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Immune Mechanisms of Disease Pathogenesis Laboratory

Photo of John S Yi, PhD

John S Yi, PhD

Office: 915 S. LaSalle Street, 204 SORF (Bldg. 41), Durham, NC 27710
Campus Mail: Box 2926, Durham, NC 27710
Phone: 919-684-4846

Scientific Focus

The Immune Mechanisms of Disease Pathogenesis laboratory, led by John S. Yi, Ph.D., is focused on developing a comprehensive understanding of the cell-mediated immune responses to diseases spanning from cancer to autoimmune diseases. This disease spectrum is an example of the benefits and consequences of the immune response and the critical balance that is required to achieve immune homeostasis. In my laboratory, we are deeply interested in how this balance in the immune response gets skewed in favor of autoimmunity or skewed in the opposite direction to elicit a strong immune response to eliminate pathogens without damaging the host.

In settings of chronic antigen stimulation, as in cancer or HIV, the immune response is inadequate and the T cells succumb to state known as “exhaustion,” which is a step-wise loss of function. Based on this observation in cancer, there is immense interest in checkpoint blockade therapy to restore the immune response. To profile the immune response, we utilize high dimensional flow cytometry and multiplex cellular assays to define the phenotype and functional capacity of immune cell subsets. Collectively, a clear understanding of the immunobiology of disease will greatly assist in identifying biomarkers or immune signatures that predict disease outcomes, treatment response, along with biomarkers that detect the onset of disease.

Key Projects Underway

  • Investigating the mechanisms of disease pathogenesis, mediated by B and T cells, in neuromuscular diseases including myasthenia gravis (MG), inclusion body myositis (IBM), and chronic inflammatory demyelinating polyneuropathy (CIDP).
  • Correlative T cell studies examining the effectiveness of checkpoint blockade therapy in patients with ovarian cancer and lung cancer.
  • Defining the role of CMV-specific CD8 T cells in lung transplant rejection. 
  • Understanding the composition of cellular infiltrates following rotational ankle fractures and identifying immunological signatures that predictive post-traumatic arthritis (PTA).

Selected Achievements

  • In the MuSK form of Myasthenia Gravis, we were the first group to demonstrate an increase in the frequency CD4 T cells producing the pro-inflammatory cytokine, IL-17.  We were also the first group to demonstrate lower frequencies of IL-10 producing B cells (B10).
  • Formed a repository for long-term storage of peripheral blood mononuclear cells (PBMC) and plasma from Myasthenia Gravis patients. This repository has grown into a multi-center repository from national and international sites. We have also expanded our collection to include other neuromuscular diseases.

Contact Us

John S. Yi, PhD

Latest Publications

Li, Yingkai, Jeffrey T. Guptill, Melissa A. Russo, James F. Howard, Janice M. Massey, Vern C. Juel, Lisa D. Hobson-Webb, et al. “Imbalance in T follicular helper cells producing IL-17 promotes pro-inflammatory responses in MuSK antibody positive myasthenia gravis.” J Neuroimmunol 345 (August 15, 2020): 577279.

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Yi, John S., Melissa A. Russo, Shruti Raja, Janice M. Massey, Vern C. Juel, Jay Shin, Lisa D. Hobson-Webb, Karissa Gable, and Jeffrey T. Guptill. “Inhibition of the transcription factor ROR-γ reduces pathogenic Th17 cells in acetylcholine receptor antibody positive myasthenia gravis.” Exp Neurol 325 (March 2020): 113146.

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Ezekian, Brian, Paul M. Schroder, Michael S. Mulvihill, Andrew Barbas, Bradley Collins, Kyle Freischlag, Janghoon Yoon, et al. “Pretransplant Desensitization with Costimulation Blockade and Proteasome Inhibitor Reduces DSA and Delays Antibody-Mediated Rejection in Highly Sensitized Nonhuman Primate Kidney Transplant Recipients.” J Am Soc Nephrol 30, no. 12 (December 2019): 2399–2411.

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Kwun, Jean, Marie Matignon, Miriam Manook, Soulef Guendouz, Vincent Audard, David Kheav, Elsa Poullot, et al. “Daratumumab in Sensitized Kidney Transplantation: Potentials and Limitations of Experimental and Clinical Use.” J Am Soc Nephrol 30, no. 7 (July 2019): 1206–19.

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