WK Lab

The molecular basis for protein secretion in hypoxia. Many adverse effects of tumor hypoxia, such as increased migration, invasion, angiogenesis and immune suppression, are mediated by secreted proteins. Most secreted proteins contain disulfide bonds, but it is unknown how these can form in the absence of oxygen (Koritzinsky et al, 2013; Levitin et al, 2021). We aim to identify pathways for disulfide bond formation and secretion in hypoxia, with the ultimate goal to target these pathways to prevent aggressive tumor phenotypes.

The role of redox homeostasis in innate immunity. We have discovered a dependency for pancreatic cancer cells on the anti-oxidant protein peroxiredoxin 4 (PRDX4) (Jain et al, 2021). We are now investigating how loss of redox homeostasis in cancer cells can lead to innate immunity signaling, and whether this can be leveraged for therapeutic purposes. We also aim to develop small molecule inhibitors targeting PRDX4 activity.

Metabolic deregulation in cancer.  Recent work from our lab has identified 2-aminoethanethiol dioxygenase (ADO) expression as a vulnerability for liver cancer cells (Lee et al, 2024). Loss of ADO leads to deregulation of metabolism and gene expression, and severe oxidative stress. We now aim to decipher how ADO regulates gene expression, with a focus on regulation of mRNA translation and hypoxia adaptation.