OCT 30, 2014 03:00 PM PDT
Clinical Shotgun Proteomics in Cancer Biomarker and Drug Target Research/Discovery
Presented at the Cancer: Research, Discovery and Therapeutics Virtual Event
30 46 2071

  • Group Leader - Clinical Proteomics, Cancer Research Technology Program (CRTP), Frederick National Laboratory for Cancer Research (FNL), Leidos Biomedical Research, Inc.
      Dr. Blonder leads the Clinical Proteomics Group at the CRTP/FNL. FNL is a Federally Funded Research and Development Center operated by Leidos Biomedical Research, Inc., for the National Cancer Institute (NCI).  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). At the PNNL, his research was focused on studying cell surface proteins using mass spectrometry (MS)-based proteomics. In 2002, Dr. Blonder joined FNL (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 on development of shotgun proteomics for in-depth profiling of membrane proteins found at the cell surface of cancer cells. In parallel, he worked on methodology for cancer biomarker and drug target discovery using precision proteomics for targeted profiling of clinical tissue and blood specimens. His group was the first to optimize the immunodepletion of abundant proteins from clinical tissue homogenates. Currently, Dr. Blonder is leading the effort towards molecular mapping of the KRAS cell surface as a part the RAS program. This program is spearheaded by the FNL as a national mission to attack RAS-driven cancers. Dr. Blonder brings unique combination of his expertise in medicine, clinical proteomics, and pathway analysis, focusing his research on the development of innovative approaches for molecular profiling of cancer cell lines, body fluids and tissue specimens. He is an editor of BMC Cancer and a lecturer at the Foundation for Advanced Education in the Sciences at NIH. Since 2002, Dr. Blonder has authored over 50 scientific publications in areas of biological mass spectrometry, clinical proteomics and cancer research. 

    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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