Positions

Overview

  • 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-17 producing CD4 T helper cells.

    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 Drs Chatham and 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 currently applies the 10x Chromium-based transcriptomics/BCR analysis to identify mechanisms leading to B-cell tolerance loss at different checkpoints in SLE.

    • Selected Publications

    Research Overview

  • We have 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. We are currently studying the inter-connection of high IL-17, high type I IFN and the development of autoreactive B cells related to B-cell tolerance loss at the transitional stage and the germinal center stage in BXD2 mice.

    We currently study the close interaction between spleen marginal zone (MZ) B cells and MZ macrophages, and the implication of disrupting this close interaction in disease relapse following B-cell depletion therapy (BCDT) in systemic lupus erythematosus (SLE). In healthy individuals, the MZ B cells provide essential signals to maintain MZM survival and tolerogenic signaling to apoptotic debris derived autoantigens (AC-Ags) in the spleen MZ barrier. In SLE, a deficiency of tolerogenic MZMs occurs which disrupts the barrier and promotes an immunogenic environment including accumulation of uncleared AC-Ags and production of type I IFNs. Based on these results, we propose that BCDT in lupus, through depletion of the MZ B cells leads to a secondary depletion of the MZMs which may enable immunogenic responses to ACs in certain SLE patients. During deep B-cell depletion, when there are minimal B cells, this effect is not apparent. However, as B-cell repopulation occurs, the B cells are immediately subject to the immunogenic MZ microenvironment resulting in formation of autoreactive B cells and disease flares. We are currently developing strategies to overcome the loss of tolerogenic MZM barrier following BCDT with an ultimate goal to re-set B-cell tolerogenic state to achieve long-term remission. This work is currently supported by the Lupus Research Institute. http://lupusresearchinstitute.org/lupus-research/grant-recipients/hsu/hui-chen

    • Principal Investigator On

    Investigator On

    Education And Training

  • Doctor of Philosophy in Nutrition Sciences, Rutgers University : New Brunswick 1995

    • Full Name

  • Hui-Chen Hsu

    • Fax

  • 205-975-6648