Mar 8, 2016 – MSDG Meeting

I. Dr. Sergei Dikler

Technical Project Manager,
Bruker Daltonics Inc., Billerica, MA

“MALDI High-Throughput Screening beyond 100,000 Samples per Day in Drug Discovery”

II. Dr. Reid Groseclose

Senior Investigator – DMPK, US (R&D Platform Technology & Science),
GSK, King of Prussia, PA

“Imaging Mass Spectrometry: Visualizing Biology and Chemistry in Drug Development”

Abstract for Talk I:

A novel automation system for high throughput screening in Drug Discovery has been developed with label-free molecular detection via high speed MALDI TOF MS analysis. The scalable solution features comprehensive robotic automation with sample preparation from assay plates, automated sample / matrix deposition and automated high density target plate processing with MALDI MS detection for unattended screening of thousands of samples per day. Assay development time is rapid, consumable and solvent usage / cost is minimized, and sample “readoutd” is 10x faster than other Mass Spectrometry workflows.

Abstract for Talk II:

Understanding the tissue distribution of a drug and its metabolites is an essential element in the development of safe and efficacious drugs. Imaging mass spectrometry (IMS) can determine the spatial distribution of an unlabeled drug and its metabolites in a tissue section with high sensitivity and specificity. Detailed molecular images of both exogenous and endogenous analytes can be correlated with the underlying tissue histology to produce very high information content datasets. This integrated imaging modality offers the potential to enhance our mechanistic understanding of disease progression and pharmacology (including toxicology) by providing snap shots of temporal and causal changes. Equally important, this new tool can serve as a common platform for engaging pathologist, clinicians, biologists and chemists in addressing a wide range of biological and chemical challenges.

This presentation will focus on our efforts to couple IMS and histology in drug development to gain mechanistic insights into drug correlated toxicities and efficacy. Case studies from early and late stage drug development where IMS was employed to investigate the mechanisms of adverse events, establish PK/PD relationships, and guide risk assessment will be presented.

Bio for Dr Dikler :

Sergei Dikler received his Ph.D. degree in Chemistry from the Texas A&M University under direction of Professor David H. Russell. Dr. Dikler joined Bruker Daltonics and has been working in the Applications Group specializing in MALDI-TOF/TOF applications. He led or participated in the new product development projects such as the development of MALDI PharmaPulse system and the development of NALDI targets. Dr. Dikler worked on new method development for MALDI-TOF and MALDI-TOF/TOF instruments including high-throughput screening, de novo sequencing of neuropeptides, clinical proteomics, LC-MALDI, species identification based on intact protein profiling, top-down and middle-down sequencing of intact proteins and many other projects that resulted in numerous conference presentations and papers in peer reviewed journals. In 2009 his work was featured in Genetic Engineering & Biotechnology News magazine.

Bio for Dr Groseclose:

Reid Groseclose is a Senior Investigator in the Bioimaging group at GlaxoSmithKline located in Upper Merion, Pennsylvania. Reid received his B.S. in chemistry from the University of Tennessee in 2004 and his Ph.D. in chemistry from Vanderbilt University in 2009 in the lab of Richard Caprioli, where his work focused on exploring the utility of MALDI imaging mass spectrometry and proteomics for the analysis and classification of cancerous tissues. He joined GlaxoSmithKline in 2009, where his research interests have centered on the application of MALDI IMS to determine the tissue distribution of drugs and their metabolites and investigating the mechanisms of disease pathogenesis, pharmacology and toxicology.