Assistan Professor ： Takako Sasaki Research Projects ： Functional analyses and structure-function relationships of extracellular matrix proteins We analyze structure-function relationships of various extracellular matrix proteins.In the past, we have analyzed particularly those derived from basement membranes (laminins, nidogens, perlecan, BM-40/SPARC, collagen XV and collagen XVIII) using recombinant technique and produce various domains of these proteins in eukaryotic cells. We have characterized their binding properties for protein ligands and cellular receptors. Furthermore, we have mapped the binding epitopes by site-directed mutagenesis. Currently we focus on fibulin family and analyze their functions in vitro and in vivo . 1) Surmann-Schmitt C, Sasaki T, Hattori T, Eitzinger N, Schett G, von der Mark K and Stock M (2012) The Wnt antagonist Wif-1 interacts with CTGF and inhibits CTGF activity. J. Cell Physiol., 227, 2207-2216. 2) Moriya K, Bae E, Honda K, Sakai K, Sakaguchi T, Tsujimoto I, Kamisoyama H, Keene DR, Sasaki T and Sakai T (2011) A fibronectin-independent mechanism of collagenfibrillogenesis in adult liver remodeling. Gastroenterology, 140, 1653-1663. 3) Sasaki T, Takagi J, Giudici C, Yamada Y, Arikawa-Hirasawa E, Deutzmann R, Timpl R, Sonnenberg A, Bächinger HP, Tonge D (2010) Laminin-121 – recombinant expression and interactions with integrins. Matrix Biol., 29, 484-493. 4) McCulloch DR, Nelson CM, Dixon LJ, Wylie JD, Lindner V, Sasaki T, Cooley MA,  Argraves WS, Apte SS (2009) ADAMTS metalloproteases generate active versican fragments that regulate interdigital web regression. Dev. Cell, 17, 687-698. 5) Hohenester E, Sasaki T, Giudici C, Farndale RW and Bächinger HP (2008)  Structural basis of sequence-specific collagen recognition by SPARC.Proc. Natl. Acad. Sci, USA, 105, 18273-18277. 6) Giudici C, Raynal N, Wiedemann H, Cabral WA, Marini JC, Timpl R, Bächinger HP, Farndale RW, Sasaki T and Tenni R (2008) Mapping of SPARC/BM-40/osteonectin-binding sites on fibrillar collagens. J. Biol. Chem., 283, 19551-19560. 7) Kobayashi N, Kostka G, Garbe, JHO, Keene DR, Bächinger HP., Hanisch F-G, Markova D, Tsuda T, Timpl R, Chu M-L and Sasaki T (2007)  A comparative analysis of the fibulin protein family: Biochemical characterization, binding interactions and tissue localization. J. Biol. Chem., 282, 11805-11816. 8) Sasaki T, Knyazev PG, Clout NJ, Cheburkin Y, Göhring W, Ullrich A, Timpl R and Hohenester E (2006) Structural basis for Gas6-Axl signalling.EMBO J, 25, 80-87. 9) Sasaki T, Fässler R, and Hohenester E (2004). Laminin: the crux of basement membrane assembly. J. Cell Biol., 164:959-963. Minireview 10) Timpl R, Sasaki T, Kostka G and Chu M-L (2003). Fibulins: a versatile family of extracellular matrix proteins. Nat Rev Mol Cell Biol. 4, 479-489. Review.