Home
Department
Faculty
Staff
Graduate Program
Undergraduate Program
Computing
Science Resources
School of Medicine
Stony Brook
PHM Logo
Ken-Ichi Takemaru, Ph.D. - Assistant Professor
Ken-Ichi Takemaru, Ph.D.

Assistant Professor
Pharmacological Sciences
Genetics & MCB Programs

Ph.D., Graduate University for Advanced Studies, Japan
Postdoctoral, University of Washington
Dept. of Pharmacology BST 7-182
Stony Brook, NY 11794-8651
Phone: (631) 444-7976
Fax: (631) 444-3218
E-mail: takemaru@pharm.stonybrook.edu

 

Wnt Signaling in Development and Disease

Intracellular signaling by the Wnt family of secreted cysteine-rich glycoproteins plays critical roles in normal embryonic development and adult homeostasis. This pathway is highly conserved among the animal kingdom. Importantly, dysregulation of Wnt signaling has been linked to a range of human diseases. For instance, the best understood Wnt/β-catenin pathway is aberrantly activated in greater than 70 % of colorectal cancers and to a lesser extent in other tumor types, promoting cancer cell proliferation, survival and migration. More recently, this signaling cascade has emerged as a crucial regulator of stem cells. Our laboratory investigates the function of Wnt/β-catenin signaling in development and disease. More specific projects are outlined below.

wnt_pathway

 






 



 




Research Overview

We previously reported a β-catenin-associated antagonist Chibby (Cby). Cby is a 14.5-kDa nuclear protein, and evolutionarily conserved from fly to human. Cby physically interacts with the C-terminal activation domain of β-catenin and represses β-catenin-mediated transcriptional activation. Mechanistically, Cby competes with Tcf/Lef transcription factors to bind to β-catenin. Depletion of Drosophila Cby by RNAi results in segment polarity defects that mimick the gain-of-function phenotype of a Drosophila Wnt homolog wingless (wg), highlighting the biological importance of Cby’s function. Recently, we found that Cby promotes adipocyte and cardiomyocyte differentiation of pluripotent stem cells through inhibition of β-catenin signaling. Our current projects include: 1) Isolation and characterization of Cby-interacting proteins; 2) Characterization of Cby-knockout mice; 3) Involvement of Cby in human cancer.

cby_adipocyte

cby_lung_2























Research Opportunities in the Takemaru Lab

There are research positions available in the lab. We are always looking for motivated and talented undergraduate and graduate students, as well as postdoctoral fellows. We utilize a range of state-of-the-art approaches to study various aspects of Wnt signaling. For more information, please inquire here.

2008
Voronina, V.A., Takemaru, K.-I.*, Grubb, B.R. Treuting, P., Hajjar, A.M., Adams, A., Love, D., Wilson, C.B. & Moon, R.T.* (2008)
Inactivaton of Chibby affects function of motile airway cilia.
In revision. *Co-correspondence.

Cohen, J.C., Larson, J.E., Killeen, E., Love, D. & Takemaru, K.-I. (2008)
CFTR and Wnt/β-catenin signaling in lung development.
BMC Dev. Biol., In press.

Li, F.-Q., Mofunanya, A., Harris, K. & Takemaru, K.-I. (2008)
Chibby cooperates with 14-3-3 to regulate β-catenin subcellular distribution and signaling activity.
J. Cell Biol., 181:1141-1154.

Takemaru, K.-I., Ohmitsu, M. & Li, F.-Q. (2008)
An oncogenic hub: β-catenin as a molecular target for cancer therapeutics.
Handb. Exp. Pharmacol., 186:261-284.

Xing, Y., Takemaru, K.-I., Liu, J., Berndt, J.D., Zheng, J., Moon, R.T. & Xu, W. (2008)
Crystal structure of a full-length β-catenin.
Structure, 16:478-487.

  Smile Preview by Gottardi, C.J. & Peifer M. (2008)
       Terminal regions of β-catenin come into view.
       Structure, 16:336-338.

