Mass-spectrometry based clinical proteomics in biomarker research Webinar

Josip Blonder, MD

Head of the Clinical Proteomics Group, Laboratory of Proteomics & Analytical Technologies (LPAT), Cancer Research Technology Program, Leidos Biomedical Research, Inc. at NCIs, Frederick National Laboratory for Cancer Research (FNL)

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Thu October 17, 2013
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Biography

 

 

Dr. Blonder is Head of the Clinical Proteomics Group, Laboratory of Proteomics & Analytical Technologies (LPAT), Cancer Research Technology Program, Leidos Biomedical Research, Inc. at NCIs, Frederick National Laboratory for Cancer Research (FNL). In 1978, Dr. Blonder received his M.D. at the Rijeka University School of Medicine, Croatia. He completed a residency in emergency medicine in 1984 and assumed the position of head of Emergency Medicine, Medical Center Mostar. In 1989, he completed a fellowship in cardiology at the German Heart Institute in Berlin. 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). During the stay with Dr. Smith, his research focused on proteome-wide analysis of membrane proteins using high-accuracy and high-resolution mass spectrometry. In 2002 at the PNNL, he developed a shotgun proteomic method for profiling membrane proteins that resulted in an offer to join Leidos Biomedical Research, Inc. (formerly SAIC-Frederick Inc.), LPAT at NCI-Frederick. At the FNL, he extended the application of his method to global quantitative profiling of lipid raft and plasma membrane cell surface proteins resulting in significant discoveries subsequently confirmed in follow-up investigations using orthogonal molecular biology techniques [i.e., PLoS One. 2012;7(12):e51356; J Immunol. 2013 Jul 15;191(2):892-901.]. In 2006, Dr. Blonder was appointed as the head of Clinical Proteomics, extending his research to technology development that would allow in vivo molecular profiling of clinical tissue specimens and body fluids to facilitate a better understanding of cancer biology and cancer biomarker development. His group was the first to optimize the immunodepletion of tissue homogenates in the context of tissue directed proteomics for cancer biomarker discovery. This effort resulted in the publication [i.e., Anal Chem. 2010; 82(5):1584-8.] of a method that relies on concomitant analysis of tissue and blood specimens to unambiguously detect genuine tumor proteins in the blood of a patient diagnosed with non-metastatic cancer for biomarker discovery. Dr. Blonder brings a unique combination of his expertise in medicine, clinical proteomics, and bioinformatics to cancer research where he promotes the use of qualitative/quantitative shotgun proteomics and systems biology to better understand cancer biology. He leads active translational research focused on developing and applying advanced proteomics to directly profile cell surface proteins, solid tumors and body fluids in the context of molecular discovery/phenotyping using systems biology and pathway analysis. He is a lecturer at the Foundation for Advanced Education in the Sciences at NIH where he teaches a course on Clinical Proteomics and Biomarker Discovery. Since 2002, Dr. Blonder has authored over 50 scientific publications in areas of advanced mass spectrometry and clinical proteomics. He is an associate editor of BMC Cancer and a member of the American Association for Cancer Research and the American Society for Mass Spectrometry.

 

 

Abstract

 

Mass spectrometry (MS)-based profiling of clinical specimens has been increasingly used in biomarker 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. However, the discovery of valid cancer biomarkers 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 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 research/discovery.

   
   
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