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Bryon Drown

Bryon Drown

The focus of our lab is to understand how post-translational modification of proteins affects their function, particularly in the context of drug-protein interactions. Variance in protein structure abounds and can have profound impact on function. While more widely practiced proteomics approaches focus on individual sites of modification, we seek to observe and characterize intact proteoforms. Proteoforms are entities that contain all the variability in chemical composition arising from sequence variation, alternative splicing, and post-translational modification. To measure proteoforms, we use top-down protein mass spectrometry which differentiates itself from the more widely practiced bottom-up mass spectrometry in that intact proteoforms are ionized rather than peptides. By keeping proteins intact, we can interrogate the interaction of multiple modification sites. Using this technique, we are pursuing three areas of research:

Proteoform-specific drug interactions

Precision medicine is a powerful approach for treating diseases that exploits disease-specific mutations to develop agents that specifically target diseased tissue without harming healthy cells. Although an impactful strategy, we are working to expand the approach by designing proteoform-specific drug interactions. By measuring these interactions with top-down mass spectrometry, we aim to better understand the pharmacodynamics of existing drugs and identify new drug targets.

Probe synthesis for PTM-focused top-down proteomics

Proteome-wide top-down mass spectrometry is an effective method for discovering proteoform biomarkers and monitoring drug response. The depth of coverage is limited by current separation techniques for intact proteins and decreased sensitivity for larger proteins. As a result, some post-translational modifications are underrepresented in most unbiased top-down proteomics datasets. We are using metabolically incorporated probes and affinity reagents to isolate specifically-modified proteoforms to better access these under-studied populations. In addition to using well-established probe molecules, we are also designing and synthesizing new probes to expand the repertoire modifications to study.

Targeted native mass spectrometry

Native protein mass spectrometry is a unique analytical technique that compliments other structural biology approaches. By ionizing intact protein complexes bound to small-molecule and metal ligands, native mass spectrometry can provide critical insight into the composition and stoichiometry of multi-protein assemblies. However, measuring lower-abundance endogenous complexes this way is difficult due to challenges with enriching them without disturbing their native form. By implementing specific bioconjugation techniques, we will create renewable affinity reagents that can isolate protein complexes and prepare them for native mass spectrometry.

Training Opportunities

Students working on the projects above have opportunities to receive training in organic synthesis, mammalian cell culture, protein conjugation chemistry, and protein mass spectrometry. We are currently seeking graduate students.


B.S., Wheaton College, 2012

Ph.D., University of Illinois at Urbana-Champaign, 2019

Post-doctoral Fellow, Northwestern University, 2022


List of publications