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HANS 309

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The immune system is comprised of a variety of cell types that work in a highly organized fashion to protect the body from infection and minimize tumor formation. This organizational process is largely carried out by the adaptive immune system with CD4 + T helper (Th) cells acting to trigger inflammation during infection and also suppress unwanted immune responses to non-harmful stimuli (i.e. allergens, food or normal body microflora). The dual nature (i.e. activator and suppressor) of Th cells is possible due to their unique ability to sense the environment and change their function based on these environmental cues.

Autoimmune disease occurs when the balance between the inflammatory and regulatory functions of Th cells is disrupted, resulting in excess inflammation that alters physiological processes. Inflammatory bowel disease (IBD) and graft-versus-host disease (GVHD) are two forms of intestinal autoimmune disease and are characterized by the accumulation of highly reactive inflammatory T cells in the intestines. However, the exact mechanisms by which inflammatory Th cells arise during inflammation and cause disease are unclear.

In the Olson lab, our goal is to better understand how CD4 + T helper cells drive intestinal inflammation by addressing these key questions:

  1. What signals drive the generation of pathogenic/inflammatory Th cells in the intestines?
  2. How do pathogenic/inflammatory T helper cells contribute to disease?
  3. Can we therapeutically target factors that drive the generation of pathogenic T helper cells or their functional byproducts to eliminate or reduce disease?

My laboratory uses a combination of cell and molecular biology approaches to examine signaling pathways associated with T helper cell differentiation. We also utilize pre-clinical models of disease, and high throughput culturing and RNA/protein profiling techniques to identify disease mechanisms and novel mediators of inflammation.



Yan, B., S. Chakravorty, C. Mirabelli, L. Wang, J. L. Trujillo-Ochoa, D. Chauss, D. Kumar, M. S. Lionakis, M. R. Olson , C. E. Wobus, B. Afzali, and M. Kazemian. 2021. 'Host-Virus Chimeric Events in SARS-CoV-2-Infected Cells Are Infrequent and Artifactual', J Virol , 95: e0029421.

Yan, B., T. Freiwald, D. Chauss, L. Wang, E. West, C. Mirabelli, C. J. Zhang, E. M. Nichols, N. Malik, R. Gregory, M. Bantscheff, S. Ghidelli-Disse, M. Kolev, T. Frum, J. R. Spence, J. Z. Sexton, K. D. Alysandratos, D. N. Kotton, S. Pittaluga, J. Bibby, N. Niyonzima, M. R. Olson , S. Kordasti, D. Portilla, C. E. Wobus, A. Laurence, M. S. Lionakis, C. Kemper, B. Afzali, and M. Kazemian. 2021. 'SARS-CoV-2 drives JAK1/2-dependent local complement hyperactivation', Sci Immunol , 6.

Canaria, D.A.; Yan, B.; Clare, M.G.; Zhang, Z.; Taylor, G.A.; Boone, D.L.; Kazemian, M.; Olson, M.R. 2021. 'STAT5 represses a STAT3-independent Th17-like program during Th9 cell differentiation', J Immunol , In Press.

Park, S., B. Griesenauer, H. Jiang, D. Adom, P. Mehrpouya-Bahrami, S. Chakravorty, M. Kazemian, T. Imam, R. Srivastava, T. A. Hayes, J. Pardo, S. C. Janga, S. Paczesny, M. H. Kaplan, and M. R. Olson . 2020. 'Granzyme A-producing T helper cells are critical for acute graft-versus-host disease', JCI Insight , 5.

Wang, L., J. Laing, B. Yan, H. Zhou, L. Ke, C. Wang, Y. Narita, Z. Zhang, M. R. Olson , B. Afzali, B. Zhao, and M. Kazemian. 2020. 'Epstein-Barr Virus Episome Physically Interacts with Active Regions of the Host Genome in Lymphoblastoid Cells', J Virol , 94.

Olson, M. R. , and M. H. Kaplan. 2019. 'TH9 immunodeficiency in patients with hyper-IgE syndrome', J Allergy Clin Immunol , 143: 935-36.

