Research Expertise and Projects
Project 1: Stem Cells in Nanotoxicity Testing
The use of nanotechnology and engineered nanoparticles (NP) in commercially available products is rapidly increasing. Due to their infinitesimal size, the particles behave according to principles of quantum physics with unique repercussions in the field of medicine and biotechnology; these properties may have profound impacts on human health. Nanotechnology is an inherently interdisciplinary venture with enormous implications and diverse applications (e.g., medicine, energy, materials, agriculture, communications, and electronics).
My laboratory has developed several novel approaches to derive neurons from stem cells and has developed a mutagenesis assay system to assess the risk of nanomaterials on stem cell properties. The study will lead to better understanding of the ways that NPs’ composition, shape, charge, surface chemistry, and particle size relate to the integration of a material into a stem cell’s fate. It will provide novel data describing NP cytotoxicity and mutagenic effects on sensitive stem cell lines. The possible use of this research in refinement of stem cell assays has led to funding support through the National Institute of Environmental Health Sciences.
My work has been published in The Proceedings of the National Academy of Sciences, Nanoletter, among other journals, and has been heavily cited in the field. The results of this research will also provide necessary scientific data to improve or eliminate potential toxicity of NPs and information for relevant authorities when approving products for consumer use.
Project 2: Stem Cell Reprogramming and Transdifferentation
It is well known that cells have a significant degree of plasticity. This plasticity indicates that somatic cells can be reprogrammed into another cell lineage or to stem cells. Recent reports showed that the reprogramming of mouse and human fibroblasts to a pluripotent state can be achieved by ectopic expression of defined factors, such as Oct4, Sox2, Nanog, c-Myc, and Klf4 (or Lin28). Though induced pluripotent stem (iPS) cells are very similar to embryonic stem (ES) cells, their genetic modifications have the potential to activate oncogenes and lead to cancer formation. Reprogramming stem cells without genetic modification and leaving the iPS cells in a genetically pristine state is the next big hurdle for stem cell reprogramming research.
Unlike most stem cell reprogramming systems, my novel research seeks to derive stem cells through the manipulation of cell culture conditions using small molecules. The reprogramming medium will be chemically-defined, safe, animal component free, and thus, suitable for future cell therapy. Furthermore, we are working on direct generation of functional neurons from fibroblasts by chemical methods. Stem cell reprogramming and transdifferentiation could provide a virtually unlimited supply of known genetic background, patient-specific cells for disease modeling, drug discovery, and regenerative medicines.
- Rajanahalli, P., Meyer, M., Zhu, L., Wagner, B. D., Robinson, M. L., King, D. A. and Hong, Y. (2011) Conversion of mouse fibroblasts to sphere cells induced by AlbuMAXI-containing medium. Frontiers in Bioscience 4: 1813-1822.
- Meyer, K. Rajanahalli, P., Ahamed, M., Rowe, J. and Hong, Y. (2011) ZnO nanoparticles induce apoptosis in human dermal fibroblast cells via P53 and p38 pathway. Toxicology in Vitro 25: 1721-1726.
- Ahamed, M., Karns, M., Goodson, M., Rowe, J., Hussain, S., Schlager, J.,and Hong, Y. (2008) DNA damage responses to different surface chemistry of silver nanoparticles in mammalian cells. Toxicology and Applied Pharmacology 233:404-410.
- Zhu, L., Wook C., Dai, L. and Hong, Y. (2007) DNA damage induced by multiwalled carbon nanotubes in mouse embryonic stem cells. Nano Letters, 7(12): 3592-3579
- Xing, H. Y., Wilkerson, D. C., Mayhew, C. N., Lubert E. J., Skaggs H. S., Goodson M. L., Hong, Y. Park-Sarge O. K. and Sarge, K. D. (2005) Mechanisms of hsp70i gene bookmarking. Science 307: 421-423.
- Hong, Y. and Stambrook, P.J. (2004) Restoration of an absent G1 arrest and protection from apoptosis in embryonic stem cells after ionizing radiation. Proc. Nat. Acad. Sci., USA. 101 (40): 14443-8. PMID: 15452351.