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Abstracts from the Human Genome Meeting 2018
Human Genomics2018Vol. 12(S1)
Wai-Hung Ho, Irene Oi-Lin, Ng, Keiko Yamazaki, Yasuo Takahashi, Yukako Katsura, Yayoi Nishida, Yoichiro Kamatani, Michiaki Kubo, Satoshi Asai, Yi-Ching Lee, Yun-Wen Lin, Yuan-Tsong Chen, Silvia Ravera, Nancy Carrasco, Joel Gelernter, Renato Polimanti, Shu Diao, Zhipeng Fan, Giovanni Pascarella, Kosuke Hashimoto, Annika Busch, Anton Kratz, Shigeo Murayama, Shinji Saiki, Stefano Gustincich, Piero Carninci, Jiangshan Shen, Yujun Sheng, Chao Yang, Yongfei Wang, Mengbiao Guo, Yu Lau, Wanling Yang, Xuejun Zhang, Yeojun Yun, Han-Na Kim, Eun-Ju Lee, Hyung-Lae Kim, Han-Na Kim, Hyung-Lae Kim, Han-Na Kim, Hyung-Lae Kim, Hyung-Lae Kim, Takeru Abe, Hajime Nishimura, Kazuaki Kojima, Hiroyuki Sanjo, Takuya Sato, Harukazu Suzuki, Takehiko Ogawa, Takahiro Suzuki, Emily Mccann, Miho Toyama, Yuto Takasaki, Branko Aleksic, Tomoo Ogi, Norio Ozaki, Subinoy Biswas, Christian Schnbach, Naveed Wasif, Asia Parveen, Fareeha Ashraf, Ehtsham Ali, Guntram Borck, T Cannon, J Kaprio, J Lonnqvist, M Huttunen, M Koskenvuo, G Genovese, M Fromer, E Stahl, D Ruderfer, K Chambert, M Landen, J Moran, S Purcell, P Sklar, P Sullivan, S Petrovski, Q Wang, E Heinzen, A Allen, D Goldstein, A Gonzalez-Mantilla, A Moreno-De-Luca, D Ledbetter, C Martin, R Young, A Forrest, Baumgart, Liu, Farh, Raine, A Suzuki, R Yamada, X Chang, S Tokuhiro, T Sawada, M Suzuki, M Nagasaki, M Nakayama-Hamada, R Kawaida, M Ono, M Ohtsuki, H Furukawa, S Yoshino, M Yukioka, S Tohma, T Matsubara, S Wakitani, R Teshima, Y Nishioka, A Sekine, A Iida, A Takahashi, T Tsunoda, Y Nakamura, K Yamamoto, Y Okada, D Wu, G Trynka, T Raj, C Terao, K Ikari, Y Kochi, K Ohmura, A Suzuki, A Suzuki, Y Kochi, H Shoda, Y Seri, K Fujio, T Sawada, R Yamada, K Yamamoto, M Muratani, B Logsdon, J Mezey, X Cai, A Bazerque, G Giannakis, A Boyle, Y Li, J Pritchard, C Carrieri, L Cimatti, M Biagioli, A Beugnet, S Zucchelli, S Fedele, S Zucchelli, F Fasolo, R Russo, L Cimatti, L Patrucco, H Takahashi, A Indrieri, C Grimaldi, S Zucchelli, R Tammaro, S Gustincich, B Franco, A Gusev, A Ko, H Shi, G Bhatia, Chung Penninx, B, E Gamazon, H Wheeler, K Shah, S Mozaffari, K Aquino-Michaels, R Carroll, A Terada, M Okada-Hatakeyama, K Tsuda, J Sese, A Fujimoto, C Trapnell, B Williams, G Pertea, A Mortazavi, G Kwan, M Van Baren, B Li, C Dewey, A Roberts, L Pachter, R Patro, G Duggal, M Love, R Irizarry, C Kingsford, R Patro, S Mount, C Kingsford, N Bray, H Pimentel, P Melsted, L Pachter, B Kaczkowski, Y Tanaka, H Kawaji, A Sandelin, R Andersson, M Itoh, M Horie, B Kaczkowski, M Ohshima, H Matsuzaki, S Noguchi, Y Mikami, Kosuke Goto, Katsuhiko Mineta, Takashi Gojobori, Kaust, T Polderman, C Wraw, I Deary, C Gale, G Der, G Davies, G Davies, S Sniekers, J Trampush, D Zabaneh, V Jackson-Lewis, S Przedborski, Z Wang, M Gerstein, M Snyder, Shuhei Noguchi 1 ; Hasegawa 1, Hideya Kawaji, Aya Nonaka, Takanori Fujita, Genta Nagae, Akihiro Suzuki, Amane Tagashira, Hiroyuki Aburatani, A, S.