Jon P. Boyle

  • Associate Professor
  • Host-pathogen interaction

Contact

Office: (412) 624-5842
Lab: (412) 624-5842
102A Life Sciences Annex
4249 Fifth Avenue
Pittsburgh, PA 15260

Toxoplasma gondii is an intracellular pathogen that has infected over a billion people worldwide. This parasite sets up a chronic infection in its host that cannot be cured with currently available chemotherapies. Chronically infected humans that become immunocompromised due to HIV/AIDS are at high risk to develop severe toxoplasmosis that can lead to encephalitis and death.  Our long term goal is to identify factors in the parasite that are important in the host-pathogen interaction and have the potential to become new therapeutic or vaccine targets.  We do this using a variety of approaches.

Toxoplasma is closely related to other pathogens with a significant impact on human health, including the causative agents of malaria and cryptosporidiosis. What distinguishes Toxoplasma from these organisms is its incredible ability to infect a wide array of hosts, ranging from birds to humans.  We hypothesize that the genes underlying this unique feature play important roles in human infections.

These unique features of Toxoplasma bring up a number of important questions:

  1. What evolutionary events produced a parasite species with such a broad host range and how has that impacted its global success?
  2. Why do different Toxoplasma strains have different levels of virulence and/or compatibility in different hosts?
  3. What is the link between host range expansion and pathogenesis?

Fig 1: Toxoplasma secretion is mediated by unique secretory organelles such as the rhoptries and dense granules

Fig 2: After invasion Toxoplasma takes up residence within the parasitophorous vacuole

We can now begin to directly address these questions based the recent identification of parasite effector proteins that determine virulence in the mouse model (e.g., Saeij et al., Science 2006; Reese et al., PNAS 2011). These effectors are proteins that are secreted from the parasite into the host cell both during (Fig 1) and after (Fig 2) invasion.  Understanding the mechanism of action these parasite effectors should yield new insights into the evolution of the host-pathogen relationship on the molecular level, and provide a basis for the development of more effective treatment regimens in human cases of toxoplasmosis.

Approaches: In our lab we exploit the genetic tractability of Toxoplasma to address these questions. We use gene knockouts and knockins to assess the role of key loci in parasite biology. We use microarrays on both host and parasite transcripts to identify genetic networks that are manipulated by the parasite.  We use comparative genomics and forward genetics to identify genes that are responsible for phenotypic differences in pathogenesis between strains.  We use proteomics to identify previously uncharacterized proteins that Toxoplasma secretes into the host cell. Finally we use well-developed in vivo models to determine the impact of these genes on parasite virulence.

E-mail Lab

English ED, Adomako-Ankomah Y, Boyle JP.&

English ED, Adomako-Ankomah Y, Boyle JP.  Secreted effectors in Toxoplasma gondii and related species: determinants of host range and pathogenesis? (2015)  Parasite Immunol. 37(3):127-40. doi: 10.1111/pim.12166.  

Wier GM, McGreevy EM, Brown MJ, Boyle JP.

Wier GM, McGreevy EM, Brown MJ, Boyle JP.  New Method for the Orthogonal Labeling and Purification of Toxoplasma gondii Proteins While Inside the Host Cell. (2015)  MBio 6(2). pii: e01628-14. doi: 10.1128/mBio.01628-14.

Walzer KA, Wier GM, Dam RA, Srinivasan AR

Walzer KA, Wier GM, Dam RA, Srinivasan AR, Borges AL, English ED, Herrmann DC, Schares G, Dubey JP, Boyle JP. Hammondia hammondi harbors functional orthologs of the host-modulating effectors GRA15 and ROP16 but is distinguished from Toxoplasma gondii by a unique transcriptional profile. Eukaryot Cell.  13(12):1507-18. doi: 10.1128/EC.00215-14. Epub 2014 Oct 3.

Adomako-Ankomah Y, Wier GM, Borges AL, Wand HE

Adomako-Ankomah Y, Wier GM, Borges AL, Wand HE and Boyle JP.  (2014) Differential locus expansion distinguishes Toxoplasmatinae species and closely related strains of Toxoplasma gondii.    MBio 5(1):e01003-13.

Walzer KA, Adomako-Ankomah Y, Dam RA, Herrmann

Walzer KA, Adomako-Ankomah Y, Dam RA, Herrmann DC, Schares G, Dubey JP, and Boyle JP. (2013) Hammondia hammondi, an avirulent relative of Toxoplasma gondii, has functional orthologs of known T. gondii virulence genes. Proc Natl Acad Sci U S A 110:7446-7451.

Feliu V, Vasseur V, Grover HS, Chu HH, Brown MJ

Feliu V, Vasseur V, Grover HS, Chu HH, Brown MJ, Wang J, Boyle JP, Robey EA, Shastri N, and Blanchard N. (2013) Location of the CD8 T cell epitope within the antigenic precursor determines immunogenicity and protection against the Toxoplasma gondii parasite. PLoS Pathog 9:e1003449.

Kamau ET, Srinivasan AR, Brown MJ, Fair MG, Car

Kamau ET, Srinivasan AR, Brown MJ, Fair MG, Caraher EJ, and Boyle JP. (2012) A focused small-molecule screen identifies 14 compounds with distinct effects on Toxoplasma gondii. Antimicrobial Agents & Chemotherapy 56:5581-5590.

Adomako-Ankomah Y, Wier GM, Boyle JP

Adomako-Ankomah Y, Wier GM, Boyle JP. Beyond the genome: Recent advances in Toxoplasma gondii functional genomics. Parasite Immunology. 2011 Jul 1. doi: 10.1111/j.1365-3024.2011.01312.x.

