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Mass Spectrometric Immunoassays of Human Plasma

presented by

Randall W. Nelson
Professor
Arizona State University

March 21, 2007

W.M. Keck Foundation Amphitheater - BCC1


Background:

     The focus of Dr. Nelson's career has been primarily on the development of mass spectrometric technologies and methods for the characterization of biomolecules residing in various biological milieu. In 1986, he received his BS in Chemistry from Eastern Oregon State College (LaGrande, OR), and in 1990 received his Ph.D. in Chemistry in Arizona State University (Tempe, AZ), where, under the mentorship of Prof. Peter Williams, his thesis topic was the development of laser desorption/ionization approaches from frozen aqueous media fro the mass spectrometry of DNA. From 1990 to 1993, Dr. Nelson occupied the roles of Senior Research Scientist and Product Manager at Vestec Corp. (Houston, TX, subsequently brought by Applied Biosystems, Inc.), where he oversaw the development of the worlds's first commercial line of MALDI-TOF mass spectrometers. From 1994 to 1997, he returned to the Department of Chemistry and Biochemistry at Arizona State University as an Academic Professional/Visiting Assistant Professor. During this time, he developed a number of proprietary methods and devices for the detailed analysis of proteins from biological fluids. These technologies include mass spectrometric immunoassay (MSIA), bioreactive mass spectrometer targets (BRP) and surface plasmon resonance mass spectrometry (SPR-MS). From 1997 to 2006, Dr. Nelson undertook the roles of President and CEO of Intrinsic Bioprobes, Inc. (Tempe, AZ), which he co-founded to commercialize these technologies. Currently, Dr. Nelson is Director of Molecular Biosignatures Analysis Unit within The Biodesign Institute at Arizona State University, where he also holds the position of Research Professor and Adjunct Professorship in the Department of Chemistry and Biochemistry. One of the objectives of the MBAU/BDI is to apply the novel proteomics and mass spectrometric technologies and methodologies to the study and understanding of diseases of the human populations. Dr. Nelson has published 100 peer-reviewed manuscripts regarding biological mass spectrometry and proteomics, and is inventor or co-inventor on 22 issued and 25 pending patents covering mass spectrometric technologies and methods.

Abstract:

     Critical to using MALDI-TOFMS based platforms for disease diagnostics is the need to transcend from the general profiling of proteins to the specific targeting of panels of proteins. The value of such targeted approaches lies in the ability to generate data on only the specific molecular determinants relevant to the disease. Thus, it is important to reduce significant findings from any clinical (proteomics) study to its essential components, try to understand the physiological relevance of such findings, design targeted multiplexed assays and analyze thousands of real-world samples - i.e., to meet some fundamental criteria for a diagnostics platform. Over the past decade, we have devoted much effort to meeting these objectives, in the form of Mass Spectrometric Immunoassay (MSIA).


     Data from the studies will be given to illustrate the high throughput application of MSIA in targeted plasma proteome analysis. In one example, MSIA was used to characterize a panel of 25 proteins from the (blood) plasma of 96 healthy individuals. In each instance, the targeted-protein was characterized for each individual as wild-type or non-wild-type, and if non-wild-type, the identity of the variant was determined. From these collective data, the frequency of occurence of each variant was established for the 96-individual cohort, as well as semi-quantitative data regarding relative abundance of the variants. In all 2,500 targeted analyses were performed, which resulted in the observance of > 75 protein variants within the 96-individual cohorts (as opposed to the observation of 25 wild-type proteins). Based on these initial findings, proteins in disease-state samples were screened using identical MSIA protocols to evaluate potential structural changes related to the disease(s). Findings will be presented from targeted MSIA analysis of cardiovascular disease and cancer samples, and how these findings are used to develop second and third generation multiplexed MSIA assays for use in disease detection.

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