讲座题目：“Mesenchymal stem cells in craniofacial tissue homeostasis and regeneration”

报  告 人：柴阳（博士） 教授

        美国南加州大学牙医学院副院长/颅面部分子生物学中心主任  

时       间：2015年4月29日（星期三）  上午 10:00 – 11:30

地       点：杭州师范大学生科院发育与再生研究所一楼会议室

个人简介：

       美国南加州大学DDS、Ph.D.，颅颌面部发育国际著名专家。现任南加州大学Ostrow牙医学院教授、副院长、颅面部分子生物学中心主任。

柴博士主要从事神经嵴细胞对颅面部器官发育及畸形的分子调控机理研究。多年来，他的工作主要通过利用不同的基因修饰小鼠模型，研究哺乳动物牙齿、上腭、颌骨、舌头和颅骨等颅面部器官的形成、以及组织间相互作用对形态决定的影响。同时，他在干细胞与颅面部器官再生研究领域也颇有建树，是该领域的国际领军人物。近年来，他在动物模型与人类出生缺陷的比较研究中取得突破性成果，首创了“在胚胎发育过程中通过信号通路的调控可以成功挽救颅面部畸形”的理论，并在该领域奠定了具有国际一流研究水准的基础。

      柴博士曾获得2011国际牙科研究协会“杰出科学家奖”，是美国人文与科学学会成员，担任美国《Developmental Biology》和《Journal of Bone and Mineral Research》杂志的编委、美国牙科与颅面部研究所的科学顾问、美国NIH和英国Welcome Trust等科研基金评审专家。至今已发表高水平的原创性学术论文110余篇，主持并完成NIH科研基金等多项科研项目，并撰写了多部著作，他所获的研究成果确定了其在颅颌面部器官发育研究领域的国际领先地位。

代表性文章：

[1]      Li, J., Feng, J., Liu, Y., Ho, T., Grimes, W., Ho, H., Park, S., Wang, S., and Chai, Y. (2015) BMP-SHH signaling network controls epithelial stem cell fate via regulation of its niche in the developing tooth. Developmental Cell, in press.

[2]      Zhong, Z., Zhao, H., Mayo, J., and Chai, Y. (2015) Different requirements for Wnt signaling in tongue myogenic subpopulations, Journal of Dental Research, 94, 421-429.

[3]      Ho, T. V., Iwata, J., Ho, H. A., Grimes, W. C., Park, S., Sanchez-Lara, P. A., and Chai, Y. (2015) Integration of comprehensive 3D microCT and signaling analysis reveals differential regulatory mechanisms of craniofacial bone development. Developmental Biology, 2015 Apr 15;400(2):180-90.

[4]      Zhao, H., Feng, J., Ho, T. V., Grimes, W. C., Urata, M., and Chai, Y. (2015) The suture provides a niche for mesenchymal stem cells of craniofacial bones. Nature Cell Biology, 2015 Apr;17(4):386-96.

[5]      Xie, WB, Li, Z, Shi, N, Guo, X, Tang, J, Ju, W, Han, J, Liu, T, Bottinger, EP, Chai, Y, Jose, PA, Chen, SY. (2014) Smad2 and MRTFB Cooperatively Regulate Vascular Smooth Muscle Differentiation from Neural Crest Cells. Circ Res. 113, 76-86.

[6]      Iwata, J., Suzuki, A., Pelikan, R., Ho, T., Sanchez-Lara, P., Chai, Y. (2014) Modulation of lipid metabolic defects rescues cleft palate in Tgfbr2 mutant mice. Human Molecular Genetics, 23, 182-193.

[7]      Iwata, J., Suzuki, A., Yokota, T., Ho, T.V., Urata, M., Sanchez, P., and Chai, Y. (2014) TGF-b-mediated WNT signaling regulates epithelial-mesenchymal interactions to control muscle development in the soft palate. Development, 141, 909-917.

[8]      Zhao, H., Feng, J., Seidel, K., Shi, S., Klein, O., Sharpe, P., and Chai, Y. (2014) Secretion of Shh by a neurovascular bundle niche supports mesenchymal stem cell homeostasis in the adult mouse incisor. Cell Stem Cell 14, 160-173.

