Back to Main

Faculty Detail    
Name HUI-CHEN HSU
 
Campus Address SHEL 311 Zip 2182
Phone 205-934-8909
E-mail rheu078@uab.edu
Other websites http://medicine.uab.edu/rheum/70690/
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Medicine  Med - Immunology/Rheumatology Associate Professor
Center  Arthritis & Musculoskeletal Diseases Center  Arthritis & Musculoskeletal Diseases Center Associate Professor
Center  Center for Aging  COMPREHENSIVE CTR FOR HEALTHY AGING Associate Professor

Graduate Biomedical Sciences Affiliations
Cell, Molecular, & Developmental Biology 
Immunology 
Pathobiology and Molecular Medicine 

Biographical Sketch 
Education
Chinese Culture University, Taipei, Taiwan BS 1986 Food Science and Nutrition
Rutgers University, New Brunswick, NJ MS 1990 Nutritional Sciences
Rutgers University, New Brunswick, NJ PhD 1995 Nutritional Sciences

HONORS AND AWARDS
1992 , Clinical Immunology Society Science Recognition Award for New Investigator in the 7th Annual Conference of Clinical Immunology; 1992, First Place for Excellence in Inflammation Research in C. Gordon Van Armon Award competition in the 6th International Inflammation Research Association Conference, 1992, Gina Finzi Memorial Student Summer Fellowship; Lupus Foundation of America, Inc; 1992, Second Prize Award for Excellence in Research in the Department of Medicine Annual Poster Symposium, UMDNJ-Robert Wood Johnson Medical School; 1993, Student Travel Award at the National Meeting of the American College of Rheumatology; 1994, Trainee Investigator Award for Excellence in Scientific Research in the National Meeting of American Federation of Clinical Research; 1995, Chapter Grant Recipient from Arthritis Foundation New Jersey Chapter; 1997, Post-postdoctoral Fellowship from Arthritis Foundation, 1999, Huang Foundation Trainee Award from American Association of Immunologists; 2001, Young Faculty Research Award from Southern Society for Clinical Investigation; 2003, First Place for UAB Center for Aging Scientific Program Abstract Competition: Biology of Aging Area.

Society Memberships
Organization Name Position Held Org Link
American Association of Anatomists     
American Association of Immunologists
 
   

Research/Clinical Interest
Title
The BXD2 autoimmune mouse model of lupus and erosive arthritis; Anti-DR5 as a novel therapy for lupus
Description
Two major studies are currently ongoing in my laboratory: 1. 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-17+ CD4 TH cells (TH-17) and IL-17R+ 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 interconnection of high IL-17, high type I IFN and the development of spontaneous germinal centers in these mice. 2. We are developing a new lupus mouse models to study the safety and efficacy of using an anti-human DR5 antibody (TRA-8) as novel therapy of lupus and other autoimmune diseases. Death receptor 5 (DR5) is a cell surface receptor for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Investigators at UAB (Dr. Tong Zhou and colleagues) have generated a unique anti-human DR5 antibody (TRA-8) that triggers the death of DR5+ cells. TRA-8 was selected due to its signaling of apoptosis (differing from TRAIL, which can induce proliferation). We have found that it kills cultured human lupus CD4+ T cells and plasma B cells. We have developed a transgenic mouse model that expresses a Floxed-STOP humanized DR5 mouse transgene (hu/mo DR5 Tg) and will express this hu/mo DR5 Tg in T and B cells in autoimmune mice that develop lupus-like disease. The ongoing project is to test the method of action and effectiveness of TRA-8 in depleting autoreactive CD4 T and plasma B cells, and its safety, in a special humanized mouse model, to determine its potential utility as a therapy for patients with lupus.

