Patricia J. Johnson, Ph.D.

Distinguished Professor

310-206-0249

4610C MSB, 148906

Website

Affiliations

Professor, Microbiology, Immunology & Molecular Genetics
Member, Immunity, Microbes & Molecular Pathogenesis GPB Home Area

Research Interests

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. Our laboratory has focused on five aspects of trichomonad biology: organelle biogenesis & evolution, regulation of gene expression, drug resistance, host:parasite interactions and genomics. Our interdisciplinary research program merges 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
T.vaginalis is the most common non-viral sexually transmitted infection affecting ~275 million people/yr worldwide and 3.7 million in the US. In 2014 the CDC identified trichomoniasis, the infection caused by T. vaginalis, as one of the Neglected Parasitic Infections (NPIs) in the United States.

About T.vaginalis Infection:

  • Infections are often asymptomatic but those that are symptomatic often result in vaginitis, urethritis, or prostatitis 
  • Infection increases risk of HIV transmission
  • Long-term infections lead to severe consequences such as increased risk of cervical cancer, prostate cancer, pre-term birth, and infertility
For more info, visit the CDC Trichomoniasis Fact Sheet
About the parasite:
  • T.vaginalis is a flagellated, extracellular protozoan parasite
  • Attachment and cytolysis are important in pathogenesis
  • Surface and secreted proteins are implicated in host-pathogen interactions
Our Research

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

For a recent layperson synopsis of some of our recent research, see https://researchfeatures.com/2018/05/31/cellular-crosstalk-disease-pathogenesis/

Biography
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
Selected Publications

Chen, Y.P, Riestra, A.M., Rai, A.K. & JOHNSON, P. J. (2019) A novel cadherin-like protein mediates adherence to and killing of host cells by the parasite Trichomonas vaginalis. mBio 10 (3): DOI: 10.1128/mBio.00720-19.

 

Mercer, F & JOHNSON, P.J. (2018) Trichomonas vaginalis: pathogenesis, symbiont interactions and host cell immune responses. Trends in Parasitology 34: 683-693.

 

Chen, Y.P, Twu, O. & JOHNSON, P.J. (2018) Trichomonas vaginalis macrophage migration inhibitory factor mediates parasite survival during nutrient stress. mBio 9: DOI 10.1128/mBio.00910-18.

 

Nievas, Y.R., Vashisht, A.A., Corvi, M.M., Metz, S., JOHNSON, P.J., Wohlschlegel, J.W. & de Miguel, N. (2018) Protein palmitolylation plays an important role in Trichomonas vaginalis adherence. Mol Cell Proteomics. https://doi.org/10.1074/mcp.ra117.000018. PMID: 29444981

 

Mercer. F., Ng, S.H., Brown, T.M, Boatman, G. & JOHNSON, P.J. (2018) Neutrophils kill the parasite Trichomonas vaginalis using trogocytosis. PLoS Biology 16: e2003885. https://doi.org/10.1371/journal.pbio.2003885.

 

Janssen, B.D., Chen, Y-P., Molgora, B.M, Wang, S.E, Simoes Barbosa, A, & JOHNSON, P.J.(2018) CRISPR/Cas9-mediated gene modification and gene knock out in the human-infective parasite Trichomonas vaginalis. Scientific Reports 8:270, DOI:10.1038/S41598-017-18442-3.

 

Pachano, T., Nievas, Y.R., Lizarraga, A., JOHNSON, P.J., Strobl-Mazzulla, P.H. & de Miguel, N.

(2017) Epigenetics regulates transcription and pathogenesis in the parasite Trichomonas vaginalis. Cell Microbiol 19(6): doi: 10.1111/cmi.12716.

 

Marti M. & JOHNSON P.J. (2016) Emerging roles for extracellular vesicles in parasitic infections. Curr Op Microbiol 32: 66-70. PMID: 27208506.

 

Mercer F., Diala F.G., Chen Y-P., Molgora B.M., Ng S.H. & JOHNSON, P.J. (2016) Leukocyte lysis and cytokine induction by the human sexually transmitted parasite Trichomonas vaginalis. PLoS Neglected Trop Dis 10 (8): e0004913. PMCID 4986988.

 

Riestra A.M., Gandhi S., Sweredoski M.J., Moradian A., Hess S., Urban, S. & JOHNSON, P.J. (2015) A Trichomonas vaginalis Rhomboid Protease and Its Substrate Modulate Parasite Attachment and Cytolysis of Host Cells. PLoS Pathogens 11(12):e1005294. PMCID 4684317.

 

Twu, O. & JOHNSON, P. J. (2014) Parasite extracellular vesicles: mediators of intercellular communication. PLoS Pathogens 10(8): e1004289

 

Twu, O., Dessi, D., Vu, A, Mercer, F., Stevens, G.C., de Miguel, N., Rappelli, P., Cocco A.R., Clubb, R., Fiori, P.L., & JOHNSON, P.J. (2014) The T. vaginalis homolog of macrophage migration inhibitory factor induces prostate cell proliferation and inflammatory responses. Proceedings of the National Academy of Science USA 111: 8179-84.

 

Twu, O., de Miguel, N., Lustig, G., Stevens, G.C, Vashisht, A.A., Wohlschlegel, J.A. & JOHNSON, P.J. (2013) Trichomonas vaginalis Exosomes Deliver Cargo to Host Cells and Mediate Host:Parasite Interactions. PLoS Pathogens 9(7): e1003482.

