Chemical Biology

Our laboratory has adopted ‘the small molecule approach’ to biology. We study cell biology at the molecular and atomic levels using an integrated approach combining synthetic organic chemistry and molecular biology techniques. We custom design our probes to interrogate cell processes relevant to human diseases. For example, we have established protocols based on click chemistry to fluorescently label small molecules in cells with the view to shed light on their mechanisms of action. This, combined with multi-omics has revealed previously uncharted molecular features in cells that promote the disease-state, while offering opportunities for small molecule intervention. For instance, we have discovered a novel mechanism of metal uptake involving the plasma membrane glycoprotein CD44 and its ligands hyaluronates. We have identified an iron-dependency of the mesenchymal state of cancer cells, which confer a vulnerability of this cell state to ferroptosis. More recently, we have uncovered a previously uncharted role of mitochondrial copper in the regulation of immune cell activation and epithelial-mesenchymal transition of cancer cells. We found that targeting these metals in the disease-state with in-house small molecules confers therapeutic benefits in vivo. Thus, our laboratory exploits universal principles of physical chemistry and knowledge of biology to impact human medicine.