School of Medicine

Dr Tomoko Iwata

Dr Tomoko Iwata
  • Senior Lecturer (Clinical Specialties)
  • Associate Academic (Institute of Cancer Sciences)

telephone: 01413303507
email: Tomoko.Iwata@glasgow.ac.uk


Our research interest is to understand the mechanism of forebrain development via signalling through Fibroblast Growth Factors (FGFs) and the array of disease phenotypes caused by mutations in its tyrosine kinase receptor, FGFR3, including cancer. Growth factors are a classic class of molecules that controls G1 phase, however, their role has not been well characterised in the in vivo context.

We have previously generated conditional knock-in mice with kinase domain mutations in FGFR3, associated with two neonatal lethal dwarfisms of Achondroplasia type. We have established that our mouse models show characteristics that closely resemble those seen in human patients. The mutant mice displayed an enlarged brain with an increase in cortical thickness, uncovering the previously unknown role of FGFR3 in brain development. We are currently investigating the mechanism of cell cycle control in progenitors of the cerebral cortex. We have also launched on a pilot MRI study of FGFR3 mutant mice brains, in order to systematically assess its relevance in cortical and hippocampal malformations observed in human patients. Postnatal expression of FGFR3 in astroglial lineage may also indicate its potential invovlment in regulation of postnatal neural stem/progenitor cells.

In addition to developmental defects, FGFR3 mutations are also involved in various forms of cancer. Expression and the effects of FGFR3 mutations in bladder epithelia are currently investigated in mouse models.

Jump to: 2012 | 2011 | 2010 | 2009 | 2007 | 2006 | 2005 | 2004 | 2001 | 2000 | 1999
Number of items: 15.

2012

Ahmad, I., Iwata, T. , and Leung, H.Y. (2012) Mechanisms of FGFR-mediated carcinogenesis. Biochimica et Biophysica Acta-Molecular Cell Research, 1823 (4). pp. 850-860. ISSN 0167-4889 (doi:10.1016/j.bbamcr.2012.01.004)

2011

Ahmad, I., Singh, L.B. , Foth, M., Morris, C.-A., Taketo, M.M., Wu, X.-R., Leung, H.Y. , Sansom, O.J. , and Iwata, T. (2011) K-Ras and β-catenin mutations cooperate with Fgfr3 mutations in mice to promote tumorigenesis in the skin and lung, but not in the bladder. Disease Models & Mechanisms, 4 (4). pp. 548-555. ISSN 1754-8403 (doi:10.1242/dmm.006874)

Moldrich, R.X. et al. (2011) Fgfr3 regulates development of the caudal telencephalon. Developmental Dynamics, 240 (6). pp. 1586-1599. ISSN 1058-8388 (doi:10.1002/dvdy.22636)

2010

Pellicano, F., Thomson, R.E. , Inman, G.I. , and Iwata, T. (2010) Regulation of cell proliferation and apoptosis in neuroblastoma cells by ccp1, a FGF2 downstream gene. BMC Cancer, 10 (1). p. 657. ISSN 1471-2407 (doi:10.1186/1471-2407-10-657)

2009

Iwata, T, and Hevner, RF (2009) Fibroblast growth factor signaling in development of the cerebral cortex. Development Growth and Differentiation, 51 (3). pp. 299-323.

Thomson, R., Kind, P.C., Graham, N.A., Etherson, M.L., Kennedy, J. , Fernandes, A.C., Marques, C.S., Hevner, R.F., and Iwata, T. (2009) Fgf receptor 3 activation promotes selective growth and expansion of occipitotemporal cortex. Neural Development, 4 (4). ISSN 1749-8104 (doi:10.1186/1749-8104-4-4)

2007

Thomson, RE, Pellicano, F, and Iwata, T (2007) Fibroblast growth factor receptor 3 kinase domain mutation increases cortical progenitor proliferation via mitogen-activated protein kinase activation. Journal of Neurochemistry, 100 . pp. 1565-1578. (doi:10.1111/j.1471-4159.2006.04285.x)

2006

Ambrosino, C, Iwata, T , Scafoglio, C, Mallardo, M, Klein, R, and Nebreda, AR (2006) TEF-1 and C/EBPbeta are major p38alpha MAPK-regulated transcription factors in proliferating cardiomyocytes. Biochemical Journal, 396 (1). pp. 163-172. ISSN 0264-6021

Pellicano, F, Inglis-Broadgate, SL, Pante, G, Ansorge, W, and Iwata, T (2006) Expression of coiled-coil protein 1, a novel gene downstream of FGF2, in the developing brain. Gene Expression Patterns, 6 . pp. 285-293. (doi:10.1016/j.modgep.2005.07.004)

2005

Inglis-Broadgate, SL, Thomson, RE, Pellicano, F, Tartaglia, MA, Pontikis, CC, Cooper, JD, and Iwata, T (2005) FGFR3 regulates brain size by controlling progenitor cell proliferation and apoptosis during embryonic development. Developmental Biology, 279 . pp. 73-85. (doi:10.1016/j.ydbio.2004.11.035)

Pante, G, Thompson, J, Lamballe, F, Iwata, T , Ferby, I, Barr, FA, Davies, AM, Maina, F, and Klein, R (2005) Mitogen-inducible gene 6 is an endogenous inhibitor of HGF/Met-induced cell migration and neurite growth. Journal of Cell Biology, 171 . pp. 337-348.

2004

Cho, JY, Guo, C, Torello, M, Lunstrum, GP, Iwata, T , Deng, C, and Horton, WA (2004) Defective lysosomal targeting of activated fibroblast growth factor receptor 3 in achondroplasia. Proc Natl Acad Sci U S A, 101 (2). pp. 609-614.

2001

Iwata, T, Li, CL, Deng, CX, and Francomano, CA (2001) Highly activated Fgfr3 with the K644M mutation causes prolonged survival in severe dwarf mice. Human Molecular Genetics, 10 (12). pp. 1255-1264. ISSN 0964-6906

2000

Iwata, T., Chen, L., Li, C., Ovchinnikov, D.A., Behringer, R.R., Francomano, C.A., and Deng, C.X. (2000) A neonatal lethal mutation in FGFR3 uncouples proliferation and differentiation of growth plate chondrocytes in embryos. Human Molecular Genetics, 9 (11). pp. 1603-13. ISSN 0964-6906

1999

Li, C., Chen, L., Iwata, T. , Kitagawa, M., Fu, X.Y., and Deng, C.X. (1999) A Lys644Glu substitution in fibroblast growth factor receptor 3 (FGFR3) causes dwarfism in mice by activation of STATs and ink4 cell cycle inhibitors. Human Molecular Genetics, 8 (1). pp. 35-44. ISSN 0964-6906

This list was generated on Sat May 26 13:05:50 2012 BST.
  • Cortical Development Meeting (Crete) and ISDB/JSDB [International Society of Developmental Biologists/Japanese Society of Developmental Biologists] Meeting (Japan)
    Scottish Stem Cell Network
    2008 - 2008
     
  • A pilot analysis of the brain structure of fibroblast growth factor receptor 3 mutant mice by magnetic resonance imaging
    Neurosciences Foundation
    2007 - 2008
     
  • Control of cell cycle & apoptosis in cortical progenitors by Fgf receptor 3
    BBSRC
    2004 - 2007
     

Research Fellowship

  • 1996 - 2000: Fogarty Visiting Fellow - National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH), Maryland, USA