Faculty / Research

Ken-Ichi Takemaru, Ph.D.

Associate Professor 


Ph.D., Graduate University for Advanced Studies, Japan

Postdoctoral, University of Washington

(631) 444-7976  ken-ichi.takemaru@stonybrook.edu
Cell Signaling and Ciliogenesis in Mammalian Development, Health and Disease

Wnt Signaling in Development and Disease

Intracellular signaling by the Wnt family of secreted cysteine-rich glycoproteins plays critical roles in embryonic development and adult homeostasis. This pathway is highly conserved among the animal kingdom. Importantly, perturbations of Wnt signaling have been linked to a range of human diseases. For instance, the best understood canonical 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 signaling in the context of development and disease.

Chibby Family Members and Ciliogenesis

Cilia are ancient microtubule-based organelles that protrude from the apical cell surface to perform diverse biological functions, ranging from fluid movement to intracellular signaling. Dysfunctional cilia have been linked to various diseases, collectively known as ciliopathy. We previously reported a β-catenin-associated antagonist Chibby (Cby). Cby is a conserved shuttling protein that blocks transcriptional activation by β-catenin, a key coactivator downstream of canonical Wnt signaling. In our efforts to investigate the physiological function of Cby using Cby-knockout (Cby-/-) mice, we found that these mice suffer from chronic respiratory infections due to a complete absence of mucociliary transport activity. Our studies further uncovered that ciliated cells in the nasal and lung epithelia of Cby-/- mice are poorly differentiated characterized by markedly fewer ciliary projections. Consistent with this phenotype, endogenous Cby protein is highly enriched at the base of cilia, suggesting that Cby plays an essential role in proper formation/function of cilia. In mammals, there are three Cby homologues. Our current research is directed at understanding roles of Cby family members and Wnt/b-catenin signaling in ciliogenesis and ciliated cell differentiation.

Selected Publications

Siller, S.S., Burke, M.C., Li, F.-Q. & Takemaru, K.-I. (2015)
Chibby functions to preserve normal ciliary morphology through the regulation of intraflagellar transport in airway ciliated cells
Cell Cycle, In press. PMID: 26266958

 Li, F.-Q., Siller, S.S. & Takemaru, K.-I. (2015)
Basal body docking in airway ciliated cells
Oncotarget, Editorial, In press.

Mancini, M., Leo, E. Takemaru, K.-I., Campi, V, Castagnetti, F., Soverini, S., De Benedittis, C., Rosti, G., Cavo, M., Santucci, M.A. & Martinelli, G. (2015)
14-3-3 binding and sumoylation concur to the down-modulation of b-catenin antagonist Chibby1 in chronic myeloid leukemia
PLoS ONE, 10, e0131074. PMCID: PMC4492953

Chen, J., LacLef, C., Moncayo, A., Snedecor, E.R., Yang, N., Li, L., Takemaru, K.-I., Paus, R., Schneider-Maunoury, S. & Clark, R.A. (2015)
The ciliopathy gene Rpgrip1L is essential for hair follicle development
J. Invest. Dermatol., 135, 701-709. PMCID: PMC4340706

Burke, B.C., Li, F.-Q., Cyge, B., Arashiro, T., Brechbuhl, H.M., Chen, X., Siller, S.S., Weiss, M.A., O'Connell, C.B., Love, D., Westlake, C.J., Reynolds, S.D., Kuriyama, R. & Takemaru, K.-I. (2014)
Chibby promotes ciliary vesicle formation and basal body docking during airway cell differentiation
J. Cell Biol., 207, 123-137. PMCID: PMC4195830
"Featured on Journal Cover and highlighted in “In This Issue”.

Lee, Y.L., Sante, J., Comerci, C., Cyge, B., Menezes, L.F., Li, F.-Q., Germino, G.G., Moerner, W.E., Takemaru, K.-I. & Stearns. T. (2014)
Cby1 promotes Ahi1 recruitment to a ring-shaped domain at the centriole-cilium interface and facilitates proper cilium formation and function
Mol. Biol. Cell, 25, 2919-2933. PMCID: PMC4230582

Rodriguez, J.P., Coulter, M., Motke, J., Meyer, R., Takemaru, K.-I. & Levine, J. (2014)
Abrogation of b-catenin signaling in oligodendrocyte precursor cells reduces glial scarring and promotes axon regeneration after CNS injury
J. Neurosci., 34, 10285-10297. PMCID: PMC4115138

Mancini, M., Leo, E., Takemaru, K.-I., Campi, V., Borsi, E., Castagnetti, F., Gugliotta, G., Santucci, M.A., & Martinelli, G. (2013)
Chibby drives b-catenin cytoplasmic accumulation leading to activation of the unfolded protein response in BCR-ABL1+ cells
Cell Signal., 25, 1820-1827. PMID: 23707389

Steere, N., Chae, V., Burke, M.C., Li, F.-Q., Takemaru, K.-I. & Kuriyama, R. (2012)
A Wnt/b-catenin pathway antagonist Chibby binds cenexin at the distal end of mother centrioles and functions in primary cilia formation
PLoS ONE, 7, e41077. PMCID: PMC3401179

Kumamoto, N., Gu, Y., Wang, J., Janoschka, S., Takemaru, K.-I., Levine, J. & Ge, S. (2012)
A role for primary cilia in glutamatergic synaptic integration of adult-born neurons
Nat. Neurosci., 15, 399-405. PMCID: PMC3288565

Love, D., Li, F.-Q., Burke, M.C., Cyge, B., Ohmitsu, M., Cabello, M., Larson, J.E., Brody, S.L., Cohen, J.C. & Takemaru, K.-I. (2010)
Altered lung morphogenesis, epithelial cell differentiation and mechanics in mice deficient in the Wnt/b-catenin antagonist Chibby
PLoS ONE, 5, e13600. PMCID: PMC2963606

Li, F.-Q.*, Mofunanya, A., Fischer, V., Hall, J., & Takemaru, K.-I.* (2010)
Nuclear-cytoplasmic shuttling of Chibby controls β-catenin signaling
Mol. Biol. Cell, 21, 311-322. *Co-correspondence. PMCID: PMC2808236

Mofunanya, A., Li, F.-Q., Hsieh, J.-C., & Takemaru, K.-I. (2009)
Chibby forms a homodimer through a heptad repeat of leucine residues in its C-terminal coiled-coil motif
BMC Mol. Biol., 10, 41. PMCID: PMC2686680

Voronina, V.A., Takemaru, K.-I.*, Treuting, P., Love, D., Grubb, B.R., Hajjar, A.M., Adams, A., Li, F.-Q. & Moon, R.T.* (2009)
Inactivaton of Chibby affects function of motile airway cilia
J. Cell Biol., 185, 225-233. *Co-correspondence. PMCID: PMC2700371

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. *Co-correspondence. PMCID: PMC2442201
Research Highlight by Kritikou, E. (2008)
AKTing in Wnt pathway.
Nat. Rev. Mol. Cell Biol., 9:584.

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. PMCID: PMC1900052

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. PMID: 12712206
News and Views by Greaves, S. (2003)
Small changes in Wnt signalling.
Nat. Cell Biol., 5: 387.

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. PMCID: PMC2175158

Dept. of Pharmacology BST 7-182
Stony Brook, NY 11794-8651
Phone: (631) 444-7976
Fax: (631) 444-3218
E-mail: ken-ichi.takemaru@stonybrook.edu