MSACL 2019 US Abstract

TDP-43 Enrichment using a High Affinity RNA Aptamer

Taylor Pobran (1), Junyan Shi (1), Mari L. DeMarco (1, 2)
(1) Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada (2) Department of Pathology and Laboratory Medicine, St. Paul’s Hospital, Providence Health Care, Vancouver, Canada

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Taylor Pobran (Presenter) University of British Columbia

Presenter Bio: I am currently a graduate student in Dr. Mari DeMarco’s lab at the University of British Columbia. Prior to my graduate studies, I received a Bachelor of Science in biochemistry from the University of Victoria. During my undergraduate degree, I had the opportunity to learn about mass spectrometry through co-operative job placements. After graduation, my growing interest in mass spectrometry lead me to join Dr. DeMarco’s laboratory to learn and acquire training in clinical mass spectrometry. My current research focuses on assay development for the enrichment and detection of a biomarker for frontotemporal dementia and amyotrophic lateral sclerosis.

Relevant Financial Disclosures (within past 24 months) No relevant financial relationship(s) to disclose. Discussing Products? NO, presenter will NOT present educational content related to products/services of the ineligible company(ies) listed above. Conflict mitigation NOT REQUIRED.

Transactive response DNA binding protein 43 kDa (TDP-43) has been identified as the major pathological protein in the majority of frontotemporal degeneration and amyotrophic lateral sclerosis cases. As such, there is great interest in detecting, characterizing and quantifying TDP-43 and its disease-related post-translational modifications to investigate pathogenesis. Detailed analysis of TDP-43 in matrices such as blood, brain tissue homogenate, and cerebrospinal fluid is hindered by the complexity of the matrix and/or the relatively low abundance of TDP-43. While immunoenrichment for molecules of interest is a strategy commonly used for improving detection, there are drawbacks to using antibodies in the assay workflow. Therefore, we developed an antibody-free enrichment workflow using RNA aptamers, followed by TDP-43 detection using liquid chromatography tandem mass spectrometry.