 

Schneider, R.E., Brown, M.T., Shiflett, A.M., Dyall, S.D., Hayes, R.D, Xie, Y., Loo, J.A. & JOHNSON, P. J. (2011) The Trichomonas vaginalis hydrogenosome proteome is highly reduced relative to mitochondria, yet complex compared with mitosomes. Int. J. Parasitol. 41: 1421-34.

 

Ryan, C. M., Mehlert, A., Richardson, J. M., Ferguson, M. A. and JOHNSON, P. J. (2011) Chemical structure of Trichomonas vaginalis surface lipoglycan: a role for short galactose (b1-4/3) N-acetylglucosamine repeats in host cell interaction. J. Biol. Chem. 286: 40494-508.

 

Smith, A.J., Chudnovsky, L., Simoes-Barbosa, A., Delgadillo-Correa, M.G. Jonsson, Z.O., Wohlschlegel, J.A.& JOHNSON, P.J. (2011) Novel core promoter elements and a cognate transcription factor in the divergent unicellular eukaryote Trichomonas vaginalis. Mol. Cell Biol. 31: 1444-58.

 

Shiflett, A.M. & JOHNSON, P.J. (2010) Mitochondrion-related organelles in eukaryotic protists. Annu. Rev. Microbiol. 64: 409-29.

 

de Miguel, N., Lustig, G.,Twu, O.,Chattopadhyay, A.,Wohlschlegel, J. A. & JOHNSON, P. J. (2010) Proteome analysis of the surface of Trichomonas vaginalis reveals novel proteins and strain-dependent differential expression. Mol Cell Proteomics: 9: 1554-66.

 

Simoes-Barbosa, A., Hirt, R.P & JOHNSON, P.J. (2010) A metazoan/plant-like capping enzyme and cap modified nucleotides in the unicellular eukaryote Trichomonas vaginalis. PLoS Pathogens: 6 (7): e1000999.

 

Carlton, J.M., Hirt, R.P., Silva, J.C., Delcher, A.L., Schatz, M., Zhao, Q., Wortman, J.R., Bidwell, S.L., Alsmark, U.C., Besteiro, S., Sicheritz-Ponten, T., Noel, C.J., Dacks, J.B., Foster, P.G., Simillion, C., Van de Peer, Y., Miranda-Saavedra, D., Barton, G.J., Westrop, G.D., Muller, S., Dessi, D., Fiori, P.L., Ren, Q., Paulsen, I., Zhang, H., Bastida-Corcuera, F.D., Simoes-Barbosa, A., Brown, M.T., Hayes, R.D., Mukherjee, M., Okumura, C.Y., Schneider, R., Smith, A.J., Vanacova, S., Villalvazo, M., Haas, B.J., Pertea, M., Feldblyum, T.V., Utterback, T.R., Shu, C.L., Osoegawa, K., de Jong, P.J., Hrdy, I., Horvathova, L., Zubacova, Z., Dolezal, P., Malik, S.B., Logsdon, J.M., Jr., Henze, K., Gupta, A., Wang, C.C., Dunne, R.L., Upcroft, J.A., Upcroft, P., White, O., Salzberg, S.L., Tang, P., Chiu, C.H., Lee, Y.S., Embley, T.M., Coombs, G.H., Mottram, J.C., Tachezy, J., Fraser-Liggett, C.M., and JOHNSON, P.J. (2007) Draft genome sequence of the sexually transmitted pathogen Trichomonas vaginalis. Science 315: 207-212.

 

Vanacova, S., Yan, W., Carlton, J.M. and JOHNSON, P.J. (2005) Spliceosomal introns in the deep-branching eukaryote Trichomonas vaginalis. Proc. Natl. Acad. Sci. USA. 102: 4430-4435.

 

Dyall, S.D., Yan, W., Delgadillo-Correa, M.G., Lunceford, A., Loo, J.A., Clarke, C.F., and JOHNSON, P.J. (2004) Complex I proteins of non-mitochondrial origin in a hydrogenosomal oxidoreductase complex. Nature: 431: 1103-1107.

 

Dyall, S.D., Brown, M.T. and JOHNSON, P.J. (2004) Ancient invasions: from endosymbionts to organelles. Science: 304:253-257.

 

Schumacher, M.A., Lau, A.O.T, JOHNSON, P.J. (2003) Structural basis of core promoter recognition in a primitive eukaryote. Cell 115: 413-424.

 

Bradley, P.J., Lahti, C.J., Plümper, E. and JOHNSON, P.J.  (1997)  Targeting and translocation of proteins into the hydrogenosome of the protist Trichomonas: similarities with mitochondrial protein import.  EMBO J. 16: 3484-3493.

 

Bui, E.T.N., Bradley, P.J. and JOHNSON, P.J. (1996) A common evolutionary origin for mitochondria and hydrogenosomes. Proc. Natl. Acad. Sci. USA  93: 9651-9656.

 

Quon, D.V.K., Delgadillo, M.G., Khachi, A., Smale, S.T. and JOHNSON, P. J.  (1994) Similarity between a ubiquitous promoter in an ancient eukarytote and mammalian initiator elements.  Proc. Natl. Acad. Sci. USA 91: 4579-4583.