Dr. Sakaguchi, Morrill 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.
- Bierlein del la Rosa, M., Sharma, A.D., Mallapragada, S.K., and Sakaguchi, D.S. 2017. Transdifferentiation of BDNF-hypersecreting MSCs significantly enhances BDNF secretion and Schwann cell marker proteins. J Biosci Bioeng. 124(5), 572-582. doi: 10.1016/j.jbiosc.2017.05.014. PMID: 28694020.
- D.S. Sakaguchi. 2017. Regenerative and Repair Strategies for the Central Nervous System. In “Neuroimmune Pharmacology, Second Edition”. T. Ikezu and H. Gendelman (eds.). Springer.
- Sharma, A.D., Weiderin, J., Uz, M. Ciborowski, P., Mallapragada, S.K., Gendelman, H. E., and Sakaguchi, D.S. (2017) Proteomic analysis of mesenchymal to Schwann cell transdifferentiation. J. Proteomics. 195: 93-101. doi: 10.1016/j.prot.2017.06.011. PMID: 28629798.
- Mammadova, N., Ghaisas, S., Zenitsky, G., Sakaguchi, D.S., Kanthasamy, A.G., Greenlee, J.J. and West Greenlee, M.H. 2017. Lasting retinal injury in a mouse model of blast-induced trauma. Am J Path. 187: 1459-1472. PMID: 28606756. DOI: 10.1016/j.ajpath.2017.03.005
- Uz, M., Büyüköz, M., Sharma, A.D., Sakaguchi, D.S., Altinkaya, S.A., Mallapragada, S.K. Gelatin-based 3D conduits for transdifferentiation of mesenchymal stem cells into Schwann cell-like phenotypes. Acta Biomater. 2017 53:293-306. doi: 10.1016/j.actbio.2017.02.018. PMID: 28213098
- Das, S.R., Uz, M., Ding, S., Lentner, M.T., Hondred, J.A., Cargill, A.A., Sakaguchi, D.S., Mallapragada, S.K., Claussen, J.C. Electrical Differentiation of Mesenchymal Stem Cells into Schwann Cell-Like Phenotypes using Inkjet Printed Graphene Circuits. Adv Healthc Mater. 2017, 6(7) doi: 10.1002/adhm.201601087.
- Schultz, L.E., Solin, S.L., Lovan, J.M., Lawrence, C.A., Syrkin-Nikolau, J., Lincow, D.E., Sakaguchi, D.S., and McGrail, M. VEGFA and Leptin expression associated with ectopic proliferation and retinal dysplasia in zebrafish optic pathway tumors. Zebrafish. 2017 doi: 10.1089/zeb.2016.1366. PMID: 28192065
- E.J. Sandquist, M. Uz, A.D. Sharma, B.B. Patel, S.K. Mallapragada and D.S. Sakaguchi (2016). Stem cells, bioengineering and 3-D scaffolds for nervous system repair and regeneration. In “Neural Engineering: from Advanced Biomaterials to 3D Fabrication Techniques”, L.G. Zhang and D. Kaplan (eds.). Springer.
- Ye, E., Chawla, S.S., Khan, M.Z., and Sakaguchi, D.S. Bone marrow-derived mesenchymal stem cells (MSCs) stimulate neurite outgrowth from differentiating adult hippocampal progenitor cells. Journal of Stem Cell Biology and Research. 2016. 3:3.
- Uz, M., Sharma, A.D., Adhikari, P., Sakaguchi, D.S., Mallapragada, S.K. Development of Multifunctional Films for Peripheral Nerve Regeneration. Acta Biomater. 2016 Sep 29. pii: S1742-7061(16)30512-8. doi: 10.1016/j.actbio.2016.09.039. PMID: 27693689
- Sharifi, F., Patel, B.B., Dzuilko, A.K., Montazami, R., Sakaguchi, D.S., Hashemi, N. Microfluidic Spun Poly (ε-caprolactone) Microfibrous Scaffolds to Navigate Neural Stem Cells. Biomacromolecules. 2016, 17(10):3287-3297. DOI: 10.1021/acs.biomac.6b01028.
- Sharma, A.D., Zbarska, S., Petersen, E.M., Marti, M.E., Mallapragada, S.K., Sakaguchi, D.S. Oriented growth and transdifferentiation of mesenchymal stem cells towards a Schwann cell fate on micropatterned substrates. J Biosci Bioeng. 2015 Sep 11. pii: S1389-1723(15)00291-1. doi: 10.1016/j.jbiosc.2015.07.006. [Epub ahead of print] PubMed PMID: 26371993.
- Mallapragada, S.K., Brenza, T.M., McMillan, J.M., Narasimhan, B., Sakaguchi, D.S., Sharma, A.D., Zbarska, S., Gendelman, H.E. Enabling nanomaterial, nanofabrication and cellular technologies for nanoneuromedicines. Nanomedicine. 2015 Apr;11(3):715-29. doi: 10.1016/j.nano.2014.12.013. Epub 2015 Jan 31. Review. PubMed PMID: 25652894.
- Kumar, V., Bigelow, T.A., Mullin, K., Sakaguchi, D.S. Correlation of Hemorrhage Near Developing Opossum Skull With Pulsed Ultrasound Exposure Parameters. J Ultrasound Med. 2015 Aug;34(8):1351-61. doi: 10.7863/ultra.34.8.1351. PubMed PMID: 26206821.
- Sharma, A.D., Brodskiy, P.A., Petersen, E.M., Dagdeviren, M., Ye, E.A., Mallapragada, S.K., Sakaguchi D.S. High throughput characterization of adult stem cells engineered for delivery of therapeutic factors for neuroprotective strategies. J Vis Exp. 2015 Jan 4;(95):e52242. doi: 10.3791/52242. PubMed PMID: 25590859.
- 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.