[9]      Han, A., Zhao, H., Li, J., Pelikan, R., and Chai, Y. (2014) ALK5-mediated TGF-β signaling in neural crest cells controls craniofacial muscle development via tissue-tissue interactions. Molecular and Cellular Biology, 34, 3120-3131.

[10]  Pelikan, R., Iwata, J., Chai, Y. and Hacia, J. (2013) Identification of candidate downstream targets of TGFβ signaling during palate development by genome-wide transcript profiling. J. Cellular Biochemistry, 114, 796-807.

[11]  Huang, X. F. and Chai, Y. (2013) Molecular regulatory mechanism of tooth root development. I. J. Oral Biol. 4, 177-181.

[12]  Iwata, J., Suzuki, A., Pelikan, R. C., Ho, T. V., Sanchez-Lara, P. A., Urata, M., Dixon, M. J., and Chai, Y. (2013) Smad4/Irf6 genetic interaction and TGFb-mediated IRF6 signaling cascade are crucial for palatal fusion in mice. Development, 140, 1220-1230.

[13]  Song, Z. C., Liu, C., Iwata, J., Gu, S. P., Suzuki, A., Sun, C., He, W., Shu, R., Li, L., Chai, Y., and Chen, Y. P. (2013) Mice with Tak1-deficiency in neural crest lineage exhibit cleft palate associated with abnormal tongue development. (Chai and Chen, co-correspondence authors) JBC, 288,10440-10450.

[14]  Mima, J., Koshino, A., Oka, K., Uchida, H., Hieda, Y., Nohara, K., Kogo, M., Chai, Y., and Sakai, T. (2013) Regulation of the epithelial adhesion molecule CEACAM1 is important for palate formation. PLoS one, 8, e61653.

[15]  Parada, C., Li, J., Iwata, J., Suzuki, A., and Chai, Y. (2013) CTGF mediates Smad-dependent TGFb signaling to regulate mesenchymal cell proliferation during palate development. Molecular and Cellular Biology, 33, 3482-3493.

[16]  Iwata, J., Suzuki, A., Pelikan, R., Ho, T., and Chai, Y. (2013) Non-canonical transforming growth factor best (TGFb) signaling in cranial neural crest cells causes tongue muscle development defects. JBC, 288, 29760-29770.

[17]  Xu, X., Chen, C., Akiyama, K., Chai, Y., Le, A.D., Wang, Z., and Shi, S. (2013) Gingivae contain neural crest- and mesoderm-derived mesenchymal stem cells. JDR, 92, 825-832.

[18]  Iwata, J., Tung, L., Urata, M., Hacia, J., Suzuki, A., Chaudhry, O., Parada Borja, C., Sanchez-Lara, P., and Chai, Y. (2012) Transforming growth factor beta (TGFb) mediated fibroblast growth factor 9 (FGF9)-pituitary homeobox 2 (PITX2) signaling regulates cell proliferation in palatal mesenchymal cells. JBC, 287, 2353-2363.

[19]  Parada, C., Han, D., and Chai, Y. (2012) Molecular and cellular regulatory mechanism of tongue morphogenesis. JDR 6, 528-535.

[20]  Han, D., Zhao, H., Parada, C., Hacia, J., Bringas, P., and Chai, Y. (2012) TGF-b-Smad4-FGF6 signaling cascade controls myogenic differentiation and myoblast fusion during tongue development. Development, 139, 1640-1650.

[21]  Iwata, J., Hacia, J., Suzuki, A., Sanchez-Lara, P., Urata, M., and Chai, Y. (2012) Modulation of non-canonical TGF-b signaling prevents cleft palate in Tgfbr2 mutant mice. Journal of Clinical Investigation 122, 873-885.

[22]  Parada, C. and Chai, Y. (2012) Roles of BMP signaling pathway in lip and palate development. Front Oral Biol. 16, 60-70.

[23]  Stephens, H., Jensen, B., Stephens H, Jensen B, Carpiaux W, Sedghizadeh P, Chai Y. (2012)
A collaborative approach to advance student research at the University of Southern California.
JCDA 40, 433-439.

[24]  Iwata, J., Parada, C., and Chai, Y. (2011) The mechanism of TGF-b signaling during palatogenesis. Oral Disease, 17, 733-744.

