Office Phone Number:
Mol. Sci. Bldg
Los Angeles, CA 90095
|Professor, Microbiology, Immunology & Molecular Genetics|
|Member, Immunity, Microbes & Molecular Pathogenesis GPB Home Area|
Research in Johnson laboratory is focused on the molecular and cellular biology of the unicellular parasite Trichomonas vaginalis. This eukaryotic microbe is responsible for the most prevalent, non-viral, sexually-transmitted infection worldwide and is the most common parasite found in the US population. An estimated 275 million people worldwide have the parasite, including about 3.7 million in the United States; in 2014 the Center for Disease Control identified trichomoniasis, the infection cased by T. vaginalis, as one of Neglected Parasitic Infections (NPIs) in the United States. Beyond its medical importance, T. vaginalis is a fascinating organism for conducting research on the evolution of key biological processes present in all eukaryotes; from microbes to man. The precise evolutionary history of the trichomonad lineage is still debated; nevertheless, molecular data reveal T.vaginalis as one of the most divergent eukaryotes studied to date, making it an excellent system for exploring both biological diversity and extreme conservation. These basic science studies dovetail readily with medically important aspects of T. vaginalis, as its divergent, atypical properties offer possible chemotherapeutic targets and vaccine candidates. Over the years, our laboratory has focused on five aspects of trichomonad biology: organelle biogenesis & evolution, regulation of gene expression, drug resistance, host:parasite interactions and genomics. Systems used to explore unique properties of this human pathogen range from in vitro studies of protein targeting and organelle biogenesis to the analysis of genetically manipulated parasites and their interaction with host-derived cell lines, to obtaining the complete sequence of the T. vaginalis genome. Our interdisciplinary research program has merged several disciplines, including structural & cell biology, biochemistry, genomics, proteomics, bioinformatics, evolution and medical sciences. In recent years, we have narrowed our focus to defining and explaining critical pathogenic mechanisms that allow T. vaginalis to establish and maintain an infection. These studies include identifying parasite cell surface molecules that play a critical role in adherence and cytotoxicity to human epithelial cells and identifying host proteins that interact with the parasite and those that are modulated as a result of host:parasite interactions. Small vesicles, called exosomes, secreted by the parasite that appear to mediate cellular communication and assist in colonization of the host are also being characterized. We are also investigating a possible link between infection with T. vaginalis and prostate cancer; for news story see: http://www.bbc.com/news/health-27466853
Carlton, J.M., Hirt, R.P., Silva, J.C. - 60 other - J.C., Tachezy, J., Fraser-Liggett, C.M., and Johnson, P.J. Draft genome sequence of the sexually transmitted pathogen Trichomonas vaginalis. Science 2007; 315: 207-212.
Vanacova, S., Yan, W., Carlton, J.M. and Johnson, P.J. Spliceosomal introns in the deep-branching eukaryote Trichomonas vaginalis. Proc. Natl. Acad. Sci. USA 2005; 102: 4430-4435.
Dyall, SD Yan, W Delgadillo-Correa, MG Lunceford, A Loo, JA Clarke, CF Johnson, PJ Non-mitochondrial complex I proteins in a hydrogenosomal oxidoreductase complex. Nature. . 2004; 431(7012): 1103-7.
Dyall, SD Brown, MT Johnson, PJ Ancient invasions: from endosymbionts to organelles. Science. . 2004; 304(5668): 253-7.
Schumacher, MA Lau, AO Johnson, PJ Structural basis of core promoter recognition in a primitive eukaryote. Cell. . 2003; 115(4): 413-24.
Simoes-Barbosa Augusto, Hirt Robert P, Johnson Patricia J A metazoan/plant-like capping enzyme and cap modified nucleotides in the unicellular eukaryote Trichomonas vaginalis. PLoS pathogens. 2010; 6(7): e1000999.
de Miguel Natalia, Lustig Gil, Twu Olivia, Chattopadhyay Arnab, Wohlschlegel James A, Johnson Patricia J Proteome analysis of the surface of Trichomonas vaginalis reveals novel proteins and strain-dependent differential expression. Molecular & cellular proteomics : MCP. 2010; 9(7): 1554-66.
