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About FDA

July-September 2008


JULY: NCTR RESEARCH HIGHLIGHT


Eli Lilly Selects ArrayTrack™

ArrayTrack™ is a free, publicly available bioinformatics tool developed by the NCTR for FDA research and review of pharmacogenomics data submitted by the sponsors in the Voluntary Genomics Data Submission (VGDS) program. ArrayTrack™ has been expanded to other omics dataset types, and over 100 FDA scientists and reviewers have been trained to use the ArrayTrack™ tools. Recently, Eli Lilly formed an evaluation team of experts for a rigorous review of ArrayTrack™'s:

  • architectural structure
  • functional, quality, and security assessments
  • local installation parameters
  • ability to support Eli Lilly's clinical gene-expression studies

Eli Lilly selected the ArrayTrack™ platform for their clinical gene-expression data storage and baseline analysis and further stated, “The level of commitment demonstrated by the ArrayTrack™ group strengthened our confidence in our ability to work together on some of the current gaps in making ArrayTrack™ fully functional for Lilly scientists.”

The Toxicity of Nanomaterials

Dr. Paul Howard, from the Division of Biochemical Toxicology, and Dr. Syed Ali, from the Division of Neurotoxicity, gave invited presentations at the first United States Air Force Workshop on Biological Interactions of Engineered Nanomaterials. The workshop, held June 24-25, 2008, at Wright-Patterson Air Force Base, was convened to discuss the current and proposed uses of manufactured nanomaterials and the risk to personnel. Specific topics of interest were the distribution of nanomaterials following contamination, the ingestion and potential toxicity of materials through inhalation, the potential for dermal penetration, and the toxicity expressed using in vitro systems. The title of Dr. Howard’s presentation was “Sentinel Organ Approach to Determining Dermal Penetration of Nanomaterials.” Dr. Ali’s talk was titled “Nanoparticles and Nanomaterials: Friends or Foe."

For more information, contact Drs. William Slikker, Paul Howard, or Syed Ali.

Scientists from Korean National Research Institute of Toxicological Research (NITR) at Korea FDA (kFDA) Visit NCTR

On July 15-16, 2008, NCTR was pleased to host scientists, Drs. Sue-Nie Park, Hong-Ki Min, Ki Sook Park, Ho-Sang Jeong, and Wan-Seob Cho, from the NITR/kFDA for a workshop to explore potential for collaborative research. Scientific focus areas discussed included:

  • genomics
  • bioinformatics
  • genotoxicology
  • nanotoxicology
  • National Toxicology Program
  • phototoxicology
  • bioimaging
  • personalized medicine and nutrition

The workshop included presentations, development of an outline for research projects, and a tour of NCTR.

For more information, contact Dr. Weida Tong, Division of Systems Toxicology, NCTR.

FDA Principal Deputy Commissioner and Chief Scientist, Dr. Frank Torti, Visits NCTR July 16-17
On July 16, a meeting in Little Rock with Arkansas with Dr. Torti, NCTR leadership, and academic and federal collaborators provided a forum for Dr. Torti to get a broad overview of NCTR's educational and research collaborations within Arkansas. Collaborators included:
 

  • Arkansas Children’s Hospital
  • Central Arkansas Veterans Healthcare System
  • Philander Smith College
  • U.S. Department of Agriculture
  • University of Arkansas at Little Rock
  • University of Arkansas at Pine Bluff
  • University of Arkansas for Medical Sciences

On July 17, the NCTR senior scientists met with Dr. Torti to discuss current and future research. After a tour of the Center, NCTR working groups on Bisphenol A and nanotechnology (including Arkansas Regional Laboratory) also met with Dr. Torti, followed by an All-Hands meeting. Prior to his departure, Dr. Torti gave opening remarks at the Food Protection Plan research planning meeting at NCTR.

For more information, contact Dr. William Slikker, Director, NCTR.


AUGUST: NCTR RESEARCH HIGHLIGHTS


Increased Recycling and Reduced Environmental Emissions
The NCTR Office of Regulatory Compliance and Risk Management (RCRM) is instituting a major program to transform waste-management practices at the Jefferson Laboratories. The new waste-management system will provide significant benefits in both financial costs and environmental impacts. NCTR will suspend the use of the on-site waste incinerator reducing air emissions and saving the cost of natural gas used to operate the unit. The program also increases waste minimization practices by increasing recycling efforts – primarily in cardboard, glass, and paper products. These activities are an element of the recently developed Jefferson Labs Environment, Safety and Health Management System (ESHMS) and will be managed in accordance with international/national standards that are incorporated in the ESHMS.

FDA Principal Deputy Commissioner and Chief Scientist, Dr. Frank Torti, Stresses Importance of FDA's Food Protection Plan
NCTR scientists, in a conference call with representatives from the Office of the Commissioner, met last week at NCTR to develop a short- and long-term research agenda to support the FDA's Food Protection Plan (FPP).

