The newly founded Department of Cellular Regenerative Medicine has developed the world’s first methods of direct conversion from human fibroblasts to neural cells using chemical compounds only (CiN cells: chemical compound-induced neuronal cells). We are now focusing on the five research projects listed below. CiN cells are epoch-making because gene transfection is not needed in any steps.
 CiN cells, which are completely different from ES and iPS cells, represent a breakthrough for new regenerative medicine and offer high potential to develop new clinical applications to neurodegenerative disorders (Alzheimer’s disease, ALS etc.), spinal injury, neuropathy and retinopathy.

1. Mechanisms for direct conversion of human fibroblasts into CiN cells (chemical compound-induced neuronal cells).
2. Genetic characterization of CiN cells.
3. Functional analysis of CiN cells in vitro and in vivo.
4. Development of derivative methods for conversion of human fibroblasts into cell species other than CiN cells with defined chemical compounds.
5. Development of new therapeutic strategies for neurodegenerative disorders (Alzheimer’s disease, ALS, etc.), spinal injury, neuropathy and retinopathy by using CiN cells.

1. Takeda Y, Dai P*. A developed serum-free medium and an optimized chemical cocktail for direct conversion of human dermal fibroblasts into brown adipocytes. Sci. Rep., 10 (1): 3775 (2020).(*Corresponding author)
2. Takeda Y, Harada Y, Yoshikawa T, Dai P*. Chemical compound-based direct reprogramming for future clinical applications. Biosci. Rep., 38: BSR20171650 (2018). (*Corresponding author)
3. Takeda Y, Harada Y, Yoshikawa T, Dai P*. Direct conversion of human fibroblasts to brown adipocytes by small chemical compounds. Sci. Rep., 7: 4304 (2017). (*Corresponding author)
4. Dai P*, Harada Y, Takamatsu T. Highly efficient direct conversion of human fibroblasts to neuronal cells by chemical compounds. J. Clin. Biochem. Nutr., 56: 166-170 (2015). (*Corresponding author)
5. Dai P*, Harada Y, Miyachi H, Tanaka H, Kitano S, Adachi T, Suzuki T, Hino H, Takamatsu T*. Combining TGF-β signal inhibition and connexin43 silencing for iPSC induction from mouse cardiomyocytes. Sci. Rep.,4: 7323 (2014). (*Corresponding author)
6. Hatakeyama T*, Dai P*, Harada Y, Hino H, Tsukahara F, Maru Y, Otsuji E, Takamatsu T.Connexin43 functions as a novel interacting partner of heat shock cognate protein 70.Sci. Rep., 3:2719(2013).(*equally contributed)
7. Suzuki T, Dai P*, Hatakeyama T, Harada Y, Tanaka H, Yoshimura N, Takamatsu T*. TGF-β signaling regulates pancreatic β-cell proliferation through control of cell cycle regulator p27 expression.Acta Histochem. Cytochem., 46, 51-58(2013). (*Corresponding author)
8. Taniguchi D*,Dai P*,Hojo T, Yamaoka Y, Kubo T, Takamatsu T. Low-energy laser irradiation promotes synovial fibroblast proliferation by modulating p15 subcellular localization.Lasers Surg. Med., 41, 232-239 (2009). (*equally contributed)
9. Asazuma-Nakamura Y*, Dai P*, Harada Y, Jiang Y, Hamaoka K, Takamatsu T. Cx43 contributes to TGF-β signaling to regulate differentiation of cardiac fibroblasts into myofibroblasts. Exp. Cell Res.,315, 1190-1199 (2009). (*equally contributed)
10. Dai P*, Nakagami T, Tanaka H, Hitomi T, Takamatsu, T*.Cx43 mediates TGF-β signaling through competitive Smads binding to microtubules. Mol. Biol. Cell, 18, 2264-2273 (2007). (*Corresponding author)
11. Tanabe T, Oyamada M, Fujita K, Dai P, Tanaka H, Takamatsu T. Multiphoton excitation-evoked chromophore-assisted laser inactivation using green fluorescent protein.Nat. Methods, 2, 503-505 (2005).
12. Dai P, Akimaru H, Ishii S. A hedgehog-responsive region in the Drosophila wing disc is defined by Debra-mediated ubiquitination and lysosomal degradation of Ci. Dev. Cell, 4, 917-928 (2003).(Selected as a featured article)
13. Dai P, Shinagawa T, Nomura T, Harada J, Kaul SC, Wadhwa R, Khan MM,　Akimaru H, Sasaki H, Colmenares C, Ishii S. Ski is involved in transcriptional regulation by the repressor and full-length form of Gli3. Genes Dev., 16, 2843-2848 (2002).
14. Dai P, Akimaru H, Tanaka Y, Maekawa T, Nakafuku M, Ishii S. Sonic hedgehog-induced activation of Gli1 promotor mediated by GLI3. J. Biol. Chem., 274, 8143-8152 (1999).
15. Akimaru H, Chen Y,Dai P, Hou DX, Nonaka M, Smolik SM, Armstrong S,　Goodman R, Ishii S.Drosophila CBP is a co-activator of cubitus interruptus in hedgehog signalling. Nature, 386, 735-738 (1997).
16. Dai P, Akimaru H, Tanaka Y, Hou DX, Yasukawa T, Kanei-Ishii C, Takahashi T, Ishii S. CBP as a transcriptional coactivator of c-Myb.Genes Dev., 10, 528-540 (1996).