About FDA

Systems Biology

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

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. An integrated systems biology strategy utilizing genomics, metabolomics, and proteomics technologies is being applied to questions related to the safe and effective use of FDA-approved drugs and devices, and the toxicity of tobacco products. Studies are conducted to identify important translational biomarkers and pathways of responses that provide predictive, diagnostic, and prognostic value in both the preclinical testing of compounds and the management of patients. Innovative in vitro cell culture and in silico models are developed and evaluated for their ability to expand the FDA"s regulatory science toolkit as well their value in supporting medical science. 

The following model systems are used to address critical issues including hepatotoxicity, cardiotoxicity, developmental toxicity, disease and toxicity/disease susceptibility:

  • pluripotent stem cells
  • primary and transformed cell lines
  • animal models
  • clinical samples
  • in silico models  

New innovative approaches are being developed to:

  • identify toxic agents that will cause adverse effects in humans,
  • detect and classify pathogenic bacteria and other infectious agents in food and biological products, and improve the diagnostic accuracy of medical imaging 


Biomarkers and Alternative Models Branch

Mission: 1) To discover and evaluate translational biomarkers of toxicity and disease using cutting edge systems biology approaches in preclinical and clinical studies, and 2) To develop alternative models (e.g., stem cells) to assess toxicity and efficacy of FDA-regulated products. These alternative assays could be higher in throughput and possibly more relevant than conventional assays.
Together, these approaches will improve public health by providing new insights and assays in preclinical safety testing, disease detection, and patient management. 

Innovative Safety and Technologies Branch

Mission: To develop innovative approaches for assessing the safety of FDA-regulated products and improving the diagnosis and treatment of disease to improve the lives of Americans. Approaches are broad and encompass studies:

a) identifying new biomarkers
b) developing new innovative methods
c) using proven technologies in new applications to improve public health  

These approaches will help improve the speed and accuracy of the assessments and ensure the safe use of FDA-regulated products. 

Additionally, innovative technologies such as in vitro cardiac cell cultures are being evaluated for their ability to assess the risk of tobacco products. 

Personalized Medicine Branch

Mission: To develop biomarkers, technologies, and tools to classify individuals into subpopulations that differ in their susceptibility to a particular disease or their response to a specific treatment. Classifications include:

a) genetics
b) sex
c) age
d) epigenetics
e) life-style and environmental factors such as smoking and obesity

Preventions and therapies can then be chosen that maximize benefits while minimizing side effects and unnecessary treatments and tests. Application of personalized medicine has the potential to improve public health and reduce unnecessary costs.


Liver Toxicity

  • Discovering biomarkers of liver toxicity using a systems biology approach to address weaknesses in preclinical assessment of toxicity
  • Using cell free microRNA (miRNA) as improved clinical biomarkers of drug-induced liver injury
  • Preclinical studies investigating the dose range and proof-of-principle that leflunomide-induced liver injury is enhanced by cytochrome P450 inhibition
  • Assessing acetaminophen-induced liver injury and the influence of dietary supplements-potential synergistic interactions
  • Identification of new mechanistic human biomarkers of adverse responses to acetaminophen

Effects of Potential Endocrine Disruptors

  • Evaluation of reproductive and development effects of oxybenzone

Stem Cells

  • Establishment of mouse embryonic stem cells as an in vitro model to explore developmental toxicity
  • An omics approach to investigate the metabolic and endocrine effects of fructose on adipocytes compared to glucose  
  • Evaluation of stem cell-derived cardiac cells for their ability to assess risk of tobacco products  

Pharmacogenetics and Pharmacogenomics

  • Whole genome sequencing to identify genetic susceptibilities to carbamazepine-induced adverse reactions
  • Genetic effects on clopidogrel and aspirin adverse events
  • Genetic and epigenetic mechanisms of sex differences in the kidney of a rat model system: developing safety biomarkers for FDA-regulated products
  • Development of predictive biomarkers for doxorubicin-induced cardiotoxicity using a systems biology approach

Food and Biological Product Safety

  • Extending the usefulness of a mobile, field-rugged rapid detection technology for select pathogens
  • Rapid screening of food or drugs for chemical or microbiological contamination
  • Rapid and sensitive detection of Creutzfeldt-Jakob disease agents in tissue and blood donations

In silico Approaches to Model Toxicity

  • 3D- and 4D-QSDAR modeling applied to various toxicological endpoints
  • Understanding and predicting immune-mediated idiosyncratic drug reactions using a molecular modeling approach  

Study of Tobacco Toxicity

  • In vitro assessments of the toxicity of tobacco smoke in human lung and cardiac cells using a systems biology approach 

