臨床医工学

本部門では、骨発生・骨代謝機構の根本原理の理解と骨格系疾患の分子病態の理解に基づく、骨格系疾患に対する新たな治療戦略の創出を目指しています。幹細胞・動物モデル・ヒトサンプルを用いたデータ駆動型研究を基盤に、バイオエンジニアリング研究を発展させ、創薬プラットホームを確立するとともに、再生医療へ応用します。工学系研究科・東大病院との密な連携を通して、その融合学理の確立とそれを担う人材の育成を目標とします。

• オミクス解析・一細胞解析・バイオインフォマティクスを駆使した、骨発生・骨修復における骨格系細胞・血球系細胞のエピゲノムダイナミクス、遺伝子制御ネットワークの解明
• 発生機序・病態解明を目指した、一細胞解析・分子バーコード・ゲノム編集技術を駆使したスクリーニングシステムの開発
• 多能性幹細胞を用いた骨発生・骨疾患モデリングシステムの開発
• 高機能・高生体適合性バイオマテリアルと組織再生シグナルの知見に基づいた、組織再生を誘導するインプラントデバイスの開発
• 超高齢社会日本の医療課題、特に大腿骨近位部骨折と骨粗鬆症の新たな治療ターゲットを創出する基盤研究
• 医工連携に基づく共同研究、国際共同研究・産学連携研究を通じた融合学理の確立とそれを担う人材の育成

1. Tani S, Chung UI, Ohba S, Hojo H. Understanding paraxial mesoderm development and sclerotome specification for skeletal repair. Exp Mol Med. 52(8):1166-1177, 2020
2. Zujura D, Kanke K, Onodera S, Tani S, Lai J, Azuma T, Xin X, Lichtler AC, Rowe DW, Saito T, Tanaka S, Masaki H Nakauchi H, Chung UI, Hojo H and Ohba S. Stepwise strategy for generating osteoblasts from human pluripotent stem cells under fully defined xeno-free conditions with small-molecule inducers. Regenerative Therapy 14, 19-31, 2020
3. Okada H, Kajiya H, Omata Y, Matsumoto T, Sato Y, Kobayashi T, Nakamura S, Kaneko Y, Nakamura S, Koyama T, Sudo S, Shin M, Okamoto F, Watanabe H, Tachibana N, Hirose J, Saito T, Takai T, Matsumoto M, Nakamura M, Okabe K, Miyamoto T, Tanaka S.　CTLA4-Ig directly inhibits osteoclastogenesis by interfering with intracellular calcium oscillations in bone marrow macrophages. J Bone Miner Res. 34(9):1744-1752, 2019
4. Zujur D, Kanke K, Hojo H, Lichtler AC, Chung UI, Ohba S: Three-dimensional system enabling the maintenance and directed differentiation of pluripotent stem cells under defined conditions. Sci Adv 3(5):e1602875, 2017
5. Hayashi K, Okamoto F, Hoshi S, Katashima T, Zujur D, Li X, Shibayama M, Gilbert EP, Chung UI, Ohba S, Oshika T, Sakai T: Fast-forming hydrogel with ultralow polymeric content as an artificial vitreous body. Nat Biomed Eng 1:44, 2017
6. Hojo H, McMahon AP, Ohba S: An emerging regulatory landscape for skeletal development. Trends Genet 32(12):774-787, 2016
7. Aini H, Itaka K, Fujisawa A, Uchida H, Uchida S, Fukushima S, Kataoka K, Saito T, Chung UI, Ohba S: Messenger RNA delivery of a cartilage-anabolic transcription factor as a disease-modifying strategy for osteoarthritis treatment. Sci Rep 6:18743, 2016
8. He X, Ohba S, Hojo H, McMahon AP: AP-1 family members act with Sox9 to promote chondrocyte hypertrophy. Development 143(16):3012-3023, 2016
9. Hojo H, Ohba S, He X, Lai LP, McMahon AP: Sp7/Osterix is restricted to bone-forming vertebrates where it acts as a Dlx co-factor in osteoblast specification. Dev Cell 37(3):238-253, 2016
10. Ohba S, He X, Hojo H, McMahon AP: Distinct transcriptional programs underlie Sox9 regulation of the mammalian chondrocyte. Cell Rep 12(2):229-243, 2015
11. Kanke K, Masaki H, Saito T, Komiyama Y, Hojo H, Nakauchi H, Lichtler AC, Takato T, Chung UI, Ohba S: Stepwise differentiation of pluripotent stem cells into osteoblasts using four small molecules under serum-free and feeder-free conditions. Stem Cell Reports 2(6):751-760, 2014
12. Maeda Y, Hojo H, Shimohata N, Choi S, Yamamoto K, Takato T, Chung UI, Ohba S: Bone healing by sterilizable calcium phosphate tetrapods eluting osteogenic molecules. Biomaterials 34(22):5530-5537, 2013
13. Hojo H, Ohba S, Taniguchi K, Shirai M, Yano F, Saito T, Ikeda T, Nakajima K, Komiyama Y, Nakagata N, Suzuki K, Mishina Y, Yamada M, Konno T, Takato T, Kawaguchi H, Kambara H, and Chung UI. Hedgehog-Gli activators direct osteo-chondrogenic function of bone morphogenetic protein toward osteogenesis in the perichondrium. J Biol Chem 288, 9924-9932, 2013
14. Hojo H, Ohba S, Yano F, Saito T, Ikeda T, Nakajima K, Komiyama Y, Nakagata N, Suzuki K, Takato T, Kawaguchi H, Chung UI: Gli1 protein participates in the hedgehog-mediated specification of the osteoblast lineage during endochondral ossification. J Biol Chem 287(21):17860-17869, 2012