Twu Olivia, de Miguel Natalia, Lustig Gila, Stevens Grant C, Vashisht Ajay A, Wohlschlegel James A, Johnson Patricia J Trichomonas vaginalis exosomes deliver cargo to host cells and mediate hostâ¶parasite interactions. PLoS pathogens. 2013; 9(7): e1003482.
Shiflett April M, Johnson Patricia J Mitochondrion-related organelles in eukaryotic protists. Annual review of microbiology. 2010; 64(7): 409-29.
Lustig Gila, Ryan Christopher M, Secor W Evan, Johnson Patricia J Trichomonas vaginalis contact-dependent cytolysis of epithelial cells. Infection and immunity. 2013; 81(5): 1411-9.
Simoes-Barbosa Augusto, Louly Camila, Franco OctÃ¡vio L, Rubio Mary A, Alfonzo Juan D, Johnson Patricia J The divergent eukaryote Trichomonas vaginalis has an m7G cap methyltransferase capable of a single N2 methylation. Nucleic acids research. 2008; 36(21): 6848-58.
de Miguel Natalia, Riestra Angelica, Johnson Patricia J Reversible association of tetraspanin with Trichomonas vaginalis flagella upon adherence to host cells. Cellular microbiology. 2012; 14(12): 1797-807.
Simoes-Barbosa Augusto, Chakrabarti Kausik, Pearson Michael, Benarroch Delphine, Shuman Stewart, Johnson Patricia J Box H/ACA snoRNAs are preferred substrates for the trimethylguanosine synthase in the divergent unicellular eukaryote Trichomonas vaginalis. RNA (New York, N.Y.). 2012; 18(9): 1656-65.
Ryan Christopher M, Mehlert Angela, Richardson Julia M, Ferguson Michael A J, Johnson Patricia J Chemical structure of Trichomonas vaginalis surface lipoglycan: a role for short galactose (Î²1-4/3) N-acetylglucosamine repeats in host cell interaction. The Journal of biological chemistry. 2011; 286(47): 40494-508.
Schneider Rachel E, Brown Mark T, Shiflett April M, Dyall Sabrina D, Hayes Richard D, Xie Yongming, Loo Joseph A, Johnson Patricia J The Trichomonas vaginalis hydrogenosome proteome is highly reduced relative to mitochondria, yet complex compared with mitosomes. International journal for parasitology. 2011; 41(13-14): 1421-34.
Smith Alias J, Chudnovsky Lorissa, Simoes-Barbosa Augusto, Delgadillo-Correa Maria G, Jonsson Zophonias O, Wohlschlegel James A, Johnson Patricia J Novel core promoter elements and a cognate transcription factor in the divergent unicellular eukaryote Trichomonas vaginalis. Molecular and cellular biology. 2011; 31(7): 1444-58.
Ryan Christopher M, de Miguel Natalia, Johnson Patricia J Trichomonas vaginalis: current understanding of host-parasite interactions. Essays in biochemistry. 2011; 51(7): 161-75.
Twu Olivia, DessÃ Daniele, Vu Anh, Mercer Frances, Stevens Grant C, de Miguel Natalia, Rappelli Paola, Cocco Anna Rita, Clubb Robert T, Fiori Pier Luigi, Johnson Patricia J Trichomonas vaginalis homolog of macrophage migration inhibitory factor induces prostate cell growth, invasiveness, and inflammatory responses. Proceedings of the National Academy of Sciences of the United States of America. 2014; .
Wexler-Cohen Yael, Stevens Grant C, Barnoy Eran, van der Bliek Alexander M, Johnson Patricia J A dynamin-related protein contributes to Trichomonas vaginalis hydrogenosomal fission. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2014; 28(3): 1113-21.
Leitsch David, Janssen Brian D, Kolarich Daniel, Johnson Patricia J, DuchÃªne Michael Trichomonas vaginalis flavin reductase 1 and its role in metronidazole resistance. Molecular microbiology. 2014; 91(1): 198-208.