Yongbin Zhang, D.V.M., Ph.D.
NCTR/ORA Nanotechnology Core Facility
Office of Scientific Coordination
National Center for Toxicological Research
Food and Drug Administration
- Ph.D., Toxicology, Oklahoma State University
- D.V.M., China Agricultural University
- FDA experiences: 4 years
- Toxicity, particle-kinetics and dermal penetration of engineered nanomaterials
- Confocal Raman Spectroscopy in nanotechnology and biomedical applications
- Alternative methods for toxicity testing of nano-products regulated by FDA
- Neurotoxicology of chemicals
- Regulatory science.
Proposed Research Project for an FDA Commissioner's Fellow:
Nanotechnology as an emerging technology has been applied in FDA regulated products, such as foods, cosmetics, and medical products. FDA has developed nanotechnology regulatory science program to enhance the nanomaterial characterization, in vitro and in vivo modeling and product- focused research (Hamburg, 2012). The toxicity of nanoparticles depends very much on their shape, size, chemical and surface properties among others (Nel, Science, 2006). Preclinical animal studies to predict toxicity are considered costly and time-consuming, and there are ethical reasons to reduce animal usage. Therefore, establishing a rapid safety screening platform with high throughput and a high predictive rate with few false-positive is urgently needed in nanotoxicity testing. The culture and differentiation of human induced pluripotent stem cells (hIPS) would have three tremendous advantages in detecting early signs of toxicity of nanomaterials: (1) to allow the generation of theoretically unlimited quantities of cells with a range of genotypes; (2) to differentiate to a variety of cell types; (3) to enable the generation of developmental models that cannot be achieved with other cell types.
We have found that TiO2 nanoparticles used in cosmetics are minimally toxic to human mesenchymal stem cells (hMSCs), but alter the differentiation of these cells into adipocytes. The uptake of the TiO2 is through an endocytosis pathway, thus demonstrating that protein interaction with the nanoparticles may play a role in cellular uptake and disposition (manuscript in preparation). Our studies have also demonstrated that carbon nanotubes (made from the same carbon materials as graphene, but with different shapes) have adverse effects on human cells (Zhang et al., ACS Nano, 2010, 2011). This proposal is designed to investigate if graphene can elicit similar effects as TiO2 on human induced pluripotent stem cell differentiation. In this study, we propose using TiO2 nanoparticles and graphene nanomaterials to: (1) evaluate their toxicity in human induced pluripotent stem cell (hIPS) and human mesenchymal stem cell (hMSC) models; (2) evaluate their effects on differentiation in hIPS and hMSC models; (3) detect and quantify the cellular uptake of graphene using confocal Raman microscopy, transmission electron microscope (TEM) and elemental analytical techniques (ICP-MS); (4) explore the possible mechanism with the effect of the nanomaterials on the stem cells. The successful conclusion of this project will quantitatively determine the sensitivity of human induced pluripotent stem cell and human mesenchymal stem cell models to detect early effects of two different types of nanomaterials. In addition, we will establish methods in FDA nanotechnology core facility for the detection of nanomaterials in stem cells.
The FDA Regulatory Science Priority Area for the project is Modernize Toxicology to Enhance Product Safety.
- Ph.D in toxicology, pharmacology, biochemistry or other biomedical sciences.
- Previous experience with cultured cells, especially stem cells, and nanomaterial research is preferred.
Selected Recent Publications:
- Y. Zhang, S. A. Ferguson, A. S. Biris, S. Hussain, S. F. Ali. Effects of silver nanoparticles on body weight and locomotor activity in male Sprague-Dawley Rats. Small. 9(9-10):1715-20. 2013.
- X. Chen, Y. Zhang, J. Yan, R. Sadiq, and T. Chen. Mutation induction by X-ray is inhibited by miR-34a in a P53-dependent manner in human lymphoblastoid cell lines. Mutat Res. 12;758(1-2):35-40.2013
- M Mahmood, Y Xu, V Dantuluri, T Mustafa, Y. Zhang, A Karmakar, D Casciano, S Ali, A Biris Carbon nanotubes enhance the internalization of drugs by cancer cells and decrease their chemoresistance to cytostatics. Nanotechnology 24(4):045102. 2013.
- N. Mei, Y. Zhang, Y. Chen, X. Guo, W. Ding, , S. F. Ali, A.S. Biris, M. M. Moore, and Tao Chen. Silver nanoparticles induced genotoxicity and oxidative stress in mouse lymphoma cells. Environmental and Molecular Mutagenesis. 53, 409-419, 2012.
- Y. Zhang, Y. Xu, Z, Li, T. Chen, S. M. Lantz, P. C.Howard, M. G. Paule, W. Slikker Jr., F. Watanabe, T. Mustafa, A. S. Biris, S. F. Ali. Mechanistic Toxicity Evaluation of Uncoated and PEGylated Single-Walled Carbon Nanotubes in Neuronal PC12 Cells. ACS Nano. 5(9):7020-33, 2011.