OCT 30, 2014 3:00 PM PDT

Clinical Shotgun Proteomics in Cancer Biomarker and Drug Target Research/Discovery

Speaker
  • Senior Scientist, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research (FNLCR)
    Biography
      Dr. Blonder is the Clinical Proteomics Lead at the Cancer Research Technology Program at Frederick National Laboratory for Cancer Research (FNLCR), operated by Leidos Biomedical Research, Inc. For the National Cancer Institute. In 1978, Dr. Blonder received his M.D. at the Rijeka University School of Medicine, Croatia. In 2000, through Associated Western Universities, Dr. Blonder was awarded a post-doc fellowship in proteomics at the Pacific Northwest National Laboratory (PNNL), Richland, WA (Advisor: Dr. Richard D. Smith). In 2002, Dr. Blonder joined the Laboratory of Proteomics & Analytical Technology, at the FNLCR (formerly NCI-Frederick) where he continues to develop and apply MS-based proteomics to cancer research. Since 2006, he has led the Clinical Proteomics Group, extending his research to in-depth profiling of membrane proteome. In parallel, he worked on the methodology for cancer biomarker and drug target discovery using clinical specimens. His group was the first to optimize the immunodepletion of abundant proteins from tissue homogenates. In 2013, Dr. Blonder joined the Antibody Characterization Laboratory to lead the cell surface project within the Ras Initiative at the FNLCR/NCI focused on discovery of cell surface targets, enriched or unique to cancers driven by mutated RAS that could be targeted by drugs, antibodies, antibody-drug conjugates, or nanoparticles. This effort resulted in the first cell surface proteome map of a model cell line expressing oncogenic KRasG12V. Dr. Blonder brings unique combination of his expertise in clinical proteomics, medicine and systems biology, focusing his research on the development of innovative approaches for cancer biomarker and drug target discovery. He is an editor of the BMC Cancer and a lecturer at the Foundation for Advanced Education in the Sciences at NIH. Dr. Blonder has authored over 60 scientific publications in areas of biological mass spectrometry, clinical proteomics and cancer research.

    Abstract

    Mass spectrometry (MS)-based profiling of clinical specimens has been increasingly used in cancer research to characterize changes in protein expression between tumor and healthy tissue or between the blood of diseased and healthy individuals. These molecular profiles may lead to distinct insights that are not readily evident using in vitro cultured cells or animal models and may facilitate discovery of clinically applicable biomarkers and novel drug targets. However, the discovery of valid cancer biomarkers and drug targets using MS-based proteomics has proven difficult, primarily due to the analytical challenges exemplified in the wide dynamic range of human plasma protein levels (i.e., > 10 orders of magnitude) and the fact that the 10 most abundant proteins constitute ~ 90% of the total plasma protein mass. Analytical challenges related to MS-based profiling of clinical samples obtained from diverse patient populations are complex, different from those in basic cancer research characterized by controlled experimental conditions employing in vitro cultured cells or transgenic animals. Therefore, experimental design and sample preparation represent the most challenging steps within a clinical proteomic workflow aimed at the development of reproducible and high-throughput methods for cancer biomarker and drug targets discovery. This presentation focuses on our recent advances in experimental design and method development using high resolution/accuracy MS-based proteomics for molecular profiling of clinical specimens in the context of cancer biomarker and novel drug targets research/discovery.


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