Fumihiko Urano, MD, PhD
Associate Professor of Molecular Medicine
University of Massachusetts Medical School
Faculty page:  http://profiles.umassmed.edu/profiles/ProfileDetails.aspx?From=SE&Person=754
Lab website:  http://www.erstress.com/Welcome.html

Combating Juvenile-Onset Neurodegenerative Diseases

Wolfram syndrome is a rare autosomal recessive disorder characterized by progressive ataxia, blindness, deafness, diabetes mellitus, diabetes insipidus, and death from neurodegeneration in the third or fourth decade. Currently, no treatment can slow the progression of the disease, thus raising the urgency for developing new therapeutic strategies to combat Wolfram syndrome. Our group has established an international registry and tissue bank of patients with Wolfram syndrome to understand the pathogenesis and natural course of this disorder. We are also producing inducible pluripotent stem cells (iPS cells) to understand the disease and use these cells for treatment. We discovered the causative gene, and developed cell and animal models of Wolfram syndrome that can be used to identify novel therapeutic strategies. Our goal is to discover drugs to treat the disease, a lethal, monogenic form of neurodegeneration and diabetes. Therapeutic modalities identified in a monogenic disease will serve as proof-of-principle for extending such treatments to patients with common genetic and environmentally complex forms other neurodegenerative disorders such as ALS.

List of Key Papers

Fonseca, S.G., Fukuma, M., Lipson, K., Nguyen, L.X., Allen, J.R., Oka, Y., and Urano F. WFS1 is a novel component of the unfolded protein response and maintains ER homeostasis in pancreatic β cells. J Biol Chem, 280(47): 39609-615, 2005.

Ishigaki, S., Niwa, J., Yamada, S., Takahashi, M., Ito, T., Sone, J., Doyu, M., Urano, F., and Sobue, G. Dorfin-CHIP chimeric proteins potently ubiquitylate and degrade familial ALS-related mutant SOD1 proteins and reduce their cellular toxicity. Neurobiology of Disease, 25(2): 231-41, 2007.

Ishigaki, S., Fonseca, S.G., Oslowski, C.M, Jurczyk, A., Shearstone, J.R., Zhu, L.J., Permutt, M.A., Greiner, D.L., Bortell, R., and Urano, F. AATF mediates anti-apoptotic effect of the unfolded protein response through transcriptional regulation of AKT1. Cell Death Differ, 17(5):774-86, 2010

Fonseca, S.G., Ishigaki, S., Oslowski, C.M, Lu, S., Lipson, K.L., Ghosh, R., Hayashi, E., Ishihara, H., Oka, Y., Permutt, M.A., and Urano, F. Wolfram syndrome 1 gene negatively regulates ER stress signaling in rodent and human cells. J Clin Invest, 120(3): 744-55, 2010.

Oslowski, C.M. and Urano, F. The binary switch that controls the life and death decisions of ER stressed beta cells. Curr Opin Cell Biol, [Epub Ahed of Print], 2010.

Oslowski, C.M. and Urano, F. Measuring ER stress and the unfolded protein response using mammalian tissue culture system. Methods in Enzymology, 490:71-92, 2011.


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