[25] Hochheiser, H, Aronow, BJ, Artinger, K, Beaty, TH, Brinkley, JF, Chai, Y, Clouthier, D, Cunningham, ML, Dixon, M, Donahue, LR, Fraser, SE, Iwata, J, Marazita, ML, Murray, JC, Murray, S, Postlethwait, J, Potter, S, Shapiro, L, Spritz, R, Visel, A, Weinberg, SM, Trainor, PA. (2011) The FaceBase Consortium: A comprehensive program to facilitate craniofacial research. Dev. Biol. 355, 175-182.

[26]  Zhao, H., Li, S., Han, D., Kaartinen, V., and Chai, Y. (2011) Alk5-mediated TGF-b signaling acts upstream of FGF10 to regulate the proliferation and maintenance of dental epithelial stem cells. Molecular and Cellular Biology, 31, 2079-2089.

[27]  Li, J., Huang, X., Xu, X., Mayo, J., Bringas, P., Jiang, R., Wang, S., and Chai, Y. (2011) Smad4-mediated Wnt signaling controls the fate of cranial neural crest cells during tooth morphogenesis. Development, 138, 1977-1989.

[28]  Huang, X.F., Yokoda, T., Iwata, J., and Chai, Y. (2011) Tgf-b mediated FasL-Fas-Caspase pathway is crucial during palatogenesis. JDR, 90, 981-987.

[29]  Huang, X., Xu, X, Bringas, P Jr, Hung, YP, Chai, Y. (2010) Smad4-Shh-Nfic signaling cascade-mediated epithelial-mesenchymal interaction is crucial in regulating tooth root development. JBMR 25, 1167-1178.

[30]  Iwata J, Hosokawa R, Sanchez-Lara PA, Urata M, Slavkin H, Chai Y. (2010) Transforming growth factor beta regulates basal transcriptional regulatory machinery to control cell proliferation and differentiation in cranial neural crest-derived osteoprogenitor cells. J. Biol. Chem. 285, 4975-4982.

[31]  Lu L, Wang J, Zhang F, Chai Y, Brand D, Wang X, Horwitz DA, Shi W, Zheng SG. (2010) Role of Smad and non-Smad signals in the development of Th17 and regulatory T cells, J Immunol, 184, 4295-4306.

[32]  Hosokawa, T., Oka, K., Yamaza, T., Iwata, J., Urata, M., Xu, X., Bringas, P., Nonaka, K., and Chai, Y. (2010) TGF-b mediated FGF10 signaling in cranial neural crest cells controls development of myogenic progenitor cells through tissue-tissue interactions during tongue morphogenesis. Dev. Biol. 341, 186-195.

[33]  Chung, I., Han, J., Iwate, J., and Chai, Y. (2010) Msx1 and Dlx5 function synergistically to regulate frontal bone development. Genesis, The Journal of Genetics and Development, 48, 645-655.

[34]  He F, Xiong W, Wang Y, Matsui M, Yu X, Chai Y, Klingensmith J, Chen Y. (2010) Modulation of BMP signaling by Noggin is required for the maintenance of palatal epithelial integrity during palatogenesis. Dev. Biol. 347, 109-121.

[35]  Jinno, H., Morozova, O., Biernaskie, J.A., Paris, M., Hosokawa, R., Rudnicki, M., Chai, Y., Rossi, F., Marra, M., and Miller, F.D. (2010) Convergent genesis of an adult neural crest-like dermal stem cell from two distinct developmental origins. Stem Cells, 28, 2027-2040.

[36]  Shi, S., Chai, Y., and Slavkin, H (2009) Emerging opportunities for the next generation of dental implants. Dentistry Today, 28, 98-99.

[37]  Hosokawa, R., Deng, X., Takamori, K., Xu, X., Urata, M., Bringas, Jr., P., and Chai, Y. (2009) Epithelial-specific requirement of FGFR2 signaling during tooth and palate development. J. Exp. Zoology 312, 343-350.

[38]  Chung, I., Yamaza, T., Zhao, H., Choung, P., Shi, S., and Chai, Y. (2009) Stem cell property of postmigratory cranial neural crest cells and their utility in alveolar bone regeneration and tooth development. Stem Cells 4, 866-877.

