Controlling Autoimmune Diseases Using Bifunctional Peptide Inhibitors (BPI)
Teruna Siahaan
Professor, The University of Kansas
The long-term objective of this project is to develop bifunctional peptide inhibitor (BPI) molecules for controlling autoimmune diseases such multiple sclerosis (MS), rheumatoid arthritis (RA), and type-1 diabetes (T1D). The short-term objectives of this project are to develop BPI molecules and evaluate their mechanisms of action in suppressing experimental allergic encephalomyelitis (EAE) in mice, an animal model for MS. The BPI molecule is a conjugate between an antigenic peptide to a cell adhesion peptide that are connected via a linker. PLP-BPI molecules have been shown to effectively suppress the progress of experimental allergic encephalomyelitis (EAE) in mice. The central hypothesis is that the BPI molecule simultaneously binds to major histocompatibility complex-II (MHC-II) and intercellular adhesion molecule-1 (ICAM-1) on antigen-presenting cells (APC) to inhibit the immunological synapse formation at the interface between T cells and APC. As a result, it alters T-cell differentiation from inflammatory to regulatory phenotypes. Currently, the potential mechanisms of action of BPI molecules are being investigated. The concept has been expanded to using CII-BPI and GAD-BPI to suppress RA and T1D, respectively, in the animal models.
Dr. Siahaan is a Professor and Associate Chair of the Department of Pharmaceutical Chemistry, The University of Kansas. He is currently the Program Director/Principal Investigator of the NIH Biotechnology Training Program at The University of Kansas supported by the National Institutes of General Medicines (NIGMS). He has been mentoring numerous undergraduate students, graduate students, postdoctoral fellows, and visiting scholars. Dr. Siahaan published 170 papers and 11 patents. Dr. Siahaan is a Fellow of the American Association of Pharmaceutical Scientists (AAPS). He received Lila and Madison Self Fellowship, Pfizer Fellowship, and 2013 Mentor of the Year Award from The University of Kansas. Recently, he was selected to receive the 2014 PhRMA Foundation Award in Excellence in Pharmaceutics.