Our lab uses structural biological methods with state-of-the-art biophysical and biochemical techniques to elucidate the molecular mechanisms of action of ubiquitin ligases and ubiquitin-conjugating enzymes. These include x-ray crystallography, cryoEM, molecular modeling, pre-steady state kinetics by stopped-flow and quench-flow based approaches, and proteomics using mass spectrometry.
The cullin-RING ligases, also known as the CRLs, are by far the most abundant ubiquitin ligases in human cells. While they are of clear biological importance at both cellular and organismal levels, the CRLs have recently garnered great interest as therapeutic tools to treat major human diseases. The Kleiger lab is involved in both basic biological research questions as well as the emerging technology of targeted protein degradation. Our research group engages with industry leaders including Genentech and Amgen as well as cutting-edge academic collaborators such as the Schulman lab, located at the Max Planck Institute of Biochemistry, Munich, to name a few.