Division Director: William B. Mattes, Ph.D., DABT
About the Division
The division focuses on the development and evaluation of new technologies and the identification of new biomarkers (disease indicators) to support the FDA's mission. The division's mission is to address problems of food, drug, and medical-product safety using systems biology approaches and innovative technology:
- Translational Safety Biomarkers and Mechanisms
- Alternative Models to Assess Drug Safety
- Technology to Assess Product Safety
- Computational Modeling
- Cross-species Predictions and Translation
- Translational prognostic and/or predictive biomarkers for improving pharmaceutical product safety
- Delineated mechanisms for 1) species, tissue, sex, and sub-population specificity in drug toxicity, 2) opioid addiction, and 3) next-generation pharmaceutical toxicity
- In vitro models to evaluate reproductive, developmental, and clinical toxicity
- In silico models for predicting relevant toxicities
- Robust technologies for drug adulteration/compounding
- Use as a tool, classes of drugs with known toxicities such as anthracyclines, tyrosine kinase inhibitors, oligonucleotide therapeutics
- Characterize systems-biology effects with state-of-the-art tools: mRNA and miRNA transcriptomics, epigenomics, metabolomics, proteomics, lipidomics, and imaging
- Integrate data with systems-biology informatics accounting for species, tissue, sex, and sub-population differences
- Incorporate innovative in vitro, computational and instrumental technology e.g. MALDI imaging
Biomarkers of Doxorubicin-Induced Heart Injury
NCTR scientists developed and used a mouse model of DOX-induced heart injury to identify two proteins (NOTCH1 and vWF) that were elevated in plasma prior to the release of cardiac-specific injury marker, troponin T, in plasma and development of pathology in the heart. Increased level of both proteins was mitigated when toxic effects of DOX were diminished in the heart in mice that received a cardioprotective drug, dexrazoxane, suggesting these proteins as candidate early markers of DOX cardiotoxicity. These early protein markers of DOX-induced heart injury with potential applications in the clinic for monitoring and/or predicting cardiotoxicity induced by DOX will help design more effective treatment regimens. These results have been published in Toxicology and Applied Pharmacology.
Development of a Mouse Testis Organ System
The potential for medicines to have adverse effects on male reproductive capacity remains a concern in drug development. While animal tests have been useful, faster methods would be desirable. At the meeting titled “FutureTox IV Progress to Maturity: Predictive Developmental and Reproductive Toxicology for Healthy Children,” scientists from NCTR and CDER presented results of a new in vitro assay where a mouse testis organ system is used to examine the toxicity of chemicals. Further results have been published in Birth Defects Research.
2019 Select Accomplishments
- An Integrated Analysis of Metabolites, Peptides, and Inflammation Biomarkers for Assessment of Preanalytical Variability of Human Plasma. Publication in Journal of Proteome Research.
- Use Cases, Best Practice and Reporting Standards for Metabolomics in Regulatory Toxicology. Nature Communications.
- Evaluation of the Performance of Lipidyzer Platform and Its Application in the Lipidomics Analysis in Mouse Heart and Liver. Publication in Journal of Proteome Research.
- Candidate Early Predictive Plasma Protein Markers of Doxorubicin-Induced Chronic Cardiotoxicity in B6C3F1 Mice. Publication in Toxicology and Applied Pharmacology.
- Testicular Function in Cultured Postnatal Mouse Testis Fragments is Similar To That of Animals During the First wave of Spermatogenesis. Publication in Birth Defects Research.
- Determined the Sensitivity of CD-1 and CF-1 Mouse Strains to Morphine and Methadone and Whether Exposure During Gestation Leads to the Development of Neural Tube Defects.
- Investigated the Effects of Opioid Exposure on Neural Precursor Differentiation Using a Human Induced-Pluripotent Stem Cell Model.
2020 Select Research Projects
- Investigation of the Mechanistic Aspects of Sex-Based Differences in Susceptibility to Doxorubicin-Induced Cardiac Toxicity in Mice
- Predict Tyrosine Kinase Inhibitor (TKI) -Induced Cardiotoxicity Using Induced Pluripotent Stem Cell-Derived Cardiomyocytes
- Verification of Novel Predictive Biomarkers of Doxorubicin-Induced Cardiotoxicity in Breast Cancer Patients
- SpecID for Organic Chemical Characterization
- Evaluation of an In Vitro Mouse Testis Organ Culture System for Assessing Testicular Toxicity
Resources for You
- NCTR Grand Rounds: "Overview of FDA's Perinatal Health Center of Excellence: Development and Validation of Predictive Systems" (Presentation recorded in Adobe Connection on July 13, 2019)
- Perinatal Health Center of Excellence (PHCE)
- Annual Report
- Meet the Principal Investigators
- MitoChip: An NCTR-Developed Mitochondrial Research Tool
- National Center for Toxicological Research
Food and Drug Administration
3900 NCTR Rd
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