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January - March 2009
JANUARY 2009 NCTR HIGHLIGHTS
Modernizing Tools for Safety Assessment
Fifty scientists from the FDA, EPA, CDC, and NIH convened at the 2nd Inter-Agency Computational Toxicology Colloquium held at NCTR on December 10 and 11, 2008. Three major initiatives were selected for development into cross-agency research proposals:
- Development of in silico compound screening and prioritization models for liver toxicity in both animals and humans
- Development of high-throughput screening data-based approach for chemical mixture component grouping, toxicity endpoint prediction, and risk/safety assessment
- Use of high-information content data, such as microarray data, to predict individual susceptibilities and population risk to chemicals and drugs
Written proposals for the in silico modeling and draft documents for chemical mixtures analysis initiatives are circulating among participant agencies for comment.
The Human Variome Project (HVP)
NCTR participated in the HVP planning meeting convened by the Genomics Disorders Research Centre in Melbourne, Australia. The HVP will systematically collect mutations that cause human disease and create the cyber infrastructure to link locus-specific databases to international databases such as the NIH Center of Biotechnology Information and the European Bioinformatics Institute. These efforts will generate datasets necessary for linking individual genetic variation to responses to food, environmental influences, medical treatments, and drugs. The HVP is recognition that significant population differences to the existing genome consensus sequence drive the differences in personalized nutrition and medicine. (In press; Kaput et al. Human Mutation 2009).
For more information, contact Dr. James Kaput, Director, Division of Personalized Nutrition and Medicine, NCTR.
Hepatotoxicity Working Group
The first meeting of the Hepatotoxicity Working Group was held at NCTR on Friday, January 16, 2009. Future areas of potential research and collaboration were discussed including one possible study involving data from multiple types of omic platforms from a number of compounds. This study could lead to biomarkers that would improve the detection of idiosyncratic drugs and lead to clues as to a drug’s mechanism underlying its ability to induce toxicity of an idiosyncratic nature.
For more information, contact Dr. Donna Mendrick, Director, Division of Systems Toxicology, NCTR.
Retirement and Change in FDA Liaison to NTP
William T. Allaben, Ph.D., retired from the National Center for Toxicological Research (NCTR) effective January 3, 2009. Dr. Allaben served the public and the U.S. Government for a total of 36 years, with 33 of those years at the FDA/NCTR and was awarded the DHHS Career Achievement Award from Secretary Levitt. In 1992, Dr. Allaben was instrumental in founding the FDA-NCTR/NIEHS National Toxicology Program (NTP) Interagency Agreement (IAG), and he served as FDA’s Liaison to that IAG for 17 years. Dr. Allaben organized the FDA Chemical Selection Working Group, which forwards nominations to the NTP. All studies reviewed at the biannual Toxicology Study Selection and Review Committee meetings, chaired by Dr. Allaben and the NTP IAG Project Officer, Dr. John Bucher, included key personnel from all FDA Centers, NIEHS, EPA, NIH, and invited subject-matter experts from industry and academia. Under Dr. Allaben’s leadership, NCTR has worked with the NTP to provide FDA regulatory scientists with valuable scientific data on 31 compounds. Dr. Paul C. Howard succeeded Dr. Allaben as FDA’s Liaison of the NTP IAG effective January 2009.
FEBRUARY 2009 NCTR HIGHLIGHTS
New Records Storage Facility
The NCTR Federal Records Schedule has been revised, approved, and published. The kickoff phase will begin in March with a series of training sessions for all employees. These sessions, presented by representatives from the National Archives and Records Administration (NARA) and the NCTR Regulatory Compliance and Risk Management staff, will provide a general overview of Federal Records Management guidelines and specific information about NCTR’s revised record schedules.
In concert with the implementation of NCTR’s revised record schedule, NCTR records are being moved into the newly constructed Records Storage Facility. This 7,000 sq. ft. facility was designed to accommodate NCTR’s scientific, financial, and administrative records in compliance with NARA guidelines. During the move, NCTR Records Management staff will verify record inventories and review disposition dates in accordance with the new schedule.
