Toxoplasma modulates signature pathways of human epilepsy, neurodegeneration & cancer

Huân M. Ngô, Ying Zhou, Hernan Lorenzi, Kai Wang, Taek-Kyun Kim, Yong Zhou, Kamal El Bissati, Ernest Mui, Laura Fraczek, Seesandra V. Rajagopala, Craig W. Roberts, Alexandre Montpetit, Jenefer M. Blackwell, Sarra E. Jamieson, Kelsey Wheeler, Ian J. Begeman, Carlos Naranjo-Galvis, Ney Alliey-Rodriguez, Roderick G. Davis, Liliana Soroceanu & 11 others Charles Cobbs, Dennis A. Steindler, Kenneth Boyer, A. Gwendolyn Noble, Charles N. Swisher, Peter T. Heydemann, Peter Rabiah, Shawn Withers, Patricia Soteropoulos, Leroy Hood, Rima McLeod

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

One third of humans are infected lifelong with the brain-dwelling, protozoan parasite, Toxoplasma gondii. Approximately fifteen million of these have congenital toxoplasmosis. Although neurobehavioral disease is associated with seropositivity, causality is unproven. To better understand what this parasite does to human brains, we performed a comprehensive systems analysis of the infected brain: We identified susceptibility genes for congenital toxoplasmosis in our cohort of infected humans and found these genes are expressed in human brain. Transcriptomic and quantitative proteomic analyses of infected human, primary, neuronal stem and monocytic cells revealed effects on neurodevelopment and plasticity in neural, immune, and endocrine networks. These findings were supported by identification of protein and miRNA biomarkers in sera of ill children reflecting brain damage and T. gondii infection. These data were deconvoluted using three systems biology approaches: "Orbital-deconvolution" elucidated upstream, regulatory pathways interconnecting human susceptibility genes, biomarkers, proteomes, and transcriptomes. "Cluster-deconvolution" revealed visual protein-protein interaction clusters involved in processes affecting brain functions and circuitry, including lipid metabolism, leukocyte migration and olfaction. Finally, "disease-deconvolution" identified associations between the parasite-brain interactions and epilepsy, movement disorders, Alzheimer's disease, and cancer. This "reconstruction-deconvolution" logic provides templates of progenitor cells' potentiating effects, and components affecting human brain parasitism and diseases.

LanguageEnglish
Article number11496
Number of pages32
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 13 Sep 2017

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Toxoplasma
Epilepsy
Brain
Neoplasms
Congenital Toxoplasmosis
Parasites
Stem Cells
Biomarkers
Genes
Proteins
Neuronal Plasticity
Systems Biology
Smell
Toxoplasmosis
Movement Disorders
Brain Diseases
Proteome
Systems Analysis
MicroRNAs
Lipid Metabolism

Keywords

  • Toxoplasma gondii
  • congenital toxoplasmosis
  • human brain

Cite this

Ngô, H. M., Zhou, Y., Lorenzi, H., Wang, K., Kim, T-K., Zhou, Y., ... McLeod, R. (2017). Toxoplasma modulates signature pathways of human epilepsy, neurodegeneration & cancer. Scientific Reports, 7(1), [11496]. https://doi.org/10.1038/s41598-017-10675-6
Ngô, Huân M. ; Zhou, Ying ; Lorenzi, Hernan ; Wang, Kai ; Kim, Taek-Kyun ; Zhou, Yong ; Bissati, Kamal El ; Mui, Ernest ; Fraczek, Laura ; Rajagopala, Seesandra V. ; Roberts, Craig W. ; Montpetit, Alexandre ; Blackwell, Jenefer M. ; Jamieson, Sarra E. ; Wheeler, Kelsey ; Begeman, Ian J. ; Naranjo-Galvis, Carlos ; Alliey-Rodriguez, Ney ; Davis, Roderick G. ; Soroceanu, Liliana ; Cobbs, Charles ; Steindler, Dennis A. ; Boyer, Kenneth ; Noble, A. Gwendolyn ; Swisher, Charles N. ; Heydemann, Peter T. ; Rabiah, Peter ; Withers, Shawn ; Soteropoulos, Patricia ; Hood, Leroy ; McLeod, Rima. / Toxoplasma modulates signature pathways of human epilepsy, neurodegeneration & cancer. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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Ngô, HM, Zhou, Y, Lorenzi, H, Wang, K, Kim, T-K, Zhou, Y, Bissati, KE, Mui, E, Fraczek, L, Rajagopala, SV, Roberts, CW, Montpetit, A, Blackwell, JM, Jamieson, SE, Wheeler, K, Begeman, IJ, Naranjo-Galvis, C, Alliey-Rodriguez, N, Davis, RG, Soroceanu, L, Cobbs, C, Steindler, DA, Boyer, K, Noble, AG, Swisher, CN, Heydemann, PT, Rabiah, P, Withers, S, Soteropoulos, P, Hood, L & McLeod, R 2017, 'Toxoplasma modulates signature pathways of human epilepsy, neurodegeneration & cancer' Scientific Reports, vol. 7, no. 1, 11496. https://doi.org/10.1038/s41598-017-10675-6

Toxoplasma modulates signature pathways of human epilepsy, neurodegeneration & cancer. / Ngô, Huân M.; Zhou, Ying; Lorenzi, Hernan; Wang, Kai; Kim, Taek-Kyun; Zhou, Yong; Bissati, Kamal El; Mui, Ernest; Fraczek, Laura; Rajagopala, Seesandra V.; Roberts, Craig W.; Montpetit, Alexandre; Blackwell, Jenefer M.; Jamieson, Sarra E.; Wheeler, Kelsey; Begeman, Ian J.; Naranjo-Galvis, Carlos; Alliey-Rodriguez, Ney; Davis, Roderick G.; Soroceanu, Liliana; Cobbs, Charles; Steindler, Dennis A.; Boyer, Kenneth; Noble, A. Gwendolyn; Swisher, Charles N.; Heydemann, Peter T.; Rabiah, Peter; Withers, Shawn; Soteropoulos, Patricia; Hood, Leroy; McLeod, Rima.

In: Scientific Reports, Vol. 7, No. 1, 11496, 13.09.2017.

Research output: Contribution to journalArticle

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T1 - Toxoplasma modulates signature pathways of human epilepsy, neurodegeneration & cancer

AU - Ngô, Huân M.

AU - Zhou, Ying

AU - Lorenzi, Hernan

AU - Wang, Kai

AU - Kim, Taek-Kyun

AU - Zhou, Yong

AU - Bissati, Kamal El

AU - Mui, Ernest

AU - Fraczek, Laura

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AU - Jamieson, Sarra E.

AU - Wheeler, Kelsey

AU - Begeman, Ian J.

AU - Naranjo-Galvis, Carlos

AU - Alliey-Rodriguez, Ney

AU - Davis, Roderick G.

AU - Soroceanu, Liliana

AU - Cobbs, Charles

AU - Steindler, Dennis A.

AU - Boyer, Kenneth

AU - Noble, A. Gwendolyn

AU - Swisher, Charles N.

AU - Heydemann, Peter T.

AU - Rabiah, Peter

AU - Withers, Shawn

AU - Soteropoulos, Patricia

AU - Hood, Leroy

AU - McLeod, Rima

PY - 2017/9/13

Y1 - 2017/9/13

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KW - Toxoplasma gondii

KW - congenital toxoplasmosis

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