Email: hiroshi.tsuda [at] mcgill.ca (Hiroshi Tsuda)
Recent Publications: PubMed
Academic Affiliations: Neurology and Neurosurgery
Research Groups: Rare Neurological Diseases, Neurodegenerative Disorders
Dr. Tsuda's research aims to determine the function of genes relevant to major neurodegenerative disorders. His laboratory uses powerful genetic techniques developed for Drosophila, and applies the findings to mouse studies. Dr. Tsuda believes that dissecting pathways using flies and mice is a productive approach in analyzing resultant cellular phenotypes and in uncovering the molecular pathways that underlie amyotrophic lateral sclerosis, Parkinson's Disease, Alzheimer's Disease and other devastating neurological diseases.
Dr. Tsuda's combined analysis of flies and mice has proved valuable in understanding the pathology of neurodegeneration. He has explored the mechanisms underlying Spinocerebellar Ataxia type 1 (SCA1) as well as ALS. In both diseases, he revealed novel neurobiological pathways and pathological defects that led to aberrant phenotypes. His findings have shed light on general neurodegenerative mechanisms, opening possible routes for developing new treatments.
In a significant development, Dr. Tsuda's laboratory has introduced a fly model that carries a mutant ALS protein. This model shows many pathological features common to sporadic and familial forms of ALS. His laboratory's Drosophila studies have successfully uncovered several novel signaling pathways that could be relevant for core ALS pathology. The laboratory has established, moreover, a mouse model carrying the ALS mutation. This mouse model will be useful in preclinical trials for ALS-targeted therapies. As a result, Dr. Tsuda's laboratory is in an excellent position to expand our understanding of ALS pathogenesis and to contribute to the development of more effective therapies for ALS and other deadly neurological diseases.
Barrette, A.M., Lin, Y.Q., Pradhan, S., Neely, G.G., Bellen, H.J., Tsuda, H.*(2013)
Amyotrophic Lateral Sclerosis 8 protein, VAP, is required for ER protein quality control.
Human Molecular Genetics (in press)
Barrette, A.M., Maira M., Tsuda, H.* (2013)
A Secreted Ligand for Growth Cone Receptors, VAP Mediates the Cellular Pathological Defects in ALS. In R. J. Cauchi (Ed.), Drosophila melanogaster Models of Motor Neuron Disease (pp. 35-56). N.Y.: Nova Biomedical
Yang, Z., Huh, S.U., Drennan M., Kathuria, H., Martinez, J. S., Tsuda, H., Hall, C. M., Mark C. Hall, Clemens, J.C. (2012)
Drosophila Vap-33-1 is Required for Axonal Localization of Dscam Isoforms.
Journal of Neuroscience, Nov 28, 2012 • 32(48):17241–17250.
(Highlighted in preview in Journal of Neuroscience)
Han, S.M., Tsuda, H., Yang, Y., Vibbert,J., Tong, C., Cottee, P, Haueter, C., Prasain, J., Bellen, H.J., Miller, M.A. (2012). Secreted VAPB/ALS8 Major Sperm Protein Domains Modulate Mitochondrial Localization and Morphology via Growth Cone Guidance Receptors.
Developmental Cell, Feb 14;22(2):348-62.
(Highlighted on the cover and preview in Developmental Cell)
Mitne-Neto, M., Machado-Costac, M., Marchetto, M.C.., Bengtson, M.H., Joazeiro, C.A., Tsuda, H., Hugo, J. Bellenf, Helga A. C., Silva H.C. , Oliveira A.S., Muotri A. R., Zatz M.(2011)
Downregulation of VAPB expression in motor neurons derived from induced pluripotent stem-cells of ALS8 patients.
Molecular Human Genetics, Sep 15;20(18):3642-52.
Bellen, H.J., Tong, C., Tsuda, H. (2010).
100 years of Drosophila research and its impact on vertebrate neuroscience: a history lesson for the future
Nature Review Neuroscience, Apr 9;11(7):514-522.
Tsuda, H., Han, S.M., Yang, Y., Tong, C., Lin, Y.Q., Mohan, K., Haueter, C., Zoghbi, A., Harati, Y., Kwan, J., Miller, M.A., Bellen, H.J. (2008). The Amyotrophic Lateral Sclerosis 8 protein VAPB is cleaved, secreted, and acts as a ligand for Eph receptors.
Cell, Jun 13, 133:963-977
(Highlighted on the cover and preview in Cell and rated as “Exceptional” by Faculty of 1000)
Tsuda, H., Jafar-Nejad, H., Patel, A.J., Sun, Y., Chen, H.K., Rose, M.F., Venken, K.J., Botas, J., Orr, H.T., Bellen, H.J., Zoghbi, H.Y. (2005). The AXH domain of Ataxin-1 mediates neurodegeneration through its interaction with Gfi-1/Senseless proteins.
Cell, Aug 26; 122:633-644.
(Selected in the News and View section of Nature Neuroscience 2005 Nov; 8: 1422-1424)