Tajie H. Harris

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Primary Appointment

Associate Professor, Neuroscience

Education

  • BS, Biology, Bemidji State University
  • PhD, Microbiology, University of Wisconsin-Madison
  • Postdoc, Immunoparasitology, University of Pennsylvania

Research Disciplines

Biophysics, Biotechnology, Immunology, Infectious Diseases/Biodefense, Microbiology, Neuroimmunology, Neuroscience

Research Interests

Immune response to infectious disease in the CNS

Research Description

Toxoplasma gondii is an intracellular, protozoan parasite that infects approximately one-third of the world population. The parasite can be acquired congenitally or in adults, through the ingestion of contaminated food or water. Acute infection with T. gondii leads to systemic disease that is largely controlled by the cytokine, IFN-g. Despite this, the parasite persists in several tissues, including the brain and retina, where an ongoing T cell-mediated immune response is necessary to limit parasite replication. The vast majority of infections are asymptomatic, but suppression of T cell function can lead to severe toxoplasmic encephalitis and/or retinochoroiditis. While the importance of T cells in controlling T. gondii in the brain and eye has been demonstrated, research in the Harris laboratory aims to identify factors within immune-privileged tissues that influence local resistance to T. gondii.
The Harris laboratory will use MP microscopy and other cutting-edge techniques to provide insight into the orchestration of local immune responses in the brain and retina. The laboratory is currently focusing on the role of microglia and macrophages in the control of infection in the brain. Several projects focus on the role of alarmins, which are molecules that are expressed by healthy cells and released into the tissue environment in response to aberrant death or damage.

Training

  • Basic Cardiovascular Research Training Grant
  • Biodefense & Infectious Diseases Short-Term Training to Increase Diversity in Biomedical Sciences
  • Biotechnology Training Grant
  • Global Biothreats Training Program
  • Infectious Diseases Training Program
  • Interdisciplinary Training Program in Immunology
  • Predoctoral Training in Neuroscience

Selected Publications

2023

Kovacs, M. A., Babcock, I. W., Marco, A. R., Sibley, L. A., Kelly, A. G., & Harris, T. H. (2024). Vascular Endothelial Growth Factor-C Treatment Enhances Cerebrospinal Fluid Outflow during Toxoplasma gondii Brain Infection but Does Not Improve Cerebral Edema. AMERICAN JOURNAL OF PATHOLOGY, 194(2), 225-237. doi:10.1016/j.ajpath.2023.11.008

2022

Kovacs, M. A., Cowan, M. N., Babcock, I. W., Sibley, L. A., Still, K., Batista, S. J., . . . Harris, T. H. (2022). Meningeal lymphatic drainage promotes T cell responses against Toxoplasma gondii but is dispensable for parasite control in the brain. ELIFE, 11. doi:10.7554/eLife.80775

Cowan, M. N., Kovacs, M. A., Sethi, I., Babcock, I. W., Still, K., Batista, S. J., . . . Harris, T. H. (2022). Microglial STAT1-sufficiency is required for resistance to toxoplasmic encephalitis. PLOS PATHOGENS, 18(9). doi:10.1371/journal.ppat.1010637

Shallberg, L. A. H., Phan, A. T. A., Christian, D. A. A., Perry, J. A., Haskins, B. E., Beiting, D. P., . . . Hunter, C. A. (2022). Impact of secondary TCR engagement on the heterogeneity of pathogen-specific CD8+ T cell response during acute and chronic toxoplasmosis. PLOS PATHOGENS, 18(6). doi:10.1371/journal.ppat.1010296

Cowan, M. N., Sethi, I., & Harris, T. H. (2022). Microglia in CNS infections: insights from Toxoplasma gondi and other pathogens. TRENDS IN PARASITOLOGY, 38(3), 217-229. doi:10.1016/j.pt.2021.12.004

