Clinical Biotechnology

We pursue two scientific interests with a particular focus on skeletal tissues (bones and cartilages): (1) manipulation of progenitor cell differentiation and proliferation based on understanding of molecular mechanisms underlying cell fate specification, and (2) development of novel biomaterials fulfilling characteristics required for in vivo use as scaffolds. We aim to develop novel systems for skeletal tissue engineering and regenerative medicine, where cell differentiation and proliferation are directly regulated in situ.

• Understanding of epigenome dynamics and gene regulatory landscape in cell fate specification by genome-scale and bioinformatic approaches
• Identification of bioactive molecules for tissue regeneration, inspired by the gene regulatory landscape in progenitor differentiation and proliferation
• Development of tissue-development modeling systems using pluripotent stem cells
• Development of tissue-inductive implant devices integrating tissue-regeneration signals and highly functional and biocompatible biomaterials
• Development of theoretical systems and human resources that integrate medical biology and engineering through medicine-engineering collaborations, international collaborations, and industry-academia collaborations

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