Hui-Chen Hsu, PhD

University of Alabama, Birmingham, AL

2009 General Immune System Function, New Treatments

Deletion of lupus autoreactive cells using an anti-hDR5 antibody

Hui-Chen Hsu, PhDIn lupus, immune system cells are mistakenly activated, causing attack against otherwise healthy organs and tissues. Would selectively eliminating these activated cells help stop or slow the disease—without causing toxic effects and reducing overall immune system strength?

Dr. Hsu, an expert in using animal models of lupus, reports that activated cells commit suicide when the “TRA-8” antibody binds to “anti-human death receptor 5” (DR5). Few if any scientists have ever studied DR5 as a therapeutic target for accomplishing this—eliminating the specialized cells of the immune system (CD4 and B cells) that lead the charge against foreign pathogens and other invading micro-organisms.

Working with a specialized mouse model, Dr. Hsu and colleagues will test the effectiveness and safety of administering TRA-8 to reduce lupus-causing cells. If successful, she will launch her strategy for rapidly evaluating the approach in humans, through clinical trials.

Publication 2015

As reported by University of Alabama  at Birmingham (UAB), research partly funded by the LRI identified a mechanism that can lead to lupus.  The UAB team found that as billions of cells naturally die off every day, an autoimmune response can be triggered when macrophages do not keep the dying cells called apoptotic cells or ACs from entering the follicles of the spleen. Macrophages are a type of white blood cell that engulfs and digests foreign bodies. In a paper published in the Journal of Clinical Investigation, UAB investigators show how macrophages near the spleen can become too stiff to work properly, failing to prevent the dying cells from entering the follicles. Autoimmune antibodies form to attack the foreign bodies.

In an accompanying commentary in JCI, Drs. Claudia Mauri and Madhvi Menon, University College London write that, “The results of this study provide important insight into factors that inhibit AC clearance and promote the development of systemic lupus erythematosus.”

Select Publications

J Clin Invest. 2015 Jul 1;125(7):2877-90. Epub 2015 Jun 22. Interferon-induced mechanosensing defects impede apoptotic cell clearance in lupus. Li H, Fu YX, Wu Q, Zhou Y, Crossman DK, Yang P, Li J, Luo B, Morel LM, Kabarowski JH, Yagita H, Ware CF, Hsu HC, Mountz JD.