RNA-Mediated Control of the Immune System
   Roopa Thapar, Ph.D.

Our immune system is exceptionally fine-tuned to recognize pathogens and tissue damage, repair the damage, eliminate the pathogens, and control the inflammation leading to the normal recovery of damaged or infected tissue.   To do this, the immune system rapidly produces a number of molecules in a highly controlled and orchestrated fashion.  These proteins are called cytokines, chemokines, interleukins, and adhesion molecules.  These protein molecules can be either pro-inflammatory or anti-inflammatory and their levels are tightly controlled during various stages of the immune response.  While the initiation of the immune response results an increased production of several of these immunomodulatory molecules by enhancing their transcription (at the DNA level), the steady state levels of the pro- and anti-inflammatory mediators are controlled during inflammation by regulating the translation and decay (post-transcription) of the messenger RNA that encodes for these proteins.

Overall Goal of the Thapar Lab
Our laboratory is working towards understanding the fundamental mechanism by which the protein levels of these inflammatory mediators are regulated, so that we can target these pathways for drug therapy in inflammation and cancer.  De-regulation of the production of these cytokines and chemokines is commonly observed in inflammatory diseases such as auto-immune disorders, rheumatoid arthritis and inflammatory bowel disease.  In the long-term we hope that these studies will lead to a better understanding of the immune response during inflammation and to the design of new drugs to treat immunological disorders.        

Recent Studies (July 2009-present)
The Thapar Lab has recently identified a novel pathway that involves the assembly of a previously uncharacterized ribonucleoprotein complex on the messenger RNAs that encode for a number of cytokines and chemokines.  These complexes involve small non-coding “miRNAs” that have recently been found to be major players in control of genetic information.  The assembly of this complex facilitates the degradation of these mediators.   We are working to understand how this complex assembles, what the protein and RNA factors are, and solve structures for components of the macromolecular complex by NMR Spectroscopy and X-ray Crystallography.