SCIENTISTS SPOTLIGHT

Xinbo Yang, PhD

Johnson & Johnson PsA Research Fellowship

Subject: Spondyloarthritis

Study Title: Exploiting Spondyloarthritis TCR:pHLA-B*27 Interaction for Therapeutic Development

My name is pronounced: Sheen-bo Yang

Biography:

I am a principal investigator at Sloan Kettering Institute, where I lead a group utilizing interdisciplinary approaches to understand autoimmune disease triggering at the molecular level. Before starting my lab, I performed postdoc research at Stanford University. During my postdoc time, I identified HLA-B*27 restricted T cell antigens that are involved with spondyloarthropathy (SpA) onset. My Ph.D. training in structural biology at University of Maryland enabled me to solve TCR-pHLA-B*27 complex structures, providing molecular mechanism on disease triggering. My research background in structural biology, protein engineering and T cell biology will enable my lab to understand pathogenesis of autoimmune diseases in-depth and leverage such information to develop specific and effective therapeutic agent for these diseases.

Research Summary:

Ankylosing Spondylitis (AS) and Acute Anterior Uveitis (AAU) belong to a group of disease termed as Spondyloarthropathies (SpA) which are highly prevalent with patients expressing human leukocyte antigen (HLA)-B*27. Such association has been documented for 50 years but the pathogenic role of HLA-B*27 involved in disease onset is not well understood. The primary role of HLA is to present a small piece of antigenic peptide for T cell recognition. T cells will then determine if this small piece of peptide is derived from self or foreign antigens. When T cells mis-recognize self as foreign antigen, autoimmunity will occur. Therefore, one of the hypotheses suggest that HLA-B*27 presents structurally similar peptides for pathogenic T cell recognition. However, it has been technically challenging to identify disease triggering peptides and only until recently we have provided evidence for the existence of such peptides. In addition, our work has provided the molecular mechanism to explain how pathogenic T cells are confused by self and foreign antigens. This work lays the foundation for subsequent high-throughput SpA related T cell antigen discovery and enable us to develop precise therapeutic agent.

Learn More:

https://www.mskcc.org/research/ski/labs/xinbo-yang

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