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September 20, 2011

CAAT Receives $6 Million NIH Director's Grant to Pioneer Transformative Research in Toxicology Testing

The Johns Hopkins Center for Alternatives to Animal Testing (CAAT) has received a $6 million grant from the National Institutes of Health (NIH) to pioneer potentially revolutionary new methods for toxicological testing to improve human health and reduce animal testing.

CAAT Director Thomas Hartung, MD, PhD, and his team at the Johns Hopkins Bloomberg School of Public Health, along with partner Agilent Technologies and noted scientists from government and industry, received the funding for a consortium to develop a new technological methodology for mapping the molecular pathways of toxicity within cells. Funding for the project comes from the Common Funds NIH Director's Transformative Research Projects Program (R01), which is designed to support exceptionally innovative, high risk, original and/or unconventional research that has the potential to create or overturn fundamental scientific paradigms.

Current toxicological testing relies on a patchwork of 40+-year-old animal tests that are expensive (more than $3 billion per year), time-consuming, and often provide results of limited predictive value for human health. The low-throughput of current toxicity testing approaches (which are largely the same for industrial chemicals, pesticides, and drugs) has led to a backlog of more than 80,000 chemicals for which potential toxicity remains largely unknown.

Scientific understanding of how genes, proteins, and small molecules interact to form molecular pathways that maintain cell function has evolved rapidly, thanks to advances in molecular and computational tools. Pathways that lead to adverse health effects when perturbed are referred to as pathways of toxicity (PoT).  "Mapping the entirety of these pathways which have termed the Human Toxome will be a large-scale effort, perhaps on the order of the Human Genome Project," Hartung said.

As a first step to mapping the Human Toxome, Hartung and his collaborators have proposed comprehensively mapping the pathways of endocrine disruption, a perturbation of the hormonal system that can cause tumors, birth defects, and developmental disorders. The physiological pathways of the endocrine system are relatively well understood, making PoT identification simpler than for other potential targets. The team will develop a common, community-accessible framework that will enable the toxicology community at large to comprehensively and cooperatively map the human toxome using integrated testing strategies that combine omics (transcriptomics and metabolomics) data with computational models. The consortium will also create a public database of PoT, enabling full access to researchers around the world.

Along with Hartung, the other principal investigators include James Yager, Bloomberg School of Public Health; Robert Kavlock, Director of the National Center for Computational Toxicology at the U.S. Environmental Protection Agency (EPA); Michael Rosenberg, Director of Genomics Software Life Science Group at leading systems biology technology provider Agilent Technologies; Mel Andersen, Associate Director of the Hamner Institute for Health Sciences; Kim Boekelheide, Professor of Medical Sciences at Brown University; and Albert J. Fornace, Jr., Molecular Cancer Research Chair at Lombardi Comprehensive Cancer Center, Georgetown University Medical Center.

More information on the Transformative Research Projects Award is at including information on this year's awardees.

Thomas Hartung's paper, Food for Thought: On Mapping the Human Toxome, can be found at:

Media contact: Tim Parsons, director of Public Affairs, at 410-955-7619 or