Coupling quantitative biological mass spectrometry with genetic manipulation to understand how proteins contribute to disease and the ef cacy of therapies
Using biological mass spectrometry and other proteomics-based methods, the James Lab investigates how proteins become dysregulated in inflammatory disease and lymphoma. These techniques can be used to evaluate changes in protein abundance and protein modifications (including phosphorylation, ubiquitylation, and acetylation), alterations in cell membrane and nuclear protein expression, changes in protein-protein interaction partners, etc. in disease states and upon pharmacological treatment or genetic manipulation. This quantitative data helps us understand which signaling pathways contribute to disease and which prevent effective responses to specific therapies.
Using this established framework for integrating genetic and quantitative proteomics data, James’ research is increasing our understanding of how pathogenic gene variants found to be associated with asthma, diabetes, lupus and other inflammatory disease impact the proteome of immune cells. By modeling how specific genetic variants alter global protein function in pathogenic cells and by determining how the protein-protein interaction networks of these proteins are altered in the variant setting, James hopes to develop targeted mass spectrometry-based assays that can be used clinically to predict which therapies may be effective in patients that express these variants.
In addition to his work in inflammatory diseases, James is also investigating why some patients with B cell lymphoma develop resistance to targeted therapies, specifically kinase inhibitors. The goals of this work are to:
James is interested in establishing industry collaborations in which his expertise in quantitative proteomics and targeted mass spectrometry can be utilized to understand and monitor aberrant cellular signaling in inflammatory diseases and lymphoma. The James Lab is also interested in leveraging their proprietary data sets to develop antibody and/or small molecule targeting reagents in an effort to target protein-based pathways that promote drug resistance or pathogenesis in inflammatory disease.
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biological mass spectrometry
protein-protein interaction partners
protein-protein interaction networks
specifically kinase inhibitors
inhibitors discover drugs
