Hui-Chen Hsu PhD

Dr. Hsu, Associate Professor of Medicine, studies the regulation of multiple types of immune cells in both humans and mice.  Dr. Hsu has had a long history of interest and experience in studying mechanisms of autoimmune disease.  She is the investigator who identified that autoimmune BXD2 mice exhibit unique features, including spontaneous formation of germinal centers, increased expression of activation-induced cytidine deaminase (AID), increased production of pathogenic autoantibodies that are polyreactive, significantly increased percentage of IL-17high CD4 TH cells (TH-17) and IL-17Rhigh B cells, and significantly increased numbers of type I interferon producing plasmacytoid dendritic cells in the spleens of these mice. 

Dr. Hsu has developed a two-tiered peptide microarray approach, coupled with epitope mapping of known autoantigens, to identify and characterize autoepitopes recognized by BXD2 autoreactive B cells.  Using this method, tetramers were prepared from two linear peptides derived from two ribonucleic acid binding proteins (RBP): lupus La and 70 kDa U1 small nuclear ribonucleoprotein (snRNP).  Dr. Hsu and colleagues have subsequently identified that there was reduction of transitional T1 B cells associated with a significantly higher frequency and greater numbers of RBP-reactive marginal zone precursor (MZ-P), transitional T3 and PDL-2+CD80+ memory B cells in BXD2 mice, compared to B6 mice. 

More recently, her collaboration with Dr. Mountz has led to a novel discovery that there was increased intracellular expression of IFN-β in B cells from a subset of African American SLE patients. She also applied the Fluidigm/BioMark based single cell RT-PCR strategy to identify the heterogeneity of B cells in expressing type I IFN genes versus IFN-stimulated genes (ISGs) in the transitional stage of B cells.

Education

• BS, Wen-Hwa University
• MS, Rutgers University
• PhD, Rutgers University

Research Interests

• Activation and activation-induced cell death (AICD) of T cells and immune mechanisms associated with T-cell senescence and other immune defects
• Spontaneous systemic autoimmunity in the BXD2 recombinant inbred mouse strain
• Unique cytokines mediate autoreactive B cell and T cell migration responses leading to development of pathogenic autoantibodies in BXD2 mice

Recent Publications

• Wang JH, New JS, Xie S, Yang PA, Wu Q, Li J, Luo B, Ding Y, Druey KM, Hsu H-C*, & Mountz JD. Extension of the germinal center stage of B-cell development promotes autoantibodies in BXD2 mice.   Arthritis & Rheum. 2013; 65(10): 2703-2712. (*co-senior author). PMCID: PMC3979745.
• Li H, Wu Q, Li J, Yang PA, Zhu Z, Buo B, Hsu H-C*, & Mountz JD.  Defective follicular exclusion of apoptotic antigens due to marginal zone macrophage defects in autoimmune BXD2 mice.  J Immunol (Cutting Edge). 2013; 190(9): 4465-4469. (*co-senior author). PMCID: PMC3656168.
• Ding Y, Li J, Wu Q, Yang P, Luo B, Xie S, Druey KM, Zajac AJ, Hsu H-C*, & Mountz JD. IL-17RA is essential for optimal localization of follicular T helper cells in the germinal center light zone to promote autoantibody-producing B cells.  J Immunol. 2013; 191: 1614-1624. (*co-senior author). PMCID: PMC3819396.
• Ding Y, Li J, Yang P, Zajac A, Hsu H-C*, Mountz JD. (2014) Interleukin-21 promotes germinal center reaction by skewing the follicular regulatory T cell to follicular helper T cell balance in autoimmune BXD2 mice.  Arthritis Rheumatol. 66(9):2601-12, 2014 (* co-senior author), PMCID: PMC4146687. 
• Li H, Fu Y-X, Wu Q, Zhou Y, Crossman DK, Yang PA, Li J, Luo B, Morel LM, Kabarowski JH, Yagita H, Ware C, Hsu H-C*, & Mountz JD. Interferon-induced defective mechanosensing impedes apoptotic cell clearance in lupus.  J Clin Investigation. 2015; 125(7): 2877-2890. (*co-senior author). PMCID: PMC4563689.