SECTION

Division of Gene Structure and Function Division of Gene Regulation and Signal Transduction
Division of Developmental Biology Division of Pathophysiology
Division of Gene Therapy and Genome Editing  
Division of Pathophysiology
概要 Research Summary

Figure 1

Figure 2

Musculoskeletal tissues, such as bone, cartilage and skeletal muscle, regulate each other through systemic and local factors. The transforming growth factor-β(TGF-β) family is one of the most important growth factors for various tissues (Figure 1). Some members of the TGF-β family are essential for development of skeletal tissues and for fracture healing through cartilaginous callus formation. Some others suppress skeletal muscle mass. Our group is working on the physiological and pathological roles of the TGF-β family and is trying to develop novel treatments and diagnostic methods for the related diseases.

Fibrodysplasia ossificans progressiva (FOP) is a rare disease characterized by progressive heterotopic (unusual) bone formation in soft tissues, such as skeletal muscle, tendon and ligament. In the last decay, we and others showed that FOP is caused by genetic gain-of-function mutations in ALK2, which is a transmembrane serine/threonine kinase receptor for the TGF-β family. We are developing several ALK2 inhibitors as potential therapeutics for FOP in collaborating with not only other research groups but patients with FOP. We would like to make someone smile through our scientific activities.

スタッフ Staff
Professor Takenobu Katagiri
Instructor Sho Tsukamoto
Instructor Yutaka Nakachi
Assistant Mai Kuratani
Outside Instructor Akihiro Tomoyasu
Technical Assistant Misato Okubo
Project Technical Assistant Noriko Sekine
Project Technical Assistant Yuzuru Iwanaga
Project Assistant Staff Kyoko Oshida
テーマ Research Projects
1)
Development of novel drugs for fibrodysplasia ossificans progressiva (FOP)
2)
Elucidation of the functional network and regulatory mechanisms of musculoskeletal tissues, such as bone, cartilage and skeletal muscle
3)
Elucidation of the roles of the TGF-β family
文献 Selected Publications
Olsen OE, Sankar M, Elsaadi S, Hella H, Buene G, Darvekar SR, Misund K, Katagiri T, Knaus P and Holien T. BMPR2 inhibits activin- and BMP-signaling via wild type ALK2. J Cell Sci, in press (2018).
[PMID: 29739878]
Machiya A, Tsukamoto S, Ohte, S, Kuratani M, Fujimoto M, Kumagai K, Osawa K, Suda N, Bullock AN and Katagiri T. Effects of FKBP12 and type II receptors on signal transduction by an ALK2 mutant associated with genetic disorders. Bone 111:101-108 (2018).
[PMID: 29551750]
Katagiri T, Tsukamoto S, Kuratani M. Heterotopic bone induction via BMP signaling: potential therapeutic targets for fibrodysplasia ossificans progressiva. Bone 109:241-250 (2018).
[PMID: 28754575]
Katagiri T, Watabe T. Bone Morphogenetic Proteins. The TGF-βFamily. Cold Spring Harb Perspect Biol 8: a021899 (2016).
[PMID: 27252362]
Katagiri T. A door opens for fibrodysplasia ossificans progressiva. Trends Biochem Sci 41:119-121 (2016).
[PMID: 26654278]
Fujimoto M, Ohte S, Osawa K, Miyamoto A, Tsukamoto S, Mizuta T, Kokabu S, Suda N, Katagiri T. Mutant activin receptor-like kinase 2 in fibrodysplasia ossificans progressiva are activated via T203 by BMP type II receptors. Mol Endocrinol 29:140-152 (2015).
[PMID: 25354296]
Tsukamoto S, Mizuta T, Fujimoto M, Ohte S, Osawa K, Miyamoto A, Yoneyama K, Murata E, Machiya A, Jimi E, Kokabu S, Katagiri T. Smad9 is a novel type of transcriptional regulator in bone morphogenetic protein signaling. Sci Rep 4:7596 (2014).
[PMID: 25534700]
Nojima J, Kanomata K, Takada Y, Fukuda T, Kokabu S, Ohte S, Takada T, Tsukui T, Yamamoto TS, Sasanuma H, Yoneyama K, Ueno N, Okazaki Y, Kamijo R, Yoda T, Katagiri T. Dual roles of Smad proteins in the conversion from myoblasts to osteoblastic cells by bone morphogenetic proteins. J Biol Chem 285:15577-15586 (2010).
[PMID: 20231279]
Fukuda T, Kohda M, Kanomata K, Nojima J, Nakamura A, Kamizono J, Noguchi Y, Iwakiri K, Kondo T, Kurose J, Endo K, Awakura T, Fukushi J, Nakashima Y, Chiyonobu T, Kawara A, Nishida Y, Wada I, Akita M, Komori T, Nakayama K, Nanba A, Maruki Y, Yoda T, Tomoda H, Yu PB, Shore EM, Kaplan FS, Miyazono K, Matsuoka M, Ikebuchi K, Ohtake A, Oda H, Jimi E, Owan I, Okazaki Y, Katagiri T. Constitutively activated ALK-2 and increased Smad1/5 cooperatively induce BMP signaling in fibrodysplasia ossificans progressiva. J Biol Chem 284:7149-7156 (2009).
[PMID: 18684712]
Yu PB, Deng DY, Lai CS, Hong CC, Cuny GD, Bouxsein ML, Hong DW, McManus PM, Katagiri T, Sachidanandan C, Kamiya N, Fukuda T, Mishina Y, Peterson RT, Bloch KD. BMP type I receptor inhibition reduces heterotopic ossification. Nat Med 14: 1363-1369 (2008).
[PMID: 19029982]
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