2007
Li, F.-Q., Singh, A.M., Mofunanya, A, Love, D., Terada, N., Moon, R.T. & Takemaru, K.-I. (2007)
Chibby promotes adipocyte differentiation through inhibition of β-catenin signaling.
Mol. Cell. Biol., 27:4347-4354.

Singh, A.M., Li, F.-Q., Hamazaki, T., Takemaru, K.-I. & Terada, N. (2007)
Chibby, an antagonist of the Wnt/β-catenin pathway, facilitates cardiomyocyte differentiation of murine embryonic stem cells.
Circulation, 115:617-626.

2006
Schuierer, M.M., Graf, E., Takemaru, K.-I., Dietmaier, W. & Bosserhoff, A.K. (2006)
Reduced expression of β-catenin inhibitor Chibby in colon carcinoma cell lines.
World J. Gastroenterol., 12:1529-1535.

Takemaru, K.-I. (2006)
β-Catenin.
AfCS-Nature Molecule Pages, doi:10.1038/mp.a000506.01.

2004
Li, F.-Q., Person, R.E., Takemaru, K.-I., Williams, K., Meade-White, K., Ozsahin, A.H., Gngr, T., Moon, R.T. & Horwitz, M. (2004)
Lymphoid enhancer factor-1 links two hereditary leukemia syndromes through core-binding factor α regulation of ELA2.
J. Biol. Chem., 279:2873-2884.

2003
Mak, B.C., Takemaru, K.-I., Kenerson, H.L., Moon, R.T. & Yeung, R.S. (2003)
The tuberin-hamartin complex negatively regulates β-catenin signaling activity.
J. Biol. Chem., 278: 5947-5951.

Takemaru, K.-I., Yamaguchi, S., Lee, Y.S., Zhang, Y., Carthew, R.W. & Moon, R.T. (2003)
Chibby, a nuclear β-catenin-associated antagonist of the Wnt/Wingless pathway.
Nature, 422:905-909.

  Smile News and Views by Greaves, S. (2003)
       Small changes in Wnt signalling.
       Nat. Cell Biol., 5: 387.

2002
Cheyette, B.N., Waxman, J.S., Miller, J.R., Takemaru, K.-I., Sheldahl, L.C., Khlebtsova, N., Fox, E.P., Earnest, T. & Moon, R.T. (2002)
Dapper, a Dishevelled-associated antagonist of β-catenin and JNK signaling, is required for notochord formation.
Dev. Cell, 2:449-461.

2000
Takemaru, K.-I. & Moon, R.T. (2000)
The transcriptional coactivator CBP interacts with β-catenin to activate gene expression.
J. Cell. Biol., 149:249-254.

D'Amico, M., Hulit, J., Amanatullah, D.F., Zafonte, B.T., Albanese, C., Bouzahzah, B., Fu, M., Augenlicht, L.H., Donehower, L.A., Takemaru, K.-I., Moon, R.T., Davis, R., Lisanti, M.P., Shtutman, M., Zhurinsky, J., Ben-Ze'ev, A., Troussard, A.A., Dedhar, S. & Pestell, R.G. (2000)
The integrin-linked kinase regulates the cyclin D1 gene through glycogen synthase kinase 3β and cAMP-responsive element-binding protein-dependent pathways.
J. Biol. Chem., 275:32649-32657.

1999
Song, K.*, Takemaru, K.-I.* & Moon, R.T. (1999)
A role for xGCNF in midbrain-hindbrain patterning in Xenopus laevis.
Dev. Biol., 213:170-179. *Contributed equally.

McGrew, L.L.*, Takemaru, K.-I.*, Bates, R. & Moon, R.T. (1999)
Direct regulation of the Xenopus engrailed-2 promoter by the Wnt signaling pathway, and a molecular screen for Wnt-responsive genes, confirm a role for Wnt signaling during neural patterning in Xenopus.
Mech. Dev., 87:21-32. *Contributed equally.

Last updated: June 19, 2008.