Our laboratory is interested in developing a complete understanding of the physiological functions of the ubiquitin and sixteen other ubiquitin-like systems in living organisms, and in translating the obtained knowledge into clinical applications. We use chemistry as a tool to discover new components of the ubiquitin and ubiquitin-like systems, and to perturb every component of the ubiquitin and ubiquitin-like systems rapidly and reversibly with small molecule inhibitors or activators, thus connecting the observed phenotype with the protein function. Our specific research interests include the design of selective inhibitors or activators of the ubiquitin and ubiquitin-like protein conjugation and deconjugation pathways with the overarching goal to build a mechanistic model of how ubiquitin and sixteen other ubiquitin-like proteins regulate eukaryotic cell cycle on both transcriptional and translational levels. In addition, we use chemical approaches to dissect the role of the ubiquitin and sixteen other ubiquitin like systems in signal transduction, and mitosis. Our methods are highly interdisciplinary and include X-ray crystallography and mass spectrometry techniques, computational methods, biochemistry, and systems pharmacology. Another area of interest includes the development of selective small molecule probes to understand the physiological functions of autophagy, and the development of methods to locate ubiquitin and ubiquitin-like protein epigenetic modifications on the chromatin, and the role of these chromatin modifications in human diseases such as cancer.