Active Projects
1) Generate Targeted Protein Degradation Tools
What possibilities emerge when we harness protein degradation to rewire mitochondria and bacteria?
Our lab focuses on how novel chaperone and degron systems can be exploited to achieve targeted protein degradation in complex cellular compartments. Building on our previous work identifying new proteasome-based platforms, we are now extending these insights to design degradation tools for both mitochondria and bacteria.
We are particularly interested in uncovering the signals that guide recognition and degradation by conserved proteases such as ClpP and LonP across species. Understanding these rules will enable the creation of next-generation therapeutic strategies, spanning neurodegeneration, antibacterial development, metabolic disorders, and cancer.
2) Mapping Substrate Landscape and Activity Dynamics
How do differences in substrates and activity enable targeted treatments across species?
Many cancer cells abandon mitochondrial energy production in favor of glycolysis, even when oxygen is abundant, a metabolic shift that supports rapid growth. In contrast, healthy cells can flexibly switch between energy sources depending on environmental demands. The mitochondrial protease ClpP regulates key steps in energy production and is frequently overexpressed in cancer. We propose that ClpP plays a pivotal, yet underappreciated, role in driving metabolic reprogramming across different cell types. Understanding how ClpP shapes mitochondrial function could reveal novel vulnerabilities in cancer metabolism and inform new therapeutic strategies.
3) Peptidomemetric Library Generation
Can One-Bead-One-Compound Libraries Unlock New Protease Ligands?
In our lab, we create diverse libraries of peptidomimetic compounds to discover molecules that can selectively engage and modulate proteases like ClpX. By combining natural and specially designed non-natural building blocks, we generate thousands of unique compounds that can be rapidly screened and sequenced. Promising molecules are then tested in cells and in vitro using a variety of techniques to confirm their ability to bind and modulate their targets.
These chemical tools allow us to probe how ClpX functions in different cellular contexts, from mitochondria to bacteria, providing new insights into its roles in protein regulation, metabolism, and potential therapeutic applications.