Dr. Frank Torti opened the conference call noting that supporting the FPP with strong research was an important activity for FDA. Current research initiatives were examined in light of current and emerging food safety problems. Research projects that fulfill the research needs identified in the FPP were outlined. In addition, the researchers identified four research areas that will be further developed to support food protection in the future:
 

  • Fundamental and applied food microbiology
  • Analytical methods development
  • Computational science and bioinformatics
  • Predictive toxicology

For further information, please contact Dr. Margaret A. Miller or Dr. William Slikker, Director, NCTR.

Developing the Path to Personalized Nutrition and Medicine Using Community-Based Participatory Research (CBPR)
Advances in experimental technologies for analyzing genomes, proteins, metabolites, and RNA transcripts are laying the foundation for developing recommendations for personalized nutrition and optimizing medical treatments for each individual. However, current experimental strategies for identifying the risk of carrying a gene variant linked to a disease rely on studies that yield the average risk for a population. Similarly, the risk associated with eating a particular nutrient is also derived from the association of the amount of that nutrient eaten and the incidence of disease in the population. Developing research strategies that determine individual risk factors for inheriting a gene variant (e.g., single nucleotide polymorphism) or an individual's exposure to certain nutrients or foods is a challenge for developing personalized medicine and nutrition. One approach to this challenge is to monitor participants in a study that involves more than the usual single event where blood is drawn and diet history is recorded. NCTR’s Division of Personalized Nutrition and Medicine (DPNM) has entered into an Interagency Agreement (IAG) with the USDA Agricultural Research Service (ARS) in Little Rock, Ark., to conduct community-based participatory research (CBPR) in Marvell, Ark.

The pilot CBPR project was conducted at a Summer Obesity Prevention Camp held at the Boys, Girls, and Adults Community Development Center (BGACDC - http://www.bgacdc.net). School-age children (6-14 yrs) from Marvell, Ark. and Elaine, Ark. participated in the day camp, which focused on nutrition, education, and physical activity. The children were provided breakfast and lunch with an emphasis on fruits and vegetables. A subgroup of the children and their caregivers participated in a biomedical research project that analyzed vitamins in serum before, at the end, and one month after the summer camp. The results of the vitamin analyses will be known in mid-Fall 2008.

The program is a pilot project for introducing biomedical research to the Arkansas Phillips County community. Additional studies involving school-age children and the adult population are planned for 2009. The concepts of using CBPR in biomedical research have been described in the following publication currently in press: Beverly McCabe-Sellers et al., (2008) Personalizing Nutrigenomics Research Through Community Based Participatory Research and Omics Technologies, Omics, A Journal of Integrative Biology.

For more information, contact Dr. Jim Kaput, Director, Division of Personalized Nutrition and Medicine, NCTR.

Antibiotic Resistant Staphylococcus aureus
NCTR scientists have developed technologies for the detection and quantification of proteins expressed by Staphylococcus aureus in an effort to identify candidates that could potentially be used as targets for the development of novel therapeutic approaches for the prevention and treatment of diseases caused by antibiotic resistant S. aureus.

To date, one-dimensional polyacrylamide gel electrophoresis (1D-PAGE) followed by nanocapillary liquid chromatography coupled with mass spectrometry (nanoLC-MS/MS) has been used to analyze proteins of S. aureus. This approach has identified 1,263 staphylococcal proteins. In addition, the relative abundance of proteins was determined using a quantitative value termed, normalized-peptide number; and overall, proteins known to be cell wall-associated were more abundant early in growth, while proteins known to be secreted into the surrounding milieu were more abundant late in growth. The use of 1D-PAGE, followed by nanoLC-MS/MS, offers a means to generate comprehensive protein profiles of antibiotic-resistant S. aureus, and bacteria, in general, for the purpose of identifying proteins critical for disease and/or essential for bacterial viability. These profiles, in turn, can then be used to develop alternatives, such as passive immunization, in lieu of or in conjunction with antibiotic therapy for the prevention and treatment of diseases caused by S. aureus.

This research allows the Interagency Task Force on Antimicrobial Resistance, co-chaired by the Centers for Disease Control and Prevention, the Food and Drug Administration, and the National Institutes of Health to provide the research community with genomics and other powerful technologies. These tools will aid the development of new rapid-diagnostics methodologies, novel therapeutics, and interventions to prevent the emergence and spread of resistant pathogens and encourage basic and clinical research in support of the development and appropriate use of vaccines in human and veterinary medicine in partnership with academia and the private sector.

For further information, please contact Drs. Mark E. Hart or Carl E. Cerniglia at NCTR; or see R.C. Jones, et al., J. Bacteriol, 190: 5265-5278, 2008.

Science Advisory Board Meeting at NCTR
The National Center for Toxicological Research (NCTR) held a Science Advisory Board Meeting in Jefferson, Arkansas, on August 12 and 13. In attendance were all members of NCTR’s Science Advisory Board, representatives from the Office of the Commissioner, each of the Product Centers, a member of FDA’s Science Board, the University of Arkansas Little Rock, and the University of Arkansas for Medical Sciences (UAMS).