[39]  Zhang, Z., Lan, Y., Chai, Y., and Jiang, R. (2009) Antagonistic actions of Msx1 and Osr2 pattern mammalian teeth into single row. Science 323, 1232-1234.

[40]  Noh, T., Gabet, Y., Cogan, J., Shi, Y., Tank, A., Sasaki, T., Criswell, B., Dixson, A., Lee, C., Tam, J., Kohler, T., Segev, E., Kockeritz, L., Woodgett, J., Muller, R., Chai, Y., Smith, E., Bab, I., and Frenkel, B. (2009) Lef1 haploinsufficiency mice display a low turnover and low bone mass phenotype in a gender- and age-specific manner. PLoS ONE 4, 5438-5448.

[41]  Huang, X., Bringas, P., Slavkin, H., and Chai, Y. (2009) Fate of HERS during tooth root development. Dev. Biol., 334, 22-30.

[42]  Han, J., Mayo, J., Xu, X., Li, JY, Bringas, P., Maas, R., Rubenstein, JLR, and Chai, Y. (2009) Indirect modulation of Shh signaling by Dlx5 affects the oral-nasal patterning of palate and rescues cleft palate in Msx1 null mice. Development, 136, 4225-4233.

[43]  Oka, K., Oka, S., and Chai, Y. (2009) The role of TGF-b signaling in cranial neural crest cells during mandibular and tooth development. J. Oral Biosci. 51, 143-150.

[44]  Takamori, K., Hosokawa, R., Xu, X., Deng, X-M, Bringas, Jr., P., and Chai, Y. (2008). Epidermal fibroblast growth factor receptor 1 regulates enamel formation. JDR 87, 238-243.

[45]  De Langhe SP, Carraro G, Tefft D, Li C, Xu X, Chai, Y , Minoo P, Hajihosseini MK, Drouin J, Kaartinen V, Bellusci S. (2008) Formation and differentiation of multiple mesenchymal lineages during lung development is regulated by beta-catenin signaling. PLoS ONE, 30, 1516-1527.

[46]  Chen H, Zhuang F, Liu YH, Xu B, Del Moral P, Deng W, Chai Y, Kolb M, Gauldie J, Warburton D, Moses HL, Shi W. (2008) TGF-beta receptor II in Epithelia Versus Mesenchyme Plays Distinct Role in Developing Lung.  Eur Respir J. 32, 285-295.

[47]  Zhao, H., Oka, K., Bringas, P., Kaartinen, V. and Chai, Y. (2008). TGF-b type I receptor Alk5 regulates tooth initiation and mandible patterning in a type II receptor-independent manner. Dev. Biol. 320, 19-29.

[48]  Anthwal, N., Chai, Y., and Tucker, A.S. (2008) The role of transforming growth factor-b signalling in the patterning of the dentary of the mouse. Dev Dyn. 237, 1604-1613.

[49]  Oka, K., Oka, S., Hosokawa, R., Bringas, P., Brockhoff, H.C., Nonaka, K., and Chai, Y. (2008). TGF-b-mediated Dlx5 signaling plays a crucial role in osteo-chondroprogenitor cell lineage determination during mandible development. Dev. Biol. 321, 303-309.

[50]  Xing, Y., Li, C., Hu, L., Tiozzo, C., Li, M., Chai, Y., Bellusci, S., Anderson, S., and Minoo, P. (2008) Mechanisms of TGF-b inhibition of lung endodermal morphogenesis: The role of Tgfbr2, Smads, Nkx2.1 and Pten. Dev. Biol. 320, 340-350.

[51]  Yamamoto, S., Fukumoto, E., Yoshizaki, K., Iwamoto, T., Yamada, A., Tanaka, K., Suzuki, H., Aizawa, S., Arakaki, M., Yuasa, K., Oka, K., Chai, Y., Nonaka, K., and Fukumoto, S. (2008) PDGF regulates salivary gland morphogenesis via FGF expression. J. Biol. Chem. 283, 23139-23149.

[52]  Xu, X., Han, J., Ito, Y., Bringas, P., Deng, CX, and Chai, Y. (2008) Ectodermal Smad4 and p38 MAPK are functionally redundant in mediating TGF-b/BMP signaling during tooth and palate development. Dev. Cell 15, 322-329.