About the Division

Mission

Address regulatory research needs, knowledge gaps, and emerging health threats in regulatory science using systems-biology approaches and innovative technologies of regulatory interests, such as (1) safety and use of medical products (i.e., drugs, biologics, and devices), (2) safety of regulated foods and supplements, (3) safety and detection of components and impurities in regulated products, and (4) develop technological standards and methods used in regulatory science.

Branches Within the Division

DSB is comprised of the immediate office and two branches:

Research Interests

• Mechanisms of Toxicology and Susceptibility to Adverse Effects
• Systems and Organ Toxicological Areas
• Reproduction, Development, and Fertility 
• Drug Addiction and Psychoactive Effects
• Methodologies, Diagnostics, and Models for Regulatory Science Applications

Strategies

• Characterize systems biology and toxicology with state-of-the-art tools:
  • Transcriptomics, epigenomics, metabolomics, proteomics, lipidomics, and imaging
  • Human-based new alternative methodologies (NAMs) 
  • In vivo disease and pharmacodynamic models 
• Utilize pharmacological tools — drug classes with known effects (e.g., anthracyclines, tyrosine kinase inhibitors, opioids, etc.)
• Incorporate innovative computational and instrumental technology 
• Integrate data with systems-biology informatics 
  • Evaluate differences in risk and toxicology related to species, tissue, sex, and sub-populations

Select DSB Accomplishments in 2021

COVID-19 Response

• DSB — with the help of NCTR Center leadership — recruited funding for two Broad Agency Announcement (BAA) contracts that enable NCTR scientists to 1) conduct Biosafety Level 3 studies with SARS-CoV-2 viral strains at the Regional Biocontainment Laboratory at the University of Tennessee Health Science Center (USTHSC), and 2) correlate Matrix-Assisted Laser Desorption-Ionization (MALDI)-imaging mass spectrometry data from COVID-19 infections (human and animal models) with high-powered broadband coherent anti-stokes Raman scattering (BCARS) imaging technologies at Georgia Tech. Research data resulting from these BAA contracts with UTHSC and Georgia Tech are expected to make significant impacts in scientific areas related to:

  Despite the ongoing pandemic and associated limitations related to the number of on-site staff and supply deliveries, DSB scientists published 18 research articles, presented at 12 national and international scientific conferences, provided consults to and collaborated with FDA product centers, supported projects led by other NCTR research divisions, and initiated 9 studies to address COVID-19 knowledge gaps.

  • SARS-CoV-2 infection
  • Host-immune responses
  • Therapeutic combinations
  • Perinatal risks
  • Disease pathogenesis
  • Therapeutic risks
  • Variant cross-reactivity of vaccine targets
  • Potential biomarkers
     
• Scientists within DSB and NCTR's Division of Bioinformatics and Biostatistics collaborated in using homology modeling computational chemistry to identify key interactions between the SARS-CoV-2 infection co-receptor angiotensin converting enzyme 2 and the full-length spike protein trimer of SARS-CoV-2 (Frontiers in Chemistry).

Select 2021 DSB Publications

Renal Toxicology

• Discovery of Novel Proteomic Biomarkers for the Prediction of Kidney Recovery from Dialysis-Dependent AKI Patients.

• Serum Metabolite Profiles Predict Outcomes in Critically Ill Patients Receiving Renal Replacement Therapy.

Prostate Cancer

• Identification of Altered Proteins in the Plasma of Rats With Chronic Prostatic Inflammation Induced by Estradiol Benzoate and Sex Hormones. 

• Altered Expression of Genes Identified in Rats With Prostatic Chronic Inflammation in a Prostate Spheroid Model Treated by Estradiol/Testosterone. 

Cardiotoxicology

• Improving Cardiotoxicity Prediction in Cancer Treatment: Integration of Conventional Circulating Biomarkers and Novel Exploratory Tools.

• Doxorubicin-Induced Delayed-Onset Subclinical Cardiotoxicity in Mice. 

Technology and Methods

• Progress Towards an OECD Reporting Framework for Transcriptomics and Metabolomics in Regulatory Toxicology.

• Metabolomics as a Truly Translational Tool for Precision Medicine. 

• Characterization of Phosphorylated Proteins Using Mass Spectrometry.

• MALDI Imaging Mass Spectrometry: An Emerging Tool in Neurology.

• Emerging Technologies and Their Impact on Regulatory Science.

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2022 Select Research Projects

As a result of outreach efforts, several project proposals were initiated and/or planned for development in 2022, including studies in the following topics:

• COVID-19
• Vaccines
• Cannabinoids
• Cystic fibrosis transmembrane conductance regulator (CFTR) modulators

In addition, opportunities for new collaborations with academia and access to clinical samples, such as multisystem inflammatory syndrome in children (MIS-C) pediatric samples, were also initiated, which will complement ongoing studies and create opportunities for new projects that will contribute to the NCTR and FDA missions.

Resources for You

• DSB Fact Sheet
• 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
• About the National Center for Toxicological Research