Dr. Sakaguchi, Professor, received his B.S. in Biology and Ph.D. in Neurobiology from the State University of New York-Albany. After serving as a postdoctoral scholar and research biologist at the University of California-San Diego, Dr. Sakaguchi joined the faculty at Iowa State University as an Assistant Professor. He has served as Chair of the Interdepartmental Graduate Program in Neuroscience here at ISU, and is currently an Adjunct Professor of Biomedical Science at the Iowa State University College of Veterinary Medicine.
My research interests focus on developing experimental strategies for brain rescue and repair. As a potential therapy for treatment of neurodegenerative diseases, stem cells and neural progenitor cells (NPCs) have been proposed as unique sources of transplantable cells to provide neuroprotection to the remaining nervous system elements and to replace degenerating neurons and glia. We are using this strategy and are evaluating the survival, differentiation and integration of NPCs and stem cells transplanted into normal and damaged rodent retinas used as models of retinal degeneration and glaucoma. In addition to cell replacement, another powerful application for stem cells in the retina is gene delivery. For example, neurotrophic factors are known to have protective effects on damaged neurons that would otherwise not survive. Engineering stem cells to serve as vehicles for delivery of neurotrophic factors is a novel and exciting approach as a treatment strategy for blinding ocular diseases and other neurodegenerative disorders (including traumatic brain injury and nerve regeneration). In addition to NPCs, the multipotent nature of bone marrow-derived stem cells (MSCs) makes them attractive candidates for cell-based therapies. We have genetically engineered MSCs to produce and secrete bioactive neurotrophic factors for delivery to the injured CNS. Moreover, the MSCs may be used for autologous transplantation and therefore minimize the likelihood of immune rejection of the grafted cells. Engineering stem cells ex vivo for retinal repair strategies may ultimately provide a reliable means of long-term delivery of therapeutic factors.
Another research focus of the Sakaguchi lab is using integrative neuroprotective and neuroregenerative strategies to study peripheral nerve regeneration and traumatic brain injury. This research aims to develop experimental strategies to repair the damaged nervous system using biomaterials and biodegradable polymers; bioactive molecules; and stem cells.
- A.D. Sharma, P.A. Brodski, E.M. Petersen, M. Dagdeviren, E. Ye, S.K. Mallapragada, and D.S. Sakaguchi. High throughput characterization of adult stem cells engineered for delivery of therapeutic factors for neuroprotective strategies. J. Visualized Experiments. (in press).
- S.L. Solin, Y. Wang, J. Mauldin, L. Schultz, D.E. Lincow, P.A. Brodskiy, C.A. Jones, J. Syrkin-Nikolau, J.M. Linn, J.J. Essner, J.M. Hostetter, E.M. Whitley, J.D. Cameron, H-H. Chou, A.J. Severin, D.S. Sakaguchi, M. McGrail. (2014) Molecular and cellular characterization of a zebrafish optic pathway tumor line implicates glia-derived progenitors in tumorigenesis. PLoS ONE. (in press).
- Oh, J., Daniels, G.J., Chiou, L.S., Ye, E.-A., Jeong, Y.S. and Sakaguchi, D.S. (2014) Multipotent adult hippocampal progenitor cells maintained as neurospheres favored differentiation toward glial lineages. Biotechnology Journal. 9(7): 921-933.
- A. Sharma, M. Marti, D.S. Sakaguchi, and S.K. Mallapragada (2013) In “Nanomaterials in Tissue Engineering: Characterization, Fabrication and Applications”, Gaharwar, Sant, Hancock and Harding (eds.). Harvard-MIT Division of Health Sciences, published by Woodhead Publishing-Cambridge.
- M. Marti, D.S. Sakaguchi, and S.K. Mallapragada (2012) Neural tissue engineering strategies. In “Biomedical and Health Research. Series, Regenerative Medicine and Cell Therapy” J.F. Stoltz (ed.). IOS Press-Amsterdam
- Howk, C., Levine, H.A., Smiley, M.W., Mallapragada, S.K., Nilsen-Hamilton, M., Oh. J. and Sakaguchi, D.S. (2012) A mathematical model for selective differentiation of neural progenitor cells on micropatterned polymer substrates. Mathematical Biosciences. 238(2): 65-79.
- L.K. Petersen, J. Oh, D.S. Sakaguchi, S.K. Mallapragada, and B. Narasimhan. (2011) Amphiphilic Polyanhydride Films Promote Neural Stem Cell Growth and Adhesion. Tissue Engineering, Part A. 17 (19, 20): 2533-2541.
- M.M. Harper, S. Grozdanic, B. Blits, M. Keuhn D. Zamzow, J. Buss, R. Kardon, D.S. Sakaguchi (2011) Transplantation of BDNF secreting mesenchymal stem cells provides neuroprotection in chronic hypertensive rat eyes. Investigative Ophthalmology and Visual Science. 52(7): 4506-15.
- Ariza, C.A., Fluery, A.T., Toromos, C.J., Petruk, V., Chawla, S., Oh, J., Sakaguchi, D.S., and Mallapragada, S.K. (2010) Altered Neurogenesis, Alignment, and Viability: The influence of an Electric Field on Hippocampal Neural Progenitor Cells. Stem Cell Reviews and Reports. 6(4): 585-600.
