Lupus: proteasome inhibitors and inflammation

Lupus: proteasome inhibitors and inflammation

Project details

Systemic lupus erythematosus (lupus) is a heterogeneous chronic autoimmune inflammatory disorder. Pathology is driven by plasma cells producing autoantibodies to host molecules, such as DNA. Because plasma cells produce large volumes of antibodies they are particularly dependent on the proteasome to maintain cellular homeostasis.  

Initial clinical trials using the proteasome inhibitor bortezomib to treat lupus were promising. However, follow-up studies revealed bortezomib treatment caused significant adverse reactions. Our lab has discovered that this was likely due to bortezomib triggered inflammation. 

This project aims to develop a cotreatment regime which will resolve the inflammation induced by proteasome inhibition in lupus. Students will investigate the effectivity of this therapeutic regime in an in vivo model of lupus using basic molecular techniques, flow cytometry and imaging.

About our research group

In the Masters laboratory we identify possible autoinflammatory disease causing mutations through clinical data. We investigate these mutations and the inflammatory pathways they activate using CRISPR/Cas9 genome editing,basic molecular biology techniques, flow cytometry,in vivo models and super-resolution imaging.

We also apply our findings to more complex autoinflammatory and autoimmune diseases. For example, by understanding how loss of proteasome function induces inflammation in the rare autoinflammatory disease proteasome associated autoinflammatory syndrome we may be able to improve proteasome inhibitor treatment of systemic lupus erythematosus. 

We maintain close links to industry and the clinic to make sure our discoveries can continue to have a direct effect on human health in the future. 

 

Email supervisors

 

Researchers:

Dr Sophia Davidson profile photo
Dr
Sophia
Davidson
Inflammation division

Project Type: