MSACL 2017 US Abstract

Translational Mass Spectrometry

Amanda Paulovich (Presenter)
Fred Hutchinson Cancer Research Center

Bio: Amanda Paulovich, M.D., Ph.D. is a Member in the Clinical Research Division of Fred Hutchinson Cancer Research Center, and Professor in Medical Oncology at the University Of Washington School Of Medicine. Dr. Paulovich received her M.D. and Ph.D. (Genetics) at the University of Washington. She completed residency in Internal Medicine at Massachusetts General Hospital and a fellowship in Oncology at Dana-Farber. Her postdoctoral training was at MIT. Since 2003, her translational proteomic laboratory has been a major developer of multiple reaction monitoring mass spectrometry-based proteomic assays. She was inducted to American Society for Clinical Investigation, received the 2014 Life Science Innovation Northwest Women to Watch in Life Science Award, and received the 2015 Distinguished Achievement in Proteomic Sciences Award from the Human Proteome Organization.

Authorship: Amanda Paulovich
Fred Hutchinson Cancer Research Center, Seattle, WA

Short Abstract Proteins carry out the biological functions of our cells and form the basis of diagnostic tests and treatments, yet over 95% of human proteins can’t be studied because we lack reliable laboratory assays for quantifying their abundances. This lack of standardized assays for quantifying the majority of human proteins has left the proteome clinically inaccessible, contributed to poor inter-laboratory reproducibility of preclinical research, and is the biggest impediment to translating novel protein diagnostics into clinical use. Selected/multiple reaction monitoring mass spectrometry (S/MRM), especially coupled to the enrichment of target analytes, promises to relieve this limitation by offering a robust platform that enables efficient generation of highly sensitive, multiplex-able assays that are standardized to support high reproducibility across laboratories and platforms.

Long Abstract

The use of diagnostic biomarkers is essential for the realization of precision medicine and in translational research. Yet, currently there exist biomarker diagnostic assays for less than 600 proteins (LDT and FDA-cleared), a fraction (1-2%) of the total number of proteins encoded by the human genome. Mass spectrometry-based assays (Multiple Reaction Monitoring, also referred to as Selected Reaction Monitoring) have emerged as a viable platform for biomarker assays in modern disease management. I will present case studies of this methodology applied to different types of biospecimens for applications ranging from biomarker measurements to pharmacodynamic studies. I will also discuss ongoing efforts by the Clinical Proteomic Tumor Analysis Consortium (CPTAC) of the National Cancer Institute to set standards for MRM-based assay qualification and to make highly characterized assays (assays.cancer.gov) and monoclonal antibodies (antibodies.cancer.gov) available to the community.

Learning Objectives

1. Understand that the majority of the human proteome is clinically inaccessible, due to our reliance on antiquated technologies and a lack of standardized assays for measuring human proteins.

2. Understand that the lack of robust assays for quantifying proteins contributes to the irreproducibility of preclinical research, renders exciting experimental findings not actionable, and creates tremendous financial burden on the biomedical research enterprise.

3. Understand the current state-of-the-art for using MRM to quantify proteins, and become familiar with ongoing efforts to create a community assay resource to standardize protein assays and harmonize proteomic results.

References & Acknowledgements:

Financial Disclosure

IP Royalty: yes

IP Desc:licensing of monoclonal antibodies

Planning to mention or discuss specific products or technology of the company(ies) listed above:

yes