Activity-based Protein Profiling Approaches for Transplantation

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dc.contributor.authorNavarrete, Mario
dc.contributor.authorWilkins, John
dc.contributor.authorLao, Ying
dc.contributor.authorRush, David
dc.contributor.authorNickerson, Peter
dc.contributor.authorHo, Julie
dc.date.accessioned2020-09-11T21:48:08Z
dc.date.available2020-09-11T21:48:08Z
dc.date.issued2019-09
dc.date.submitted2020-09-11T17:47:36Zen_US
dc.description.abstractEnzyme activity may be more pathophysiologically relevant than enzyme quantity and is regulated by changes in conformational status that are undetectable by traditional proteomic approaches. Further, enzyme activity may provide insights into rapid physiological responses to inflammation/injury that are not dependent on de novo protein transcription. Activity-based protein profiling is a chemical proteomic approach designed to characterize and identify active enzymes within complex biological samples. Activity probes have been developed to interrogate multiple enzyme families with broad applicability; including but not limited to serine hydrolases, cysteine proteases, matrix metalloproteases, nitrilases, caspases and histone deacetylases. The goal of this overview is to describe the overall rationale, approach, methods, challenges and potential applications of activity-based protein profiling to transplantation research. To do so, we present a case example of urine serine hydrolase activity-based protein profiling in kidney transplant rejection to illustrate the utility and workflow of this analytical approach. Ultimately, developing novel transplant therapeutics is critically dependent on understanding the pathophysiological processes that result in loss of transplant function. Activity-based protein profiling offers a new dimension for characterizing dynamic changes in clinical samples. The capacity to identify and measure relevant enzyme activities provides fresh opportunities for understanding these processes and may help identify markers of disease activity for the development of novel diagnostics and real-time monitoring of patients. Finally, these insights into enzyme activity may also help to identify new transplant therapeutics, such as enzyme-specific inhibitors.en_US
dc.description.sponsorshipCanadian Institutes of Health Research (287559). Canadian Donation and Transplantation Research Program. Canadian Institutes of Health Research New Investigator Salary Award (340137). Flynn Family Chair in Renal Transplantation.en_US
dc.identifier.citationTransplantation 103(9): 1790-1798, 2019en_US
dc.identifier.doi10.1097/TP.0000000000002752
dc.identifier.issn0041-1337/19/10309-1790
dc.identifier.urihttp://hdl.handle.net/1993/35051
dc.language.isoengen_US
dc.publisherWolters Kluwer Healthen_US
dc.rightsopen accessen_US
dc.subjectserine hydrolaseen_US
dc.subjectserine proteaseen_US
dc.subjectproteinase-3en_US
dc.subjectproteomicsen_US
dc.subjectsubclinical rejectionen_US
dc.titleActivity-based Protein Profiling Approaches for Transplantationen_US
dc.typeresearch articleen_US
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