Selected Publications 
Publication PUBMEDID
Mountz JD, Li J, Hsu HC. Systemic autoimmunity caused by fas deficiency in macrophages: a new perspective on the first identified autoimmunity gene. Arthritis Rheum. 64:609-12, 2012  22139895 
Li J, Hsu HC, Yang P, Wu Q, Li H, Edgington LE, Bogyo M, Kimberly RP, Mountz JD. Treatment of arthritis by macrophage depletion and immunomodulation: testing an apoptosis-mediated therapy in a humanized death receptor mouse model. Arthritis Rheum 64:1098-109, 2012
 
22006294 
Hsu H-C, Yang PA, Wu Q, Wang J, Godwin J, Guentert T, Li J, Stockard CR, Le T, Chaplin DD, Grizzle WE, and Mountz, JD. Inhibition of the catalytic function of activation-induced cytidine deaminase (AICDA) promotes apoptosis of germinal center B cells. Arthritis Rheum 63:2038-48, 2011  21305519 
Mountz JD, Wang JH, Xie S, Hsu HC. Cytokine regulation of B-cell migratory behavior favors formation of germinal centers in autoimmune disease. Discov Med. 11:76-85, 2011  21276413 
Wang JH, Wu Q, Yang PA, Li H, Li J, Mountz JD and Hsu H-C. Type I IFN-dependent CD86high Marginal Zone-Precursor B Cells are Potent T-Cell Costimulators. Arthritis Rheum 63:1054-64, 2011  21225691 
Xie S, Hsu H-C, Wang J, Wu Q, Li H, Li J, d John D. Mountz. IL-17 activates the classical NF-kB signaling pathway to upregulate chemokine signal inhibitor molecules RGS16 in autoimmune B cells of BXD2 mice. The Journal of Immunology 184:2289-96, 2010.  20139273 
Wang JH, Li J, Wu Q, Yang P, Pawar RD, Xie S, Timares L, Raman C, Chaplin DD, Lu L, Mountz JD, Hsu HC. Marginal zone precursor B cells as cellular agents for Type I IFN-promoted antigen transport in autoimmunity. The Journal of Immunology 184:442-451, 2010.   19949066  
Xu X, Hsu H-C, Grizzle WE, Chatham WW, Wu Q, Stockard CR, Yang PA, Tunmire D, Holers M and Mountz JD. Increased expression of activation-induced cytidine deaminase (AID) is associated with anti-CCP and rheumatoid factor (RF) in rheumatoid arthritis (RA). Scan J Immunol 70:309-316, 2009.   19703021  
Hsu H-C, Yang PA, Wu Q, Riley M, Wang J, Chen J, Tousson A, Stanus AA, Le TV, Xu H, Lorenz RG, Kolls J, Carter RH, Chaplin D, Lu L, Williams RW and Mountz JD. Interleukin 17–producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice. Nature Immunol 9:166-175, 2008.   18157131 
Hsu H-C, Wu Y, Yang P, Wu Q, Fitzgerald A, Chen J, Job G, Wang J, Accatitti-Loper MA, Grizzle WE, Carter RH and Mountz JD. Over-expression of AID in B cells is associated with production of highly pathogenic autoantibodies. J Immunol 178:5357-5365, 2007.   17404321 
Hsu H-C, Zhou T, Kim H, Barnes S, Yang P-A, Wu Q, Zhou J, Freeman BA, Luo M and Mountz, JD. Production of a novel class of polyreactive pathogenic autoantibodies in BXD2 mice causes glomerulonephritis and arthritis. Arthritis Rheum 54:343-355, 2006.  16385526  
Mountz JD, Yang PA, Wu Q, Zhou J, Tousson A, Fitzgerald A, Allen J, Wang X, Cartner S, Grizzle WE, Yi N, Lu L, Williams RW and Hsu H-C. Genetic segregation of spontaneous erosive arthritis and generalized autoimmune disease in BXD2 recombinant inbred strain of mice. Scan J Immunol 61:128-138, 2005.  15683449 

Keywords
BXD2, lupus, arthritis, IL-17, type I IFN, DR5