Our lab is dedicated to advancing mass spectrometry-based structural proteomics, with a particular focus on techniques including footprinting, crosslinking, and hydrogen-deuterium exchange (HDX). These methods enable us to probe the intricate details of protein structure, including interfaces, solvent accessibility, binding affinities, and the mechanisms behind protein folding and unfolding.

A major emphasis of our research is on membrane proteins, which are notoriously challenging to study due to their complex and dynamic environments. We are pioneering novel footprinting techniques tailored for these proteins, both in membrane mimics and, ultimately, within native cellular contexts. The insights gained from our work hold significant potential for drug discovery and a deeper understanding of disease mechanisms, including cancer and neurodegenerative diseases like Alzheimer’s.

One of the cornerstone techniques we employ is Fast Photochemical Oxidation of Proteins (FPOP). In this method, we generate hydroxyl radicals from hydrogen peroxide using a pulsed laser (248 nm), which selectively oxidizes surface-exposed amino acid residues. This “painting” of proteins allows us to map protein-protein interfaces, assess binding affinities, and contribute to drug discovery efforts, including epitope mapping. FPOP’s utility extends beyond academia; it is increasingly adopted by biotechnology companies for the quality control of protein therapeutics and for identifying interaction sites between therapeutic proteins and their targets.

1. Sun, J.H. Song, M.K. Danielson, N.D. Colley, A. Thomas, D. Hambly*, J.C. Barnes*, M.L. Gross*, Development of a high-throughput mass spectrometry-based Sars-Cov-2 immunoassay. Analytical Chemistry, 2023.
2. HC Yang, W Li, J Sun*, ML Gross*, Advances in mass spectrometry on membrane proteins. Membranes, 2023, 13 (5), 457.
3. Sun, W.K. Li, M. L. Gross, Advances in mass spectrometry-based footprinting of membrane proteins. Proteomics, 2022.
4. S Li, J Sun, S Liu, F Zhou, M Gross, W Li*, Missense VKOR mutants exhibit severe warfarin resistance but lack VKCFD via shifting to an aberrantly reduced state. Blood Advances, 2022, 2021006876.
5. Sun, X. R. Liu, S. Li, W.K. Li*, M. L. Gross*, Nanoparticle and photochemistry for native-like membrane protein footprinting. Nature Communications, 2021, 12, 1-10.
6. Sun, S. Li, W.K. Li, M. L. Gross*, Carbocation Footprinting of soluble protein and membrane protein. Analytical Chemistry, 2021.
7. M. Jiang, J Sun*, C.Q. Xiong*, H.H. Liu, Y.Z. Li, X Wang, Z.X. Nie*, Mass spectrometry imaging reveals in situ behaviors of multiple components in aerosol particles. Angewandte Chemie International Edition, 2021, 60, 23225. Hot paper and inside cover.
8. J. Xue, H.H. Liu, S.M. Chen*, C.Q. Xiong*, L.P. Zhan, J. Sun, and Z.X. Nie*, Mass spectrometry imaging of the in situ drug release from nanocarriers, Science Advances, 2018, 4, eaat9039.