On August 12, the NCTR Divisions provided the following updates: current research activities focusing on major finds of the past year, their importance, and major issues associated with their current research.

The Site-Visit Subcommittee Chair presented the visit review of the Division of Biochemical Toxicology, which occurred in April 2008.

  • Upon acceptance of the report by the Full Committee, the Biochemical Toxicology Director provided his response to the main issues and recommendations made by the site-visit team.

The Site-Visit Subcommittee Chair for the Division of Microbiology then presented the visit review, which occurred in August 2007.

  • Upon acceptance of the report by the Full Committee, the Microbiology Division Director provided his response to the main issues and recommendations made by the site-visit team.

The group meeting continued August 13, 2008, at UAMS. Dr. Slikker provided a center-wide update on scientific activities and discussed the NCTR alignment and strategic focus. Each of the FDA representatives had an opportunity to address their research needs and collaborative opportunities, including the consideration of future NCTR research issues. The meeting concluded with recommendations for follow-up actions by NCTR.

For further information, please contact Dr. Margaret Miller, Associate Director for Regulatory Activities, NCTR.

Critical Path—Noninvasive Imaging
NCTR scientists have completed trial experiments in the new NCTR MicroPET Imaging Center investigating whether, early in development, anesthetic exposures alter patterns of normal programmed cell death. PET, or Positron Emission Tomography, is most commonly known for its use in oncology clinics to detect tumor masses and follow the course of disease and treatment effects. However, PET also is highly versatile in monitoring changes in body metabolism in health and disease through use of a variety of positron-emitting radiochemicals. Utilization of the NCTR facility is enhanced through cooperation with the nearby University of Arkansas for Medical Sciences cyclotron facilities that provide the short half-life radiochemicals required for this work. Use of MicroPET, which is configured specifically for very high quality imagery in small animals and other imaging techniques, will provide the FDA with noninvasive procedures for repeatedly monitoring and detecting the time-course of rarer toxicological events that may have direct applications in clinical settings.

For further information, contact Dr. Merle Paule, Director, Division of Neurotoxicology or Dr. William Slikker, Jr., Director, NCTR.


SEPTEMBER: NCTR RESEARCH HIGHLIGHTS


Records Control Schedule Approved
The revised NCTR Records Control Schedule received final approval July 30, 2008 when the SF-115 was signed by the U.S. Archivist. The revised schedule includes NCTR Program Records, GLP (Good Laboratory Practice) experiment records, GCP (Good Clinical Practice) experiment records, technical reports, environmental and health records, and a variety of database records. The NCTR Records Management Staff will develop and present a series of training sessions to inform all employees of these new requirements. The goal is to implement an active and continuing program that ensures compliance with federal regulations for the creation, use, maintenance, and disposition of the Center’s federal records. Federal records must be stored in such a way that they are both sufficiently accessible and are safeguarded against loss. To meet federal requirements for the safekeeping of records, a new NCTR Records Repository and Archives is scheduled to be complete by October 2008.

For more information, contact Jennings “Cody” Partridge, Associate Director, Regulatory Compliance and Risk Management, NCTR.

Novel Methodology Supporting Rapid Detection of Bacterial Food Contaminants
NCTR mathematicians have developed a novel algorithm to predict the optimal testing range and then identify characteristic bacterial genes found in comparative genomic microarray (“gene chip”) technologies that are proposed for rapid detection of food contamination. The novel statistical technology, known as change-point estimation, relies upon finding an optimal graphical representation from multiple data points in noisy systems (multivariate adaptive regression spines). It has outperformed existing algorithms for specificity and accuracy in the analysis of two publically available data sets. Comparative genomic analysis for bacterial contaminants in foods requires more advanced statistical techniques because of a high probability that food samples may simultaneously contain several different species.

For further information, contact Dr. James Chen, Division of Personalized Nutrition and Medicine, NCTR.

Critical Path Initiative

Seven NCTR scientists presented their research programs at the Drug Information Association Critical Path Symposium held September 15-16 in Bethesda, Maryland. The presentations were grouped under three NCTR strategic initiatives: 1) increased productivity for pre and postmarket activities; 2) translational biomarkers of toxicity/safety; and 3) noninvasive and minimally invasive technologies for safety evaluation.

Specific interests included:

  • development of standards for data warehousing and the e-submissions process
  • exploration of idiosyncratic liver injury through comprehensive omics approaches
  • preclinical/clinical imaging with microPET/PET and MRS/MRI technologies
  • development of a mutation assay (PIG-A) for preclinical, clinical, and postmarket safety
  • establishment of an international consortium for Type II diabetes and gene/diet interactions

Jefferson Laboratories World Fest
International diversity was celebrated at Jefferson Laboratories on September 18 as employees shared the color, music, traditions, and food from 15 countries. This year five new displays were added representing the culture of different states. The annual event has become popular on campus with each booth presenting samples of traditional recipes.

For further information, contact Dr. William Slikker, Jr., Director, NCTR.

Contact FDA

870-543-7000
National Center for Toxicological Research

Food and Drug Administration

3900 NCTR Road

Jefferson, AR 72079