The Rudd lab investigates metabolic pathways operating inside cancer cells and how these pathways support malignant disease. We are particularly focused upon the metabolic interplay between the DNA precursor pool and the DNA molecule, a relationship that is fundamental to cancer biology, underpinning key aspects of oncogenesis together with therapy resistance. We apply a multidisciplinary approach centred upon gaining a detailed mechanistic understanding of these pathways, allowing the identification of potential biomarkers and therapeutic targets that can be exploited to rationally improve the treatment of cancer.
The utility of this approach was underscored by our work on chemoresistance in acute myeloid leukaemia. Following identification of a key regulator of DNA precursor pools as a chemoresistance factor (Herold et al., 2017), we exploited elevated expression of this enzyme by uncovering a collateral sensitivity to a combination chemotherapy, identified through phenotypic screening (Rudd et al., 2020). In addition, we also established methodologies to identify small molecules capable of inactivating this enzyme (Yagüe-Capilla & Rudd, 2021).
sean.rudd@ki.se