For more information, contact Jennings Partridge, Associate Director, Regulatory Compliance and Risk Management, NCTR.
Science Advisory Board Review
A site-visit team from the NCTR Science Advisory Board (SAB) met at NCTR on February 18-19, 2009, for an in-depth analysis of research programs within the Division of Systems Toxicology. The site-visit team — led by SAB member, Dr. Cynthia Afshari — was comprised of subject experts from academia, industry, National Institutes of Health, and Environmental Protection Agency. Representatives from each of the other FDA Centers, Office of Commissioner, and Office of Regulatory Affairs actively participated to provide scientific and regulatory advice and to enhance FDA-wide communication.
Scientists from the Division of Systems Toxicology presented results and future plans for studies on biomarker identification, food safety (rapid identification of contaminants), personalized therapies, bioinformatics, and electronic submission. The Division is composed of the following six interactive Centers of Excellence working together to integrate biologically based systems, chemistry, engineering, and computational science:
- Functional Genomics
- Innovative Technologies
The site-visit report will be formally presented at the full NCTR Science Advisory Board meeting to be held at NCTR on November 17-18, 2009. For more information, contact Dr. Donna Mendrick, Director, Division of Systems Toxicology or Dr. William Slikker, Jr., Director, NCTR.
Food Safety Research—DNA Microarray Technology
NCTR scientists, in collaboration with USDA and West Virginia University, have used DNA microarray technology to identify genes responsible for mitigating drug resistance in different species of Salmonella. The microarray biochip can detect up to 775 antimicrobial resistance genes in Salmonella from different classes of drugs, including:
- sulfa drugs
The ability of this high-density technology to rapidly detect hundreds of antimicrobial resistance genes can be beneficial to the FDA, state, and other federal agencies for analyzing patterns of drug resistance in Salmonella and observing emerging drug-resistant species of Salmonella.
For further information, please contact Dr. Rajesh Nayak or Dr. Carl E. Cerniglia, Director, Division of Microbiology, NCTR.
MARCH 2009 NCTR HIGHLIGHTS
Food Defense—Enzyme-Activity Assay
NCTR scientists developed a novel, quantitative, enzyme-activity assay for detecting the ribosome-inactivating enzyme activity that is shared by ricin, abrin, shiga toxin, and shiga-like toxins. This sensitive assay detects very small amounts of ribosome-inactivating protein reaction products using quantitative real-time PCR technology. Naturally occurring plant toxins (ricin and abrin) and shiga-like toxins, which are produced by some E. coli strains (e.g., O157:H7) can be isolated easily. They have been designated as Category B Select Agents by HHS because of their potential exploitation by bioterrorists to poison the food supply chain. Additional studies are being conducted to increase the sensitivity and expand the reliability of the assay in complex food matrices.
For further information, contact Dr. William Tolleson, Division of Biochemical Toxicology, NCTR, or Dr. Frederick Beland, Director, Division of Biochemical Toxicology, NCTR.
Quality Control of Next-Generation Sequencing
The FDA-led MicroArray Quality Control (MAQC) project held its 11th face-to-face meeting on March 9-10, 2009, in Little Rock, Arkansas, with the focus on the quality control of next-generation sequencing, a revolutionary technology for the high-throughput deep sequencing of DNA and RNA samples. Next-generation sequencing will play a critical role in realizing the great potentials of predictive and personalized medicine by providing more accurate genomic information on individual patients. Genomic data generated from this technology will soon be submitted to the FDA by sponsors to support medical product development. As the third phase of the MAQC project, the Sequencing Quality Control (SEQC) project effort aims to objectively assess the technical performance of next-generation sequencing and to address bioinformatics challenges in analyzing the massive sequence data. Over 50 people from 30 organizations participated in the meeting and discussed study design, results from preliminary data sets, and project timeline.
For further information, contact Dr. Leming Shi, Division of Systems Toxicology, NCTR.
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