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Jeffrey Sutherland, Ph.D.: A network based approach to understanding drug toxicity and its application to human liver disease

Friday, March 31 at 12:30 p.m. in IT 252

Abstract

Despite investment in toxicogenomics, nonclinical safety studies are still used to predict clinical liabilities for new drug candidates.  Network-based approaches help overcome challenges with whole-genome transcriptional profiling using limited numbers of treatments for phenotypes of interest.  In this presentation, I will describe the development and application of co-expression network analysis for safety assessment using rat liver gene expression results, organized in a visual representation of the transcriptome (the “TXG-MAP”).    Network responses compliment traditional histology-based assessment in predicting outcomes for longer studies and identify a novel mechanism of hepatotoxicity involving endoplasmic reticulum (ER) stress and Nrf2 activation.    Module-based molecular subtypes of cholestatic injury derived using rat translate to human.  Moreover, compared to gene-level analysis alone, combining module and gene-level analysis performed in sequence identifies significantly more phenotype-gene associations, including established and novel biomarkers of liver injury.

About Jeffrey Sutherland

Jeff Sutherland, PhD has experience in informatics, statistics and machine learning, data management, and software design.  Dr. Sutherland has a proven track record at the interface of chemistry, biology and information technology, where he has approached challenges ranging from analysis of high throughput screen data to clinical drug-drug interactions.  His research work in academia and industry has resulted in over 20 peer-reviewed publications in domains including computational chemistry, cheminformatics, cellular imaging, phenotypic screens, toxicology, systems biology and adverse drug reactions.

Dr. Sutherland is Vice President of Analytics at Sano Informed Prescribing, a startup developing diagnostics tests for the optimization of drug therapy.  Prior to arriving at Sano, Dr. Sutherland was Research Advisor in Tailored Therapeutics at Eli Lilly and Company.  He has held positions in research IT at Lilly, managing scientists working in all areas of drug discovery and development.  Dr. Sutherland received his undergraduate degree in Chemistry from Laurentian University, his doctorate in Chemistry at Queen’s University and post-doctoral research in at Eli Lilly.