Ongoing Research Projects

  • 3D- and 4D-QSDAR Modeling Applied to Various Toxicological Endpoints (E0734801)
  • An omics approach to investigate the metabolic and endocrine effects of fructose on adipocytes compared to glucose (E0740401)
  • Assessing acetaminophen-induced liver injury and the influence of dietary supplements- potential synergistic interactions (E0737911)
  • Biomarkers of Liver Toxicity (E0732201)
  • Delta Vitamin Obesity Prevention Summer Camp (E0733001)
  • Development and application of a mitochondria-specific gene array (Mitochip) for the investigation of clinical and non-clinical predictive biomarkers of toxicity (E0739701)
  • Development and validation of 3D-QSDAR models for prediction of the binding affinity of chemicals from the ToxCast database to the estrogen receptor (ER) (E0753901)
  • Development of Predictive Mitochondrial Biomarkers for Drug-induced cardiotoxicity using a System Biology Approach (E0733201)
  • Development of the Mouse Embryonic Stem Cell Test (E0741901)
  • Developmental Toxicity of Bitter Orange in Rats (E0214701)
  • Differential liver toxicity profiles and selective binding of green tea epigallocatechin gallate to hepatic proteins in a diverse group of mice from different genetic background (P00775)
  • Dose-Finding Study for Reproductive and Developmental Toxicity Study of Oxybenzone (E0217801)
  • Effect of fetal exposure to oxybenzone on reproductive organs of postnatal day 21 rats (E0745501)
  • Effect of fetal or postnatal exposure to oxybenzone on reproduction in male rats (E0750301)
  • Effect of oxybenzone on embryo/fetal development in Sprague-Dawley rats (Segment II) (E0218701)
  • Effect of oxybenzone on fertility and early embryonic development in Sprague-Dawley rats (Segment I) (E0218601)
  • Effect of oxybenzone on pre and postnatal development in Sprague-Dawley rats (Segment III) (E0218801)
  • Epigenetics, DNA Methylation and Obesity (E0733101)
  • Establishing a mouse model of sex-related differences in doxorubicin-induced cardiac toxicity (P00777)
  • Establishment of Embryonic Stem (ES) Cells as an in vitro Model to Explore Developmental Toxicity (E0735401)
  • Examination of a novel flow cytometer as a diagnostic platform for rapid determination of bacterial antibiotic resistance and the presence of viruses, prions, or parasites in clinical samples (E0746901)
  • Genetic and Epigenetic Mechanisms of Sex Differences in the Kidney of a Rat Model System: Developing Safety Biomarkers for FDA-Regulated Products (E0743901)
  • Genetic Variants in Cardiovascular Disease Risks and Drug Responses: Exome Sequencing and Variant Characterization in the Amish Population (E0752601)
  • Identification of New Mechanistic Biomarkers of Adverse Responses to Acetaminophen (E0731301)
  • Identifying drugs that cause female-biased hepatotoxicity by analyzing FDA drug approval packages/labels and FDA-maintained databases and conducting comparative
    studies in primary hepatocytes of rats, mice and humans (E0750201)
  • Mechanism of Cisplatin-induced Nephrotoxicity (P00765)
  • microRNA as Noninvasive Biomarkers for Tobacco Smoke Associated Bladder Cancer (E0751801)
  • Physiological Effects of Bitter Orange in Rats (E0214901)
  • Preclinical studies investigating the dose range and proof-of-principle that leflunomide-induced liver injury is enhanced by cytochrome P450 inhibition (E0744201)
  • Preliminary Concentration Response Assessments of Tobacco Smoke Condensates in Lung and Cardiac Cells (E0744701)
  • Preliminary Study for Whole Smoke Acute Exposure in Lung Cells (P00781)
  • Rapid and sensitive detection of Creutzfeldt-Jakob disease agents in tissue and blood donations (E0748901)
  • Rapid Screening of Food or Drugs for Chemical or Microbiological Contamination (E0734701)
  • Understanding and Predicting Immune-mediated Idiosyncratic Drug Reactions: Molecular Modeling of Interactions between Drugs, Polymorphic HLA Proteins, and T-cell Receptors (E0739501)
  • Use of New Technologies to Develop Biomarkers of Harm for New Tobacco Products (E0744711)
  • Using cell free microRNA (miRNA) as improved clinical biomarkers of drug-induced liver injury (E0749701)
  • Using Existing Sequencing Data to Identify Genetic Variants Responsible for Corticosteroid-Induced Adrenal Suppression (P00754)
  • Whole-Genome Sequencing to Identify Genetic Susceptibilities to Carbamazepine-Induced Adverse Reactions (E0745301)
  • Yellow Agouti Mouse Breeding Colony (E0728801)


The NCTR Annual Report contains information on the latest accomplishments and plans for the Division of Systems Biology (formerly the Division of Systems Toxicology) 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: 02/18/2015
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