Brian DeDecker - Research Assistant Professor

We have two major focuses in the lab. One examines the influence that epigenetic factors have on the developmental signaling pathway Notch and the other is using class II MHC as a target for autoimmune disease therapies.

The term epigenetics describes an inheritable state that affects phenotypic outcomes, yet is not due to a DNA mutation. For instance, post-translational modifications on histones, the proteins that package DNA, are known to suppress and activate transcription and these marks are passed through cell divisions. The setting and erasing of these epigenetic marks on histones plays a major role in establishing a stem cell's identity and guiding its differentiation through development. We found in a genome wide RNAi screen that histone based epigenetic marks can regulate the transcriptional output of the developmental signaling pathway Notch. We are currently using drosophila as a developmental and biochemical model system to explore the relationship between histone modifications and developmental processes such as neurogenesis that are controlled by Notch signaling.

Class II MHC proteins normally present foreign peptides to T-cells resulting in an immune response. In some diseases, this process goes awry and the immune system attacks itself in what is known as an autoimmune response. Diseases such as juvenile diabetes and rheumatoid arthritis are two such examples. We developed and performed a high-throughput screen to search for small molecules that would inhibit such an autoimmune response by displacing peptides from the grip of a MHC class II protein. This work led us to the unexpected discovery that noble metals such as gold could strip peptides from class II MHC protein by an allosteric mechanism. This was intriguing, as gold has been used for many years to effectively treat rheumatoid arthritis. We are currently developing anti-autoimmune class of drugs that target class II MHCs by building on our discovery and utilizing the mechanism of noble metals. Such a drug would have the potential be targeted to specific MHC alleles associated with autoimmune diseases and be more effective in their treatment.