Vol. 10, Issue 1: Jul-Sept 2014
NCTR Welcomes New Director of Jefferson Labs NanoCore
Anil K. Patri, Ph.D., joined NCTR as the Director of FDA’s Jefferson Labs Nanotechnology Core Facility (NanoCore) in August, 2014. Dr. Patri brings to the FDA a wealth of experience and knowledge in nanomaterial manufacture, characterization, detection in complex matrices (e.g. cells), and behavior in biological matrices. Prior to coming to NCTR, Dr. Patri served as the Deputy Director of the National Cancer Institute’s Nanotechnology Characterization Laboratory (NCI/NCL) in Frederick, MD. The mission of NCI/NCL is to conduct the preclinical characterization of nanomaterials destined to be submitted to FDA as cancer chemotherapeutics.Under his guidance, the NCI/NCL developed a nanomaterial characterization cascade, specific methodologies, and standards in collaboration with other government partners.
The combination of his 10-year experience at NCI/NCL together with his knowledge of nanomaterial manufacturing, characterization, and toxicity uniquely qualifies Dr. Patri for this position to lead the Jefferson Labs Nanocore. NCTR is very pleased to have Dr. Patri on board and is excited to draw on Dr. Patri’s experience to accomplish FDA goals.
Effect of Silver Nano-particles on the Gut Microbes and Intestinal Immune Responses
NCTR scientists have shown that silver nanoparticles, administered by oral gavage, caused size- and dose-dependent changes in the gastrointestinal microbiota and the gut-associated immune response of rats; with smaller nanoparticles demonstrating the greatest antimicrobial capability. Silver nanoparticles are widely used in the food and health care industry due to their antimicrobial properties. However, the effects of oral ingestion of nanosilver are largely unknown. This study suggests that the microbiome may need to be considered in the safety evaluation of nanotechnology-derived products. This would be added to traditional metabolism, toxicity, and tissue-deposition information currently used in toxicology risk assessments. This study, which is part of a National Toxicology Program 13-week study, is currently published online atNanotoxicology.
An Empirical Method for Predicting Toxicity?
Scientists from NCTR and the Center for Drug Evaluation and Research developed a novel toxicity modeling approach utilizing 3D NMR-distance based descriptors to identify unique structural alerts (toxicophores) associated with phospholipidosis (PLD). PLD is a common side effect of many drug classes; however, there is a lack of understanding of its molecular mechanism. The 3D-SDAR PLD classification model was based on a training dataset of 328 compounds with publicly available information and was validated on external (proprietary FDA dataset of 294 drugs) and hold-out test sets (20% of training). The classification accuracy for the external test set was 70%. This in silico modeling approach could be utilized to predict which new compounds have a potential to induce PLD. The approach could also be adapted as a general-purpose tool to discover structural alerts for other drug side effects and to design new and safer drugs. A manuscript describing the method isavailable online at Bioorganic & Medicinal Chemistry.
NCTR Scientists Win Video Award
Two NCTR scientists, Trisha Eustaquio, Ph.D. and Angel M. Paredes, Ph.D. were the recipients of one of two video awards from the Federation of American Societies for Experimental Biology (FASEB). Mitochondria are the powerhouses of the cell. This video shows an animation of 3D mitochondria data in a healthy neuron from a rat brain collected using serial block-face scanning electron microscopy (SBF-SEM). First, the SBF-SEM scans are displayed, which are then computed to identify the cell surface (green), mitochondria (each shown in a different color), and nucleus (semi-transparent purple). In a healthy cell, the mitochondria are often elongated, reaching out to network with other mitochondria to optimize energy output, as seen in this video.
The ten images and two videos that received awards demonstrate the breadth of ongoing research in the biomedical and life sciences. Winning entries were unveiled on FASEB’s website and will be exhibited at the National Institutes of Health..-.
NCTR Welcomes New Director, Systems Biology Division
William B. Mattes, Ph.D., DABT, joined NCTR as the Director, Division of Systems Biology on July 28. In his new position, Dr. Mattes will provide leadership, managerial oversight, and direction for research-related activities within the division. Dr. Mattes received his Ph.D. in Biological Chemistry from the University of Michigan and has over twenty years of experience in chemical and drug development. He is a Diplomate of the American Board of Toxicology with extensive professional experience as a research toxicologist and most recently served as Founder and Principal at PharmPoint Consulting. He was responsible for services supporting safety-issue resolution, technology application, consortium development, biomarker implementation and regulatory relevance, divergent data analysis, and preclinical drug development. Prior to his consulting work, he was the first Director of the Predictive Safety Testing Consortium of the Critical Path Institute where he organized a large consortium of pharmaceutical companies and led the initiative that resulted in CDER's first qualification of predictive biomarkers through their Biomarker Qualification Program. Dr. Mattes was selected to establish and lead a worldwide Center for Excellence in Toxicogenomics and he also led the Database Development team for the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute's Toxicogenomics Committee. Subsequently, Dr. Mattes' unique accomplishments in leading national and international collaborative teams makes him ideally suited to direct and coordinate research activities within NCTR and across FDA.
On August 21-22, 2014, the Global Summit on Regulatory Science (GSRS14) with the theme of “Regulatory Genomics and Beyond” was hosted by FDA and the Canadian Food Inspection Agency in Montreal, Canada. The summit included speaker sessions to explore the applications and regulatory aspects of genomics. The international conference provided an opportunity for scientists from government, industry, and academia from 15 countries to discuss innovative technologies and partnerships to enhance translation of basic science into regulatory applications within the global context. Prior to the summit, the Executive Committee of the Global Coalition for Regulatory Science Research (GCRSR) representing many government regulatory agencies from 9 different countries or regions were briefed on progress from the Bioinformatics, Exposome, Nanotoxicology, and Emerging Technologies Working Groups; and discussed future GCRSR goals for training and collaborative research, and options for the GSRS15 which will be held in Parma, Italy on October 12-13, 2015.