Our research focus is to develop stem cell therapies for neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and ALS.
We reported that human fetal neural stem cells transplanted into 24-month-old rats developed into neural cells and significantly improved the cognitive function of the animals. However, ethical and technical issues put off the clinical use of fetal or embryonic stem cell. Recently we succeeded to produce neural cells form adult human mesenchimal stem cells after modification of DNA methylation. Currently, we are investigating genes, which regulate stemness to convert committed cells into pluripotent cells. We also one-step further to extend this autologous cell therapy concept by a small molecule compound. Peripheral administrations of this compund not only dramatically (7 fold) increases endogenous neural stem cell but also neurogenesis in the aged rats.
Investigation of stem cell biology also give us a clue for cause of disease. We found reelin, which expression is known to be reduced in schizophrenia and autism, and ?-amyloid precursor protein (APP), which produces amyloid ? depositions in Alzheimer’s disease, are involved in stem cell migration and differentiation using knockout and/or transgenic mice. Thus these factors may play an important role not only in neuroplasticity in the normal condition, but also in a deficit of adult neurogenesis under pathological conditions. Thus we are investigating novel therapeutic strategies for this disease, including modifications of stem cell and regulation of these factors.
Using all these advanced stem cell technologies, we may be able to change therapeutic strategies for neurodegenerative diseases form delaying progress of the diseases or symptomatic treatments to the cure near future. Our researches are supported by NIH (R01 AG 23472 and R01AG20011) and Alzheimer’s Association (IIRG-03-5577).
1. Alvarez A, Hossain M, Dantuma E, Merchant S, and Sugaya K. Nanog overexpression allows human mesenchymal stem cells to differentiate into neural cells. 2010 Neuroscience & Medicine in press
2. Merchant S, Dantuma E, and Sugaya K: A heterocyclic pyrrolopyrimidine compound as a possible candidate for topical application to induce hair restoration. 2010 Advanced Studies in Biology; 2(2): 63-71.
3. Field M, Bushnev S, Sugaya K.: Embryonic stem cell markers distinguishing cancer stem cells from normal human neuronal stem cell populations in malignant glioma patients. 2010 Clinical Neurosurgery in press
4. Kwak YD, Dantuma E, Merchant S, Bushnev S, Sugaya K: Amyloid-β Precursor Protein Induces Glial Differentiation of Neural Progenitor Cells by Activation of the IL-6/gp130 Signaling Pathway. 2010 Neurotoxicity Research. in press
5. Sugaya, K.: Stem Cell Biology in the Study of Pathological Conditions. 2010 Neurodegenerative Diseases; 7(1-3): 84-87.
6. Chigurupati S, Venkataraman R, Barrera D, Naganathan A, Madan M, Paul L, Pattisapu JV, Kyriazis GA, Sugaya K, Bushnev S, Lathia JD, Rich JN, and Chan SL: Receptor channel TRPC6 is a key mediator of Notch-driven glioblastoma growth and invasiveness. 2010 Cancer Research; 70(1): 418—27.
7. Field, Melvin M.D.; Bushnev, Sergey M.D.; Alvarez, Angel A. B.S.; Avgeropoulos, Nicholas M.D.; Sugaya, Kimi Ph.D, Markers Distinguishing Cancer Stem Cells from Normal Human Neuronal Stem Cell Populations in Malignant Glioma Patients,Neurosurgery: August 2009 65(2) 426
8. Biener G, Vrotsos E, Sugaya K, Dogariu A. Optical torques guiding cell motilityOpt Express. 2009 Jun 8;17(12):9724-32
9. Vrotsos EG, Kolattukudy PE, Sugaya K. MCP-1 involvement in glial differentiation of neuroprogenitor cells through APP signaling. Brain Res Bull. 2009 Apr 29;79(2):97-103.
10. Vrotsos EG, Sugaya K. MCP-1-induced migration of NT2 neuroprogenitor cells involving APP signaling. Cell Mol Neurobiol. 2009 May;29(3):373-81.
11. Sugaya K, Merchant S. How to approach Alzheimer’s disease therapy using stem cell technologies. J Alzheimers Dis. 2008 Oct;15(2):241-54. Review.
12. Keilani S, Sugaya K. Reelin induces a radial glial phenotype in human neural progenitor cells by activation of Notch-1. BMC Dev Biol. 2008 Jul 1;8:69-75.
13. Liu D, Hua KA, Sugaya K., A generic framework for internet-based interactive applications of high-resolution 3-D medical image data. IEEE Trans Inf Technol Biomed. 2008 Sep;12(5):618-26.
14. Sugaya K. Mechanism of glial differentiation of neural progenitor cells by amyloid precursor protein. Neurodegener Dis. 2008;5(3-4)
15. Marutle A, Ohmitsu M, Nilbratt M, Greig NH, Nordberg A, Sugaya K. Modulation of human neural stem cell differentiation in Alzheimer (APP23) transgenic mice by phenserine. Proc Natl Acad Sci U S A. 2007 Jul 24;104(30):12506-11
16. Sugaya K., Y.D. Kwak, O. Ohmitsu, A. Marutle, N.H. Greig and E. Choumrina Practical Issues in Stem Cell Therapy for Alzheimer’s Disease. Current Alzheimer Research 2007; 4(4):370-377
17. Pulido JS, Sugaya I, Comstock J, Sugaya K. Reelin expression is upregulated following ocular tissue injury. Graefes Arch Clin Exp Ophthalmol. 2007 Jun;245(6):889-893