- Oh, J., Blong, C.C., McCloskey, M.A., Nilsen-Hamilton, M., and Sakaguchi, D.S. (2010) Astrocyte-derived interleukin-6 promotes specific neuronal differentiation of neural progenitor cells from adult hippocampus. J. Neurosci. Res. 88(13): 2798-2809.
- Grozdanic, S.G., Lazic, T., Harper, M.M., Kardon, R.H., Kuehn, M.H., Lavik, E., Kwon, Y.H., Sakaguchi, D.S. (2010) Exogenous modulation of intrinsic optic nerve neuroprotective activity. Graefes Arch Clin Exp Ophthalmol. 248(8): 1105-1116.
- C.C. Blong, C.-J. Jeon, J.-Y. Yeo, E.-A. Ye, J. Oh, J.M. Callahan, W.D. Law, S. Mallapragada, and D.S. Sakaguchi. (2010) Differentiation and Behavior of Human Neural Progenitor Cells on Micropatterned Substrates and After Transplantation into the Developing Retina. Journal of Neuroscience Research. 88(7): 1445-56.
- Ariza, C.A., McHugh, K.P., White, S.J., Sakaguchi, D.S., and Mallapragada, S.K. (2010) Extracellular Matrix Proteins and Astrocyte-Derived Soluble Factors Influence the Differentiation and Proliferation of Adult Neural Progenitor Cells Journal of Biomedical Materials Research A. 94(3): 816-824.
- M.M. Harper, E.A. Ye, C.C. Blong, M.L. Jacobson and D.S. Sakaguchi. (2010) Integrins contribute to initial morphological development and process outgrowth in adult hippocampal progenitor cells. Journal of Molecular Neuroscience. 40(3): 269-283.
- E. N. Boote Jones, D.S. Sakaguchi, and S.K. Mallapragada. 2009. Development and differentiation of neural stem and progenitor cells on synthetic and biological-based surfaces. In “Biological Interactions on Materials Surfaces: Understanding and Controlling Protein, Cell, and Tissue Responses”, D.A. Puleo and R. Bizios (eds.) Springer Science/Business Media, LLC .
- M.M. Harper, L. Adamson, B. Blits, M.B. Bunge, S.D. Grozdanic, D.S. Sakaguchi. 2009. Brain-derived neurotrophic factor released from engineered mesenchymal stem cells attenuates glutamate- and hydrogen peroxide-mediated death of staurosporine differentiated RGC-5s. Exp. Eye. Res 89:538-548.
- M.M. Harper, E.A. Ye, C.C. Blong, M.L. Jacobson and D.S. Sakaguchi. 2009. Integrins contribute to initial morphological development and process outgrowth in adult hippocampal progenitor cells. Journal of Molecular Neuroscience :In press.
- Tyra Dunn-Thomas, Drena L. Dobbs, Donald S. Sakaguchi, Michael J. Young, Vasant G. Honavar, M. Heather West Greenlee. 2008. Proteomic differentiation between murine retinal and brain-derived progenitor cells. Stem Cells and Development 17(1):119-132.
- Sakaguchi, D.S., Van Hoffelen, S.J., Greenlee, M.H.W., Harper, M.H., and Au, D.. 2008. Cell birth and death in the retina of the Brazilian opossum, Monodelphis domestica. Brain Research 1195C:28-42.
- Ostojic, J., Grozdanic, S.D., Syed, N.A., Hargrove, M.S., Trent, J.T. III, Kuehn, M.H., Kwon, Y.H., Kardon, R.H., and Sakaguchi, D.S. . 2008. Patterns of Distribution of Oxygen Binding Globins, Neuroglobin and Cytoglobin in Human Retina . Archives of Ophthalmology. 126(11):1530-1536.
- Oh, J., Recknor, J.B., Recknor, J.C., Mallapragada, S.K., and Sakaguchi, D.S.. 2008. Soluble factors from neocortical astrocytes enhance neuronal differentiation of neural progenitor cells from adult rat hippocampus on polymer substrates.. Journal of Biomedical Materials Research A. :In press.
- Sakaguchi, D.S., Klassen, H., and Young, M.J. . 2007. Transplantation of neural progenitors to the developing retina. . In “Strategies for Retinal Tissue Repair and Regeneration in Vertebrates: from Fish to Human”. Ed. C. Chiba. :113-137..
- S.D. Grozdanic, A.M. Ast, T. Lazic, Y.H. Kwon, R.H. Kardon, D.M. Betts, I.M. Sonea and D.S. Sakaguchi. 2006. Morphological integration and functional assessment of transplanted neural progenitor cells in healthy and acute ischemic rat eyes. Experimental Eye Research 82(4):597-607.
- Ourenik, J., Ourednik, V., Sakaguchi, D.S. and Nilsen-Hamilton, M. (eds.). 2005. Stem Cell Biology: Development and Plasticity. Annals of the New York Academy of Sciences 1049.
- Klassen, H., Sakaguchi, D.S. and Young, M.J. 2004. Stem Cells and Retinal Repair. Progress in Retinal Eye Research 23: 149-181.