Brian DeDecker

Research Associate

Photo of Brian DeDecker

Brian.DeDecker@Colorado.EDU
Phone: (303) 492-2712
EXT: 2-2712
LAB: 2-2257

Website

Lab

Office Location

GOLD A318

Education

Ph.D., Yale University, 1997

Biography

Research Interests:
We are interested in how the fates of neural stem cells are determined and maintained in the developing organism, particularly in glia. We are also developing technologies and methods for discovering drugs to treat autoimmune diseases by targeting class II MHC proteins.

Research Profile:
One area of study in the lab is how the fates of neural stem cells are determined and maintained, particularly in glial cells. Another area of interest is developing technologies to discover drugs that target class II MHC for autoimmune disease therapies.

Glial cells are essential for the support and maintenance of neurons, such as mylenating axons to allow rapid propagation of action potentials. Although supportive roles are an important aspect of glial cell function, additional functions for glia have been further appreciated in the last few years. Glia mediate many aspects of neural development including axon guidance, directing and mediating synapse function, controlling blood flow, and immune response. The study of genes required for gliogenesis also has implications for treating autoimmune disorders that target glia, such as multiple sclerosis, and for developing strategies towards the therapeutic regeneration of nervous tissue. Glia derived cells are also the major source of brain cancers such as gliomas and provide a logical target for therapies that could block aberrant glial cell growth.

We are pursuing two new factors that we have found to have a role in glial cell development. One is a membrane bound receptor-like protein that is required for neural stem cells to fully matures into functional glia and the other is an epigenetic process that is required for glial cell migration along the axon.

Another area of interest are the Class II MHC proteins that 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 molecular tools and new methods to develop an 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 to specifically target MHC alleles associated with autoimmune diseases and minimize side-effects associated with broad based immunosuppressants.

Selected Publications

Modifiers of notch transcriptional activity identified by genome-wide RNAi.
Mourikis, P, Lake, RJ, Firnhaber, CB, and DeDecker, BS BMC Dev Biol, 10:107. 2010

Noble metals strip peptides from class II MHC proteins.
De Wall, SL, Painter, C, Stone, JD, Bandaranayake, R, Wiley, DC, Mitchison, TJ, Stern, LJ, and DeDecker, BS Nat Chem Biol, 2(4):197-201. 2006

Structural distortion of p53 by the mutation R249S and its rescue by a designed peptide: implications for "mutant conformation".
Friedler, A, DeDecker, BS, Freund, SMV, Blair, C, Rudiger, S, and Fersht, AR J Mol Biol, 336(1):187-96. 2004

Allosteric drugs: thinking outside the active-site box.
DeDecker, BS Chem Biol, 7(5):R103-7. 2000

Hot-spot mutants of p53 core domain evince characteristic local structural changes.
Wong, KB, DeDecker, BS, Freund, SM, Proctor, MR, Bycroft, M, and Fersht, AR Proc Natl Acad Sci U S A, 96(15):8438-42. 1999

The crystal structure of a hyperthermophilic archaeal TATA-box binding protein.
DeDecker, BS, O'Brien, R, Fleming, PJ, Geiger, JH, Jackson, SP, and Sigler, PB J Mol Biol, 264(5):1072-84. 1996

More Publications by Brian DeDecker

Research Opportunities