractile vacuole proteins in Trypanosoma cruzi. Ulrich PN, Jimenez V, Park M, Martins VP, Atwood J 3rd, Moles K, Collins D, Rohloff P, Tarleton R, Moreno SN, Orlando R, Docampo R. PLoS One. 2011 Mar 18;6(3):e18013. doi: 10.1371/journal.pone.0018013. Proteomic analysis of the acidocalcisome, an organelle conserved from bacteria to human cells. Huang G, Ulrich PN, Storey M, Johnson D, Tischer J, Tovar JA, Moreno SN, Orlando R, Docampo R. PLoS Pathog. 2014 Dec 11;10(12):e1004555. doi: 10.1371/journal.ppat.1004555. eCollection 2014 Dec. Evolution of acidocalcisomes and their role in polyphosphate storage and osmoregulation in eukaryotic microbes. Docampo R, Ulrich P, Moreno SN. Philos Trans R Soc Lond B Biol Sci. 2010 Mar 12;365(1541):775-84. doi: 10.1098/rstb.2009.0179. Review. The acidocalcisome vacuolar transporter chaperone 4 catalyzes the synthesis of polyphosphate in insect-stages of Trypanosoma brucei and T. cruzi. Ulrich PN, Lander N, Kurup SP, Reiss L, Brewer J, Soares Medeiros LC, Miranda K, Docampo R. J Eukaryot Microbiol. 2014 Mar-Apr;61(2):155-65. doi: 10.1111/jeu.12093. Epub 2014 Jan 3. Trypanosoma brucei vacuolar transporter chaperone 4 (TbVtc4) is an acidocalcisome polyphosphate kinase required for in vivo infection. Lander N, Ulrich PN, Docampo R. J Biol Chem. 2013 Nov 22;288(47):34205-16. doi: 10.1074/jbc.M113.518993. Epub 2013 Oct 10. Calcium- and polyphosphate-containing acidocalcisomes in chicken egg yolk. Ramos IB, Miranda K, Ulrich P, Ingram P, LeFurgey A, Machado EA, de Souza W, Docampo R. Biol Cell. 2010 Apr 9;102(7):421-34. doi: 10.1042/BC20100011. Target of rapamycin (TOR)-like 1 kinase is involved in the control of polyphosphate levels and acidocalcisome maintenance in Trypanosoma brucei. de Jesus TC, Tonelli RR, Nardelli SC, da Silva Augusto L, Motta MC, Girard-Dias W, Miranda K, Ulrich P, Jimenez V, Barquilla A, Navarro M, Docampo R, Schenkman S. J Biol Chem. 2010 Jul 30;285(31):24131-40. doi: 10.1074/jbc.M110.120212. Epub 2010 May 21. Prevalence of Perkinsus marinus (dermo), Haplosporidium nelsoni (MSX), and QPX in bivalves of Delaware's inland bays and quantitative, high-throughput diagnosis of dermo by QPCR. Ulrich PN, Ewart JW, Marsh AG. J Eukaryot Microbiol. 2007 Nov-Dec;54(6):520-6.