Protease Systems Biology

Our lab investigates how proteases shape biological systems in health and disease. We study protease networks and their substrates with a focus on impaired wound healing and inflammatory skin diseases, aiming to understand how dysregulated proteolysis impacts tissue repair and inflammation. Using mass spectrometry–based degradomics, we map protease activity across tissues, cell types, and disease states, and develop experimental and computational tools for substrate discovery, activity profiling, and specificity prediction.

We combine large-scale proteomics with data science and artificial intelligence to explore the dark proteome. Our group develops machine learning models for de novo peptide sequencing and applies them to proteoform analysis, metaproteomics, and post-translational modifications. Our efforts in this area enable exploration of regions of the proteome that are traditionally inaccessible to proteomics approaches.

Beyond characterization, we are interested in engineering and reprogramming proteases and their inhibitors to modulate biological pathways. We design and apply cutting edge protein design strategies for protease activity control, substrate selectivity, and the creation of synthetic proteolytic circuits for use in biotechnology and biomedicine. We also explore natural and engineered protease defense systems as emerging tools for targeted protein degradation and controlled signaling modulation.

Ultimately, our goal is to map, understand, and reprogram proteolytic systems across biology and disease. By integrating experimental proteomics, machine learning, and protein engineering, we aim to establish protease-based strategies for diagnostics, therapeutic development, and the emerging field of proteome editing.