UAMS Researcher Honored by Society of Toxicology

By Yavonda Chase

The award recognizes the best paper published during a 12-month period in the Society of Toxicology’s journal, Toxicological Sciences. Any member of the society can nominate one title for the honor, but no more than six papers are submitted for final consideration by the journal’s editor in chief.

The paper, published in August 2014, was titled “A Systems Biology Approach Utilizing a Mouse Diversity Panel Identifies Genetic Differences Influencing Isoniazid-Induced Microvesicular Steatosis.”

Harrill and others in her laboratory worked in close collaboration with scientists from Pfizer, which funded the study, as well as researchers from RTI International and Janssen Pharmaceuticals Inc.

“The goal of the study was to determine whether we could figure out why some individuals are susceptible to adverse drug events while other individuals can tolerate it well,” said Harrill. “We did this by using a genetically diverse mouse population and by measuring effects of isoniazid, a tuberculosis treatment known to cause liver injury, on the mice. By doing so, we can mimic the range of drug-related responses that occur in diverse patient populations.”

The team confirmed that certain strains of mice were more prone to isoniazid’s liver effects. They then used a systems biology approach – combining gene expression, small molecule analysis, and genetic sequence analysis to determine why some individuals are more sensitive to isoniazid’s effects.

The Society’s Board of Publications praised the team’s use of the genetically diverse mouse population and called the “work an excellent example of the use of systems biology within the field of toxicology.”

Harrill is a member of the U.S. Federal Drug Administration’s Pharmaceutical Science and Clinical Pharmacology Advisory Committee and is co-chairing the Application of Genomics to Risk Assessment committee through the International Life Sciences Institute’s Health and Environmental Sciences Institute.

She served as a senior author of the research with Karissa Adkins of Pfizer. Other authors were Rachel Church, Hong Wu, Merrie Mosedale, Susan Sumner, Wimal Pathmasiri, Catherine (Lisa) Kurtz, Mathew Pletcher, John (Scott) Eaddy, Karamjeet Pandher, Monica Singer, Ameesha Batheja and Paul Watkins.

The Society of Toxicology is a professional and scholarly organization of more than 7,800 scientists from academic institutions, government and industry around the world.

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