Yuhong YangResearch Associate Professor

College of Medicine
Department of Neurology

Biomedical Research Tower
460 W. 12th Ave., Room 0604
Columbus, Ohio 43210

Research Interests: Dr. Yang is interested in understanding molecule mechanisms that regulate CNS autoimmunity, with the goals of both identifying therapeutic targets and developing innovative therapies to treat patients. Using immunological and molecular approaches, she is focused on two questions:

  1. What are the major determinants that trigger inflammatory pathways in myelin-specific CD4 T cells in multiple sclerosis (MS)?
  2. How can we suppress the development and progression of CNS autoimmunity?

My lab has focused on the characterization of pathogenesis and the development of novel therapies for Multiple Sclerosis (MS), mainly by utilizing different approaches to inhibit effector function of pathogenic T effector cells (Teff) and/or to promote the development of T regulatory cells (Treg). Myelin-specific CD4 T cells play critical roles in the formation of acute MS lesions and disease progression. However, it is not well-understood what the major determinants of T cell encephalitogenicity are. We identified IL-6 as the cytokine essential for the development of encephalitogenic Th17 cells, which highlights the importance of IL-6 signaling pathway in T cell encephalitogenicity. Therefore, we have been focusing on developing novel therapeutic reagents targeting IL-6/STAT3 signaling pathway for MS treatment. We have successfully developed a novel small molecule STAT3 inhibitor prodrug that significantly suppresses disease development and progression in murine model of MS and shifts Teff:Treg balance of CD4 T cells from MS patients. We have also developed several lead compounds of novel IL-6 inhibitors that show capacity in suppressing effector function of myelin-specific CD4 T cells and promoting iTreg development of human CD4 T cells. In addition to Th17 cells, IFNg producing Th1 cells are highly encephalitogenic in murine model of MS and implicated in MS pathogenesis. Th1 and Th17 cells have distinct cytokine profiles, suggesting that there are molecules other than the signature cytokines regulate T cell encephalitogenicity. We have recently shown that immune checkpoint PD-1 is expressed at relatively low levels on encephalitogenic Tbet+/+ Th1 and IL-6/IL-23 induced Th17 cells compared with their non-encephalitogenic counterparts, namely T-bet-/- Th1 cells and TGFβ/IL-6 induced Th17 cells, respectively. This suggests that PD-1 signaling pathway maybe a common mechanism shared by latter two CD4+ T cell subsets to inhibit their effector function and pathogenic potential. Hence, interventions that promote PD-1 activation may be of therapeutic benefit in individuals with MS by shifting the Teff:Treg balance of autoreactive CD4 T populations in a direction that favors the maintenance of disease remission. We have been focusing our research on understanding the roles and molecular mechanisms by which PD-1 signaling regulates myelin-specific Teff and Treg cells as well as the development of CNS autoimmunity. 

Current research projects:

  1. Determine the primary causes of T cell encephalitogenicity and characterize their therapeutic potential. Autoreactive myelin-specific CD4 T-cells mediate the formation of acute MS lesson in CNS, and she would like to understand the role of different key molecules in regulating T cell encephalitogenicity.
  1. She is trying to determine if IL-7Rα and its inhibitory receptors such as PD-1 and LAG-3 can regulate the cell-intrinsic of effector functions of myelin-specific CD4 T cells.
  2. These molecules help to regulate T effector responses and play an important role in the development of autoimmune diabetes, but it is currently unclear whether they regulate myelin-specific CD4 T cells in CNS autoimmunity.
  3. She is trying to determine the role of Blimp-1 in regulating myelin-specific CD4 T cells during disease progression in the EAE model of MS. Myelin-reactive CD4 T cells from MS patients display a memory phenotype. In EAE, the activation and differentiation behavior of CD4 T helper cells has been well-characterized, but very little is known about the molecule mechanisms that regulate the later stage of T cell maturation—the memory formation and reactivation of memory myelin-specific CD4 T cells.
  4. She is interested at identifying the key molecule critical for the formation and reactivation of these memory T cells, which may lead to novel therapeutic targets. Blimp-1 plays a critical role in regulating terminal differentiation and memory formation of B cells and CD8 T cells and is a leading candidate in these studies.
  1. New MS therapies that target the IL-6/STAT3 signaling pathway. Current treatments for MS are only partially effective, and new drugs are needed. Dr. Yang's previous work has demonstrated that IL-6 is critical for the development of highly encephalitogenic Th17 cells during disease progression in EAE, an animal model of MS. Therefore, she is developing small molecule compounds that target the IL-6/STAT3 signaling pathway and testing their efficacy in the EAE model of MS and with T cells from MS patients.

Research techniques: Flow cytometry, ELISA, cell culture, siRNA transfection, RNA purification, real time PCR, EAE induction in mice.

Active Funding: NIH R01: Small molecule in vivo probe development targeting the IL-6/STAT3 pathway for potential multiple sclerosis therapy. National Institute Of Neurological Disorders And Stroke, 05/1/2015-04/30/2018

PubMed articles

Google scholar articles

MD: Medicine Tongji Medical University
MS: Molecular Biology Tongji Medical University

Research Fellow: Molecular Biology, UT Southwestern Medical Center
Research Fellow: Neuroimmunology, UT Southwestern Medical Center
Research Fellow" Neuroimmunology, The Ohio State University Wexner Medical Center

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