Reese, M.L., G.M. Zeiner, J.P. Saeil, J.C. Boot

Reese, M.L., G.M. Zeiner, J.P. Saeil, J.C. Boothroyd, and J.P. Boyle (2011) Polymorphic family of injected pseudokinases is paramount in Toxoplasma virulence. Proc. Natl. Acad. Sci., USA.  108:9625-30.

Kamau E, Meehan T, Lavine MD, Arrizabalaga G, M

Kamau E, Meehan T, Lavine MD, Arrizabalaga G, Mustata Wilson G, and Boyle J. (2011) A novel benzodioxole-containing inhibitor of Toxoplasma gondii growth alters the parasite cell cycle. Antimicrobial Agents & Chemotherapy 55:5438-5451.

Khaminets, A., J.P. Hunn, S. Konen-Waisman, Y.O

Khaminets, A., J.P. Hunn, S. Konen-Waisman, Y.O. Zhao, D. Preukschat, J. Coers, J.P. Boyle, Y.C. Ong, J.C. Boothroyd, G. Reichmann, and J.C. Howard (2010) Coordinated loading of IRG resistance GTPases on to the Toxoplasma gondii parasitophorous vacuole. Cell Microbiol 12:939-961

Bontell, I.L., N. Hall, K.E. Ashelford, J.P. Dubey, J.P. Boyle, J. Lindh, and J.E. Smith (2009) W

Bontell, I.L., N. Hall, K.E. Ashelford, J.P. Dubey, J.P. Boyle, J. Lindh, and J.E. Smith (2009) Whole genome sequencing of a natural recombinant Toxoplasma gondii strain reveals chromosome sorting and local allelic variants. Genome Biol 10:RR53

Boyle, J.P., and J.R. Radke (2009) A history of studies that examine the interactions of Toxo

Boyle, J.P., and J.R. Radke (2009) A history of studies that examine the interactions of Toxoplasma with its host cell: emphasis on in vitro models. Int J Parasitol 39:903-914

Boyle, J.P., J.P. Saeij, S.Y. Harada, J.W. Ajioka, and J.C. Boothroyd (2008) Expression quantitat

Boyle, J.P., J.P. Saeij, S.Y. Harada, J.W. Ajioka, and J.C. Boothroyd (2008) Expression quantitative trait locus mapping of Toxoplasma genes reveals multiple mechanisms for strain-specific differences in gene expression. Eukaryot. Cell 7:1403-1414

Saeij, J.P., S. Coller, J.P. Boyle, M.E. Jerome, M.W. White, and J.C. Boothroyd (2007) Toxopl

Saeij, J.P., S. Coller, J.P. Boyle, M.E. Jerome, M.W. White, and J.C. Boothroyd (2007) Toxoplasma co-opts host gene expression by injection of a polymorphic kinase homologue. Nature 445:324-327

Boyle, J.P., J.P. Saeij, and J.C. Boothroyd (2007) Toxoplasma gondii: inconsistent disse

Boyle, J.P., J.P. Saeij, and J.C. Boothroyd (2007) Toxoplasma gondii: inconsistent dissemination patterns following oral infection in mice. Exp. Parasitol. 116:302-305

Boyle, J.P., J.P. Saeij, M.D. Cleary, and J.C. Boothroyd (2006) Analysis of gene expression durin

Boyle, J.P., J.P. Saeij, M.D. Cleary, and J.C. Boothroyd (2006) Analysis of gene expression during development: lessons from the Apicomplexa. Microbes Infect. 8:1623-1630

Boyle, J.P., B. Rajasekar, J.P. Saeij, J.W. Ajioka, M. Berriman, I. Paulsen, D.S. Roos, L.D. Sibl

Boyle, J.P., B. Rajasekar, J.P. Saeij, J.W. Ajioka, M. Berriman, I. Paulsen, D.S. Roos, L.D. Sibley, M.W. White, and J.C. Boothroyd (2006) Just one cross appears capable of dramatically altering the population biology of a eukaryotic pathogen like Toxoplasma gondii. Proc. Natl. Acad. Sci., USA 103:10514-10519

Saeij, J.P., J.P. Boyle, S. Coller, S. Taylor, L.D. Sibley, E.T. Brooke-Powell, J.W. Ajiok

Saeij, J.P., J.P. Boyle, S. Coller, S. Taylor, L.D. Sibley, E.T. Brooke-Powell, J.W. Ajioka, and J.C. Boothroyd (2006) Polymorphic secreted kinases are key virulence factors in toxoplasmosis. Science 314:1780-1783

Hillyer, J.F., S.L. Schmidt, J.F. Fuchs, J.P. Boyle, and B.M. Christensen (2005) Age-associated m

Hillyer, J.F., S.L. Schmidt, J.F. Fuchs, J.P. Boyle, and B.M. Christensen (2005) Age-associated mortality in immune challenged mosquitoes (Aedes aegypti) correlates with a decrease in haemocyte numbers. Cell Microbiol. 7:39-51

Khan, A., S. Taylor, C. Su, A.J. Mackey, J. Boyle, R. Cole, D. Glover, K. Tang, I.T. Paulsen, M.

Khan, A., S. Taylor, C. Su, A.J. Mackey, J. Boyle, R. Cole, D. Glover, K. Tang, I.T. Paulsen, M. Berriman, J.C. Boothroyd, E.R. Pfefferkorn, J.P. Dubey, J.W. Ajioka, D.S. Roos, J.C. Wootton, and L.D. Sibley (2005) Composite genome map and recombination parameters derived from three archetypal lineages of Toxoplasma gondii. Nucleic Acids Res. 33:2980-2992
Dr. Boyle got his Ph.D. in 2003 with Dr. Timothy Yoshino at the University of Wisconsin-Madison, performed his Postdoctoral work with Dr. John Boothroyd at Stanford University, and joined the department in 2008.