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个人简介

Awards ASMS Biemann Medal, 2017 NSF CAREER Award, 2008 ASMS Research Award, 2006 Herbert Newby McCoy Award in Chemistry, 2003

研究领域

Research Interests Our lab focuses on the development of novel applications of mass spectrometry to investigate the chemistry and biology of proteins and related biomolecules. We have projects in diverse areas ranging from protein aging, to structural biology, environmental toxicology, isomer identification, or even more fundamental interests such as radical reactions or the physics of energy transfer. We use state-of-the-art mass spectrometers, lasers, and computational tools in our investigations, and we collaborate with other groups worldwide to expand our knowledge and access unique instrumentation. Biological Aging of Proteins Recent studies have demonstrated that long-lived proteins are far more abundant and relevant to disease than previously thought. For instance, roughly 30% of protein in the human body is long-lived. As proteins age, spontaneous degradation occurs, leading to structural changes and malfunction. Isomerization of specific amino acid residues is one of the most subtle and problematic changes that occurs due to aging because it is virtually impossible to detect. We have recently developed a radical chemistry, mass spectrometry-based method for identifying isomerization in long-lived proteins. Importantly, this has led to identification of sequences that greatly enhance susceptibility to isomerization, and these sequences are found in long-lived proteins associated with many diseases of aging, including cataracts, Alzheimer’s, and Parkinson’s. Understanding where and how these proteins age will help us understand how they contribute to these maladies, and suggest potential directions for treatment. Structural Biology Protein structure is the key to biological function or malfunction, which can lead to disease. Despite the desperate need, robust methods for rapid determination of protein structures are lacking. Recent advances in proteomics have led to the development of mass spectrometers with unrivaled sensitivity and speed, highly tuned for the analysis of peptides and proteins. The utility of these instruments for sequence analysis is unquestioned, but we are further developing the ability to examine three-dimensional structure via mass spectrometry. In this fashion, the speed and sensitivity of these instruments can be applied to the crucial function of protein structure determination.

近期论文

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Bonner, J.; Talbert, L. E.; Akkawi, N.; Julian, R. R. “Simplified Identification of Disulfide, Trisulfide, and Thioether Pairs with 213 nm UVPD” Analyst 2018, 143, 5176-5184. Riggs, D. L.; Hofmann, J.; Hahm, H. S.; Seeberger, P. H.; Pagel, K.; Julian, R. R. “Glycan Isomer Identification Using Ultraviolet Photodissociation Initiated Radical Chemistry” Anal. Chem. 2018, 90 (19), 11581-11588. Lyon, Y. A.; Sabbah, G. M.; Julian, R. R. “Differences in α-Crystallin isomerization reveal the activity of protein isoaspartyl methyltransferase (PIMT) in the nucleus and cortex of human lenses” Exp. Eye Res. 2018, 171, 131-141. Talbert, L. E.; Julian, R. R. Directed-Backbone Dissociation Following Bond-Specific Carbon-Sulfur UVPD at 213 Nm. J. Am. Soc. Mass Spectrom. 2018, 29 (9), 1760-1767. Lyon, Y. A.; Riggs, D.; Fornelli, L.; Compton, P. D.; Julian, R. R. “The Ups and Downs of Repeated Cleavage and Internal Fragment Production in Top-Down Proteomics” J. Am. Soc. Mass Spectrom. 2018, 29 (1), 150-157. Riggs, D. L.; Gomez, S. V.; Julian, R. R. “Sequence and Solution Effects on the Prevalence of D -Isomers Produced by Deamidation” ACS Chem. Biol. 2017, 12 (11), 2875-2882. Bonner, J.; Lyon, Y.; Nellessen, C.; Julian, R. R. “Photo-Electron Transfer Dissociation (PETD) Reveals Surprising Favorability of Zwitterionic States in Large Gaseous Peptides and Proteins” J. Am. Chem. Soc. 2017, 139, 10286-10293. Julian, R. R. “The Mechanism behind Top-Down UVPD Experiments: Making Sense of Apparent Contradictions” J. Am. Soc. Mass Spectrom. 2017, 28, 1823-1826. Lyon, Y. A.; Sabbah, G. M.; Julian, R. R. “Identification of Sequence Similarities among Isomerization Hotspots in Crystallin Proteins” J. Proteome Res. 2017, 16, 1797-1805. Lyon, Y. A.; Beran, G.; Julian, R. R. “Leveraging Electron Transfer Dissociation for Site Selective Radical Generation: Applications for Peptide Epimer Analysis.” J. Am. Soc. Mass Spectrom. 2017, 28, 1365-1373.

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