Chakravorty, S., B. Yan, C. Wang, L. Wang, J. T. Quaid, C. F. Lin, S. D. Briggs, J. Majumder, D. A. Canaria, D. Chauss, G. Chopra, M. R. Olson , B. Zhao, B. Afzali, and M. Kazemian. 2019. 'Integrated Pan-Cancer Map of EBV-Associated Neoplasms Reveals Functional Host-Virus Interactions', Cancer Res , 79: 6010-23.

DaSilva-Arnold, S. C., A. Thyagarajan, L. J. Seymour, Q. Yi, J. R. Bradish, M. Al-Hassani, H. Zhou, N. J. Perdue, V. Nemeth, A. Krbanjevic, A. P. M. Serezani, M. R. Olson , D. F. Spandau, J. B. Travers, M. H. Kaplan, and M. J. Turner. 2018. 'Phenotyping acute and chronic atopic dermatitis-like lesions in Stat6VT mice identifies a role for IL-33 in disease pathogenesis', Arch Dermatol Res , 310: 197-207.

Imam, T., S. Park, M. H. Kaplan, and M. R. Olson . 2018. 'Effector T Helper Cell Subsets in Inflammatory Bowel Diseases', Front Immunol , 9: 1212.

Olson, M. R. , B. J. Ulrich, S. A. Hummel, I. Khan, B. Meuris, Y. Cherukuri, A. L. Dent, S. C. Janga, and M. H. Kaplan. 2017. 'Paracrine IL-2 Is Required for Optimal Type 2 Effector Cytokine Production', J Immunol , 198: 4352-59.

Russ, B. E., M. Olshansky, J. Li, M. L. T. Nguyen, L. J. Gearing, T. H. O. Nguyen, M. R. Olson , H. A. McQuilton, S. Nussing, G. Khoury, D. F. J. Purcell, P. J. Hertzog, S. Rao, and S. J. Turner. 2017. 'Regulation of H3K4me3 at Transcriptional Enhancers Characterizes Acquisition of Virus-Specific CD8(+) T Cell-Lineage-Specific Function', Cell Rep , 21: 3624-36.

Ulrich, B. J., F. F. Verdan, A. N. McKenzie, M. H. Kaplan, and M. R. Olson . 2017. 'STAT3 Activation Impairs the Stability of Th9 Cells', J Immunol , 198: 2302-09.

Cheung, K. L., F. Zhang, A. Jaganathan, R. Sharma, Q. Zhang, T. Konuma, T. Shen, J. Y. Lee, C. Ren, C. H. Chen, G. Lu, M. R. Olson , W. Zhang, M. H. Kaplan, D. R. Littman, M. J. Walsh, H. Xiong, L. Zeng, and M. M. Zhou. 2017. 'Distinct Roles of Brd2 and Brd4 in Potentiating the Transcriptional Program for Th17 Cell Differentiation', Mol Cell , 65: 1068-80 e5.

Koh, B., M. M. Hufford, D. Pham, M. R. Olson , T. Wu, R. Jabeen, X. Sun, and M. H. Kaplan. 2016. 'The ETS Family Transcription Factors Etv5 and PU.1 Function in Parallel To Promote Th9 Cell Development', J Immunol , 197: 2465-72.

Olson, M. R. , F. F. Verdan, M. M. Hufford, A. L. Dent, and M. H. Kaplan. 2016. 'STAT3 Impairs STAT5 Activation in the Development of IL-9-Secreting T Cells', J Immunol , 196: 3297-304.

Olson, M. R. , B. Y. Chua, K. L. Good-Jacobson, P. C. Doherty, D. C. Jackson, and S. J. Turner. 2016. 'Competition within the virus-specific CD4 T-cell pool limits the T follicular helper response after influenza infection', Immunol Cell Biol , 94: 729-40.

Kaplan, M. H., M. M. Hufford, and M. R. Olson . 2015. 'The development and in vivo function of T helper 9 cells', Nat Rev Immunol , 15: 295-307.

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