Toll-like receptor (TLR)/interleukin 1 receptor (IL-1R) signaling plays a critical pathogenic role in many forms of inflammatory and autoimmune diseases. Interruption of this signal transduction is a desirable therapeutic approach to these diseases.

Using the unique position and function of protein kinase D1 (PKD1), researchers at the University of Tennessee Health Science Center (UTHSC) have identified a peptide that inhibits the function of PKD1 in TLR/IL-1R signal transduction. The researchers now want to utilize this as a way to develop cell-permeable TLR/IL-1R pathway-specific PKD1 inhibitors. These inhibitors can suppress TLR/IL-1R-mediated inflammatory responses and have the potential to be a novel treatment approach to autoimmune diseases, such as rheumatoid arthritis.

Related publications:

• Kim, Y. I., Park, J. E., Brand, D. D., Fitzpatrick, E. A., and Yi, A. K. (2010) J Immunol 184, 3145-3156

• Park, J. E., Kim, Y. I., and Yi, A. K. (2009) J Immunol 182, 6316-6327

• Park, J. E., Kim, Y. I., and Yi, A. K. (2008) J Immunol 181, 2044-2055

Patents

A provisional application was filed March, 2013

The Inventor

Dr. Ae-Kyung Yi is an Associate Professor at the University of Tennessee Health Science Center. Her expertise is in cellular and molecular immunology with special focus on innate immunity and inflammation. Her research interests include signal transduction mechanisms of pattern recognition receptors, including Toll-like receptors and the interleukin 1 receptor, and the impacts of signaling modulators in the TLR/IL-1R pathway on the inflammatory process. Additional interests include the pathogenesis of chronic inflammatory diseases, including rheumatoid arthritis and hypersensitivity pneumonitis, and development of new therapeutic approaches by targeting signaling modulators in theTLR/IL-1R pathway.