GBMSDG Meeting Archives
April 28, 2009
Paul R. West, Ph.D.
Director of BioAnalytical Chemistry
Stemina Biomarker Discovery
Predicting Human Developmental Toxicity Using Human Embryonic Stem Cells and Metabolomics
AstraZeneca Boston R&D
Special thanks to Agilent for sponsoring this event and AstraZeneca for hosting. It is the active participation of our sponsors that allows us to keep the fees for membership, dinners, drinks, speakers, etc. so low.
Costly, time-consuming animal models currently used to predict developmental toxicity of drugs do not adequately correlate to human response and are only about 60% accurate. We are addressing these issues by using an in vitro method that utilizes both human embryonic stem (hES) cells and LC-MS metabolomics to detect measurable modulation metabolites that will serve as biomarkers of developmental toxicity.
WA09 hES cells were dosed with 18 drugs of known teratogenicity. Both positive- and negative-ion HILIC-ESI-QTOF-MS data were acquired. "Mass Features" were then extracted from the raw LCMS data then filtered, binned and statistically analyzed. Data analysis was aided by the use of SteminaLIMS, a custom designed web-based laboratory management tool specifically designed to streamline the metabolomics based biomarker discovery workflow. Features of interest were identified (annotated) by searching the exact mass in public databases. Annotated mass features are being validated by comparing exact mass, chromatographic retention time and MS-MS product ion spectra to data from reference standards.
To date our research has resulted in the discovery of 34 significant features from the ESI(+) data and 14 significant features from the ESI(-) data. These mass features show significant fold changes directly correlated to drug teratogenicity.
About Paul West
Dr. West���s responsibilities at Stemina Biomarker Discovery include all mass spectrometric based metabolomic experimental design, LC/MS method development, data interpretation, processing and QC. Paul is an expert in small molecule mass spectrometry including LC/MS, MS/MS and HRMS with nearly 20 years of experience in mass spectrometry and the use of a variety of analytical techniques focusing on chemical structural identification for both known and unknown compounds. He also has thorough knowledge of cGLP/cGMP including qualitative analytical method development and validation.
Prior to working for Stemina, Dr. West worked for Abbott Laboratories in Illinois from 1994 until 2007 as an Associate Research investigator in the Structural Chemistry Department, where he implemented and coordinated analytical projects for the Global Pharmaceutical Research Division, focusing on LC/MS applications. Paul earned a BS in Chemistry from Cameron University in 1988 and a PhD in Analytical Chemistry (Mass Spectrometry) from Oklahoma State University in 1994.
Enjoying the company
Tom Trainor introduces Dr. West
Dr. West takes questions