-K Chu, H.-C Yang, Z Mihaly, M Kormos, A Lanczky, Z Tang, O Luo, X Li, M Zheng, J Zhu, P Szalaj, P Trzaskoma, A Magalska, J Wlodarczyk, B Ruszczycki, P Michalski, E Piecuch, P Wang, D Wang, S Tian, M Penrad-Mobayed, L Sachs, X Ruan, C Wei, E Liu, G Wilczynski, D Plewczynski, G Li, Y Ruan, P Tang, Z Michalski, P Pietal, M Luo, O Sadowski, M Li, X Radew, K Ruan, Y Plewczynski, D, P Szalaj, P Michalski, P Wrblewski, Z Tang, M Kadlof, G Mazzocco, Y Ruan, D Plewczynski, A Auton, L Brooks, R Durbin, E Garrison, H Kang, J Korbel, J Marchini, S Mccarthy, G Mcvean, G Abecasis, J Mark, Ashley Chaisson, Xuefang Sanders, Ankit Zhao, Malhotra, Ryan Mills, Tobias Marschall, Jan Korbel, Evan Eichler, Charles Lee, J Michiel, De Hoon 1, R Alistair, Forrest, D De Rie, I Abugessaisa, T Alam, E Arner, P Arner, H Ashoor, G strm, M Babina, N Bertin, A Burroughs, A Carlisle, C Daub, M Detmar, R Deviatiiarov, A Fort, C Gebhard, D Goldowitz, S Guhl, T Ha, J Harshbarger, A Hasegawa, K Hashimoto, M Herlyn, P Heutink, K Hitchens, C Hon, E Huang, Y Ishizu, C Kai, T Kasukawa, P Klinken, T Lassmann, C Lecellier, W Lee, M Lizio, V Makeev, A Mathelier, Y Medvedeva, N Mejhert, C Mungall, S Noma, M Ohshima, M Okada-Hatakeyama, H Persson, P Rizzu, F Roudnicky, P Saetrom, H Sato, J Severin, J Shin, R Swoboda, H Tarui, H Toyoda, K Vitting-Seerup, L Winteringham, Y Yamaguchi, K Yasuzawa, M Yoneda, N Yumoto, S Zabierowski, P Zhang, C Wells, K Summers, H Kawaji, A Sandelin, M Rehli, Consortium, Y Hayashizaki, P Carninci, Arr Forrest, De Hoon, Mjl, M Friedlnder, S Mackowiak, N Li, Chen Rajewsky, N
Abstract
Activating mutations of fibroblast growth factor receptor 3 (FGFR3) cause various skeletal dysplasias and are also associated with certain cancers. Because there are no known specific pharmaceutical inhibitors of FGFR3, we established a cell-based protein translocation assay system that can monitor FGFR3 activity and be used for high throughput screening of complex mixtures. With this system we identified ethanol extract from a plant as a FGFR3 inhibitor and performed bioassay-guided fractionation to identify potent active fractions. The functionality of extract and active fractions were validated in vitro in FGFR3-activated primary multiple myeloma cells. The therapeutic efficacy and safety of the active fractions were further assessed in FGFR3 ACH mice, an achondroplasia mouse model. Oral administration significantly improved growth and dwarfism-related clinical features of the FGFR3 ACH mice. Our results demonstrate the applicability of this discovery approach. The identified plant extracts and active factions hold therapeutic potential for the treatment of FGFR3-activated skeletal dysplasias and cancers.
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