The ubiquitin proteasome system (UPS) plays a pivotal role in most cellular processes. Emerging data suggests roles for the UPS outside of the known housekeeping function in protein turnover, highlighting that more has to be done to understand the complex nature of the UPS and its functions in the cell. We study the UPS starting from basic cellular functions and progress towards understanding its involvement in human diseases, ranging from muscle atrophies to cancer. In addition, our efforts are concentrated on developing novel molecular, chemical, and biophysical technologies to gain insight into complex cellular processes.
A core focus we have with translational potential is to “hijack” the UPS for targeted protein degradation with small molecules, which have the potential to create novel therapeutic strategies. Using this approach, we can hopefully unlock the “undruggable” proteome and create a better strategy to combat diseases where therapeutic options are limited by conventional drug discovery approaches. One such targeted degradation tactic is with bifunctional molecules that recruit UPS components to degrade a target protein – more commonly referred to as PROTACs (PROteolysis-TArgeting Chimeras). While conventional small molecules must block the aberrant activity of a target protein, PROTACs serve to eliminate the protein altogether by routing it to the proteasome for degradation using the ubiquitin system. Since PROTACs deplete the targeted protein by degradation, much in the same way that functional genetics approaches (e.g. RNAi and CRISPR/Cas9) do, we will then be able to correlate molecular changes and predict cellular phenotypes much better – something which traditional therapeutics are usually unable to fully recapitulate. Furthermore, as traditional small molecules are always plagued with off-target effects, PROTACs can significantly improve on the predictability from gene-to-function studies by mimicking the effects seen in traditional genetic ablation studies.
Another aim is to develop biotechnologies for addressing important scientific questions requiring a cellular context, such as the monitoring of cellular protein-ligand interactions. This research is being led by my colleague, Nicholas Valerie.
Nicholas Valerie, post-doc
Johan Boström, PhD student
Maria João Pires, PhD student
Seher Alam, PhD student
Amarjit Saini, Assist. Prof. with Prof. Thomas Gustafsson Lab
Necessary cookies are absolutely essential for the website to function properly. This category only includes cookies that ensures basic functionalities and security features of the website. These cookies do not store any personal information.
Any cookies that may not be particularly necessary for the website to function and is used specifically to collect user personal data via analytics, ads, other embedded contents are termed as non-necessary cookies. It is mandatory to procure user consent prior to running these cookies on your website.