The Endoplasmic Reticulum stress response and its role in disease

ER-stress

ER stress is a key molecular link in the pathology of numerus human diseases including metabolic syndrome, and protein misfolding diseases. In my research, I try to understand how this is possible and find new approaches for diagnosis/treatment.

ER chaperons, potential new therapeutic targets for common diseases

The endoplasmic reticulum (ER) can be seen as a cellular factory producing secretory proteins. There, strict quality-control systems are in place so that only correctly folded proteins can be transported to the final destinations. The ER machinery also encompasses real-time monitoring and clearance systems that constantly regulate its folding capacity via integrated signaling pathways.

The production of correctly folded proteins is essential for proper cell function and viability and subsequently for the health of the organism. 

Therefore, ER chaperones and signaling molecules have gained attention as potential therapeutic targets in various diseases, especially, those associated with protein misfolding (e.g. Amyloidosis, Alzheimer’s disease and Parkinson’s disease) and metabolic syndrome (e.g. type II diabetes, non-alcoholic fatty liver disease, obesity).

ERdj5, a unique ER chaperon protein

ERdj5 is an ER chaperon protein that our group has previously identified and described. It belongs to the Thioredoxin (Trx) superfamily and plays crucial roles in the ER functions. 

ERdj5 encompasses three distinctive features of chaperone proteins in one protein unit, namely; a DnaJ domain (an Hsp40 protein folding partner for BiP), three PDI-like domains (involved in the formation/isomerization of S-S bonds in new proteins), and one Trx-like domain (involved in reduction of S-S bonds in proteins).

Thus, ERdj5 is unique in a sense that, just as a single protein, it has the potential to perform a diverse range of chaperoning functions which would normally require two to three distinct chaperones.

Our current research

Given the multi-functional nature of ERdj5, our current research focuses on the role of ERdj5 in various diseases associated with protein misfolding and the metabolic syndrome. 

We apply multi-disciplinary approaches including histological techniques, cell culture and molecular biology approaches, and high throughput proteomic - bioinformatic analysis on clinical samples, animal models, and in vitro models. 

Our studies will lead to a better understanding of the metabolic imbalance in various diseases thereby potentially generating novel therapeutic targets.

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