2021

Noffsinger, B., Witter, A., Sheybani, N., Xiao, A., Manigat, L., Zhong, Q., . . . Purow, B. (2021). Technical choices significantly alter the adaptive immune response against immunocompetent murine gliomas in a model-dependent manner. JOURNAL OF NEURO-ONCOLOGY, 154(2), 145-157. doi:10.1007/s11060-021-03822-7

2020

Still, K. M., Batista, S. J., O'Brien, C. A., Oyesola, O. O., Fruh, S. P., Webb, L. M., . . . Harris, T. H. (2020). Astrocytes promote a protective immune response to brain Toxoplasma gondii infection via IL-33-ST2 signaling. PLOS PATHOGENS, 16(10). doi:10.1371/journal.ppat.1009027

Batista, S. J., Still, K. M., Johanson, D., Thompson, J. A., O'Brien, C. A., Lukens, J. R., & Harris, T. H. (2020). Gasdermin-D-dependent IL-1α release from microglia promotes protective immunity during chronic Toxoplasma gondii infection. NATURE COMMUNICATIONS, 11(1). doi:10.1038/s41467-020-17491-z

Kovacs, M. A., & Harris, T. H. (2020). Long-'Trm' protection of the CNS. NATURE IMMUNOLOGY, 21(8), 825-826. doi:10.1038/s41590-020-0716-3

Batista, S., Still, K., Johanson, D., Thompson, J., OâBrien, C., Lukens, J., & Harris, T. (2020). Gasdermin-D-dependent IL-1αrelease from microglia promotes protective immunity during chronicToxoplasma gondiiinfection. doi:10.1101/2020.01.22.915652

O'Brien, C. A., & Harris, T. H. (2020). ICOS-deficient and ICOS YF mutant mice fail to control Toxoplasma gondii infection of the brain. PLOS ONE, 15(1). doi:10.1371/journal.pone.0228251

2019

Webb, L. M., Oyesola, O. O., Fruh, S. P., Kamynina, L., Still, K. M., Patel, R. K., . . . Wojno, E. D. T. (2019). The Notch signaling pathway promotes basophil responses during helminth-induced type 2 inflammation. JOURNAL OF EXPERIMENTAL MEDICINE, 216(6), 1268-1279. doi:10.1084/jem.20180131

O'Brien, C. A., Batista, S. J., Still, K. M., & Harris, T. H. (2019). IL-10 and ICOS Differentially Regulate T Cell Responses in the Brain during Chronic Toxoplasma gondii Infection. JOURNAL OF IMMUNOLOGY, 202(6), 1755-1766. doi:10.4049/jimmunol.1801229

2018

Louveau, A., Herz, J., Alme, M. N., Salvador, A. F., Dong, M. Q., Viar, K. E., . . . Kipnis, J. (2018). CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature. NATURE NEUROSCIENCE, 21(10), 1380-+. doi:10.1038/s41593-018-0227-9

Norris, G. T., Smirnov, I., Filiano, A. J., Shadowen, H. M., Cody, K. R., Thompson, J. A., . . . Kipnis, J. (2018). Neuronal integrity and complement control synaptic material clearance by microglia after CNS injury. JOURNAL OF EXPERIMENTAL MEDICINE, 215(7), 1789-1801. doi:10.1084/jem.20172244

Still, K., Batista, S., OâBrien, C., Oyesola, O., Früh, S., Webb, L., . . . Harris, T. (2018). Astrocytes promote a protective immune response to brainToxoplasma gondiiinfection via IL-33-ST2 signaling. doi:10.1101/338400

2017

Klein, R. S., Voskuhl, R., Segal, B. M., Dittel, B. N., Lane, T. E., Bethea, J. R., . . . Cross, A. H. (2017). Speaking out about gender imbalance in invited speakers improves diversity. NATURE IMMUNOLOGY, 18(5), 475-478. doi:10.1038/ni.3707

O'Brien, C. A., Overall, C., Konradt, C., Hall, A. C. O., Hayes, N. W., Wagage, S., . . . Harris, T. H. (2017). CD11c-Expressing Cells Affect Regulatory T Cell Behavior in the Meninges during Central Nervous System Infection. JOURNAL OF IMMUNOLOGY, 198(10), 4054-4061. doi:10.4049/jimmunol.1601581

2016

Hidano, S., Randall, L. M., Dawson, L., Dietrich, H. K., Konradt, C., Klover, P. J., . . . Hunter, C. A. (2016). STAT1 Signaling in Astrocytes Is Essential for Control of Infection in the Central Nervous System. MBIO, 7(6). doi:10.1128/mBio.01881-16

Louveau, A., Smirnov, I., Keyes, T. J., Eccles, J. D., Rouhani, S. J., Peske, J. D., . . . Kipnis, J. (2016). Structural and functional features of central nervous system lymphatic vessels (vol 523, pg 337, 2015). NATURE, 533(7602). doi:10.1038/nature16999

2015

Louyeau, A., Harris, T. H., & Kipnis, J. (2015). Revisiting the Mechanisms of CNS Immune Privilege. TRENDS IN IMMUNOLOGY, 36(10), 569-577. doi:10.1016/j.it.2015.08.006

Louveau, A., Smirnov, I., Keyes, T. J., Eccles, J. D., Rouhani, S. J., Peske, J. D., . . . Kipnis, J. (2015). Structural and functional features of central nervous system lymphatic vessels. NATURE, 523(7560), 337-+. doi:10.1038/nature14432

Landrith, T. A., Harris, T. H., & Wilson, E. H. (2015). Characteristics and critical function of CD8+T cells in the Toxoplasma-infected brain. SEMINARS IN IMMUNOPATHOLOGY, 37(3), 261-270. doi:10.1007/s00281-015-0487-3

Cronk, J. C., Derecki, N. C., Ji, E., Xu, Y., Lampano, A. E., Smirnov, I., . . . Kipnis, J. (2015). Methyl-CpG Binding Protein 2 Regulates Microglia and Macrophage Gene Expression in Response to Inflammatory Stimuli. IMMUNITY, 42(4), 679-691. doi:10.1016/j.immuni.2015.03.013

Banigan, E. J., Harris, T. H., Christian, D. A., Hunter, C. A., & Liu, A. J. (2015). Heterogeneous CD8+ T Cell Migration in the Lymph Node in the Absence of Inflammation Revealed by Quantitative Migration Analysis. PLOS COMPUTATIONAL BIOLOGY, 11(2). doi:10.1371/journal.pcbi.1004058

2014

Rashighi, M., Agarwal, P., Richmond, J. M., Harris, T. H., Dresser, K., Su, M. -W., . . . Harris, J. E. (2014). CXCL10 Is Critical for the Progression and Maintenance of Depigmentation in a Mouse Model of Vitiligo. SCIENCE TRANSLATIONAL MEDICINE, 6(223). doi:10.1126/scitranslmed.3007811

Settles, E. W., Moser, L. A., Harris, T. H., & Knoll, L. J. (2014). Toxoplasma gondii Upregulates Interleukin-12 To Prevent Plasmodium berghei-Induced Experimental Cerebral Malaria. INFECTION AND IMMUNITY, 82(3), 1343-1353. doi:10.1128/IAI.01259-13

2013

Notarangelo, F. M., Wilson, E. H., Horning, K. J., Thomas, M. A. R., Harris, T. H., Fang, Q., . . . Schwarcz, R. (2014). Evaluation of kynurenine pathway metabolism in Toxoplasma gondii-infected mice: Implications for schizophrenia. SCHIZOPHRENIA RESEARCH, 152(1), 261-267. doi:10.1016/j.schres.2013.11.011

Butler, N. S., Harris, T. H., & Blader, I. J. (2013). Regulation of immunopathogenesis during Plasmodium and Toxoplasma infections: more parallels than distinctions?. TRENDS IN PARASITOLOGY, 29(12), 593-602. doi:10.1016/j.pt.2013.10.002

