About FDA

Systems Biology

Director:  William B. Mattes, Ph.D., DABT

The Division of Systems Biology focuses on the development and evaluation of new technologies and the identification of new biomarkers (disease indicators) to support the FDA mission.

The Division is divided into three branches:

  • Biomarkers and Alternative Models Branch—Finds new translational biomarkers—biomarkers that can be researched in animals and then applied to humans—to a) improve detection of unsafe drugs and other FDA-regulated products and b) improve the identification of disease onset and its progression to enable faster and more effective medical intervention. Also investigates usefulness of cell-culture models to examine various types of toxicity; such models can reduce or replace animals in testing of FDA-regulated products for safety.
  • Innovative Safety and Technologies Branch—Develops and evaluates innovative methods to detect unsafe products, advance the identification of infectious disease, and enhance disease-detection procedures.
  • Personalized Medicine Branch—Determines the differences in responses to drugs among specific groups of humans, with an eye to how these differences are seen in specific groups of other species. These differing responses are compared using current assessments of drug safety and effectiveness.
Scientist conducting systems biology-related research

As the diagnosis and treatment of disease advances, so must the science that regulates and supports such advances. The Division of Systems Biology is focused on using cutting-edge approaches to contribute to the advancement of regulatory and support science. Systems biology uses experimental data and computational analysis to map out body responses to drugs and disease, and compare these responses between animals and humans. An integrated systems-biology strategy using “omics" technologies is being applied to questions related to the safe and effective use of FDA-approved drugs and devices and the hazards of tobacco products. Innovative cell-based (in vitro) and computer-based (in silico) methods are developed and evaluated for their ability to expand the FDA’s regulatory science toolkit, as well as their value in supporting medical science.


Recent Division Accomplishments
  • Examining animal models we found a dramatic increase in HMOX1 levels in plasma from rats overdosed with acetaminophen (also known as APAP) that was correlated with liver damage. This study provided insights into the mechanisms of APAP-induced liver toxicity and identified a unique protein, HMOX1, as a potential plasma biomarker of liver injury.
  • Certain microRNA (miRNA) species might be biomarkers of liver damage, as we found increased levels in the body fluids of rats exposed to drugs that cause liver damage, but not those exposed to control compounds.
  • A mouse model of drug-induced cardiac injury was developed to study the cardiotoxicity of the potent anti-cancer drug known as doxorubicin. As a result, biomarkers of early cardiotoxicity were discovered.
  • RAPID-B™ is a technology that was developed by researchers within this division and has been licensed to a commercial entity. This is a flow-cytometric-based approach using a field-tested machine. A successful internal FDA level-3 validation of the E. coli O157 (a variant of a bacterium that causes severe food poisoning) was performed in collaboration with the FDA’s Office of Regulatory Affairs’ Arkansas Regional Laboratory.
  • The Mouse Embryonic Stem Cell Test has been used to examine agents that induce developmental toxicity. The current assay uses differentiation to cardiomyocytes as an endpoint; we have examined the use of differentiation to osteoblasts as a parallel endpoint. Our results suggest that differentiation to osteoblasts may provide confirmatory information in predicting embryotoxicity.

Ongoing Systems Biology Research Topics

Liver Toxicity

  • Researching methods that can detect disease in easily obtained body fluids, such as blood and urine to identify translational biomarkers (i.e. tests that work in both animals and humans) of drug-induced liver injury.
  • Identifying new human biomarkers that will determine the underlying causes associated with adverse responses to FDA-regulated products, specifically those containing acetaminophen.

Heart Toxicity

  • Establishment of animal and human cell models of drug-induced heart injury, in particular those that can lead to congestive heart failure.
  • Development of predictive biomarkers for heart injury associated with doxorubicin, an otherwise effective cancer drug, using a systems biology approach.

Pharmacogenetics and Pharmacogenomics (using individual’s genetic profile and how it relates to drug response)

  • Whole-genome sequencing—analyzing an individual’s complete genetic profile—to identify genetic causes of adverse reactions to carbamazepine. This chemical/drug is commonly used to treat seizures and nerve pain, as well as bipolar disorder.
  • Investigation of genetic susceptibility to clopidogrel—a drug used to prevent clotting of the blood in patients with various artery and vein diseases—and aspirin adverse events.

Food and Biological Product Safety

  • Rapid screening of food or drugs for chemical or microbiological contamination.
  • Rapid and sensitive detection of the agents that cause Creutzfeldt-Jakob disease (human “Mad Cow Disease”)—a form of brain damage—in tissue and blood donations.

In Silico Approaches to Model Toxicity

  • 3D- and 4D-QSDAR (Quantitative Structure-Activity Relationship) modeling applied to various toxicological endpoints. This approach simulates how a chemical might cause a toxic effect by looking at the information found in atom-to-atom interactions in chemicals. This project will specifically attempt to meet FDA’s need for computational tools to accurately predict which compounds in food, drugs, or the environment could be harmful.
  • Understanding and predicting the body’s response to drug reactions using a molecular-modeling approach. This study is consistent with FDA's pledge to develop new scientific approaches to detecting, understanding, predicting, and preventing adverse events.
  • Establishment of mouse-embryonic stem cells as an in vitro cell-culture model to predict compounds that might cause birth defects.
  • Use multiple high-throughput assays to investigate the effects of fructose on human fat cells compared to the effects of glucose.


The NCTR Annual Report contains information on the latest accomplishments and plans for the Division of Systems Biology as well as project and publication listings.







Contact FDA

National Center for Toxicological Research

Food and Drug Administration

3900 NCTR Road

Jefferson, AR 72079

Page Last Updated: 08/07/2018
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