2012

Hall, A. O., Beiting, D. P., Tato, C., John, B., Oldenhove, G., Lombana, C. G., . . . Hunter, C. A. (2012). The Cytokines Interleukin 27 and Interferon-γ Promote Distinct Treg Cell Populations Required to Limit Infection-Induced Pathology. IMMUNITY, 37(3), 511-523. doi:10.1016/j.immuni.2012.06.014

Harris, T. H., Banigan, E. J., Christian, D. A., Konradt, C., Wojno, E. D. T., Norose, K., . . . Hunter, C. A. (2012). Generalized Levy walks and the role of chemokines in migration of effector CD8+ T cells. NATURE, 486(7404), 545-U145. doi:10.1038/nature11098

Harris, J. E., Harris, T. H., Weninger, W., Wherry, E. J., Hunter, C. A., & Turka, L. A. (2012). A Mouse Model of Vitiligo with Focused Epidermal Depigmentation Requires IFN-γ for Autoreactive CD8+ T-Cell Accumulation in the Skin. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 132(7), 1869-1876. doi:10.1038/jid.2011.463

Rashighi, M., Agarwal, P., Harris, T. H., Deng, A., Hunter, C. A., & Harris, J. E. (2012). CXCL10, an IFN-γ-induced chemokine, is required for the development of depigmentation in a mouse model of vitiligo. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 132, S1. Retrieved from https://www.webofscience.com/

2011

Sansing, L. H., Harris, T. H., Welsh, F. A., Kasner, S. E., Hunter, C. A., & Kariko, K. (2011). Toll-like Receptor 4 Contributes to Poor Outcome after Intracerebral Hemorrhage. ANNALS OF NEUROLOGY, 70(4), 646-656. doi:10.1002/ana.22528

John, B., Ricart, B., Wojno, E. D. T., Harris, T. H., Randall, L. M., Christian, D. A., . . . Hunter, C. A. (2011). Analysis of Behavior and Trafficking of Dendritic Cells within the Brain during Toxoplasmic Encephalitis. PLOS PATHOGENS, 7(9). doi:10.1371/journal.ppat.1002246

Sansing, L. H., Harris, T. H., Kasner, S. E., Hunter, C. A., & Kariko, K. (2011). Neutrophil Depletion Diminishes Monocyte Infiltration and Improves Functional Outcome After Experimental Intracerebral Hemorrhage. INTRACEREBRAL HEMORRHAGE RESEARCH: FROM BENCH TO BEDSIDE, 111, 173-178. doi:10.1007/978-3-7091-0693-8_29

Norose, K., Kikumura, A., Luster, A. D., Hunter, C. A., & Harris, T. H. (2011). CXCL10 Is Required to Maintain T-Cell Populations and to Control Parasite Replication during Chronic Ocular Toxoplasmosis. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 52(1), 389-398. doi:10.1167/iovs.10-5819

Harris, J. E., Harris, T. H., Weninger, W., Wherry, E. J., Hunter, C. A., & Turka, L. A. (2011). A new mouse model of vitiligo with epidermal depigmentation reveals a critical role for IFN-gamma in autoreactive T cell homing to the skin. PIGMENT CELL & MELANOMA RESEARCH, 24(4), 808. Retrieved from https://www.webofscience.com/

2010

Tait, E. D., Jordan, K. A., Dupont, C. D., Harris, T. H., Gregg, B., Wilson, E. H., . . . Hunter, C. A. (2010). Virulence of Toxoplasma gondii Is Associated with Distinct Dendritic Cell Responses and Reduced Numbers of Activated CD8+ T Cells. JOURNAL OF IMMUNOLOGY, 185(3), 1502-1512. doi:10.4049/jimmunol.0903450

Harris, T. H., Wilson, E. H., Tait, E. D., Buckley, M., Shapira, S., Caamano, J., . . . Hunter, C. A. (2010). NF-κB1 contributes to T cell-mediated control of Toxoplasma gondii in the CNS. JOURNAL OF NEUROIMMUNOLOGY, 222(1-2), 19-28. doi:10.1016/j.jneuroim.2009.12.009