Junya Toguchida, M.D., Ph.D. Professor
Skeletal system is a major connective tissue system that is composed of organs including bones, ligament, tendons, cartilages and muscles. We are trying to develop new treatments for skeletal system diseases by following approaches. 1. Establishment of efficient methods to induce bones, cartilages, or ligaments from iPSCs, 2. Clarification of pathogenesis of skeletal system diseases using patient-derived iPSCs, and 3. Clarifying the mechanism underling the development of sarcomas, malignant tumors developed in the skeletal system.
Research and EducationRegarding skeletal systems, we are approaching various aspects of their mechanisms and pathogeneses. Using iPSCs obtained from patients with Fibrodysplasia Ossificans Progressiva (FOP), a disease with systemic ectopic ossification, we found de novo signaling pathway via mutated ACVR1 gene, followed by ectopic hypertrophic formation of chondrocytes and resulting ectopic endochondral ossification. Also, we are figuring out the pathogeneses of ectopic bone formation in ligaments (ossification of posterior longitudinal ligament, OPLL). Abnormal hypertrophy of growth plates in CINCA syndrome is another project using patient-derived iPSCs. Furthermore, new differentiation methods for skeletal systems are launching. iPSCs technology is also applied for investigating the mechanism of sarcoma development, particularly with genome-editing technique.
Students and researchers from various nations are discussing with each other and working on their own projects.
Left: 3DCT image of a patient with FOP. Note the intensive ectopic bone formation in the back and thigh.
Right: Ectopic bone in mice induced by human cells derived from FOP-iPSCs.
Members of the laboratory
- Hino K, Ikeya M, Horigome K, Matsumoto Y, Ebise H, Nishio M, Sekiguchi K, Shibata M, Nagata S, Matsuda S, Toguchida J. Neofunction of ACVR1 in fibrodysplasia ossificans progressiva. Proc Natl Acad Sci U S A. 2015;112(50):15438-43.
- Tamaki S, Fukuta M, Sekiguchi K, Jin Y, Nagata S, Hayakawa K, Hineno S, Okamoto T, Watanabe M, Woltjen K, Ikeya M, Kato T Jr, Toguchida J. SS18-SSX, the Oncogenic Fusion Protein in Synovial Sarcoma, Is a Cellular Context-Dependent Epigenetic Modifier. PLoS One. 2015;10(11):e0142991
- Yokoyama K, Ikeya M, Umeda K, Oda H, Nodomi S, Nasu A, Matsumoto Y, Izawa K, Horigome K, Kusaka T, Tanaka T, Saito MK, Yasumi T, Nishikomori R, Ohara O, Nakayama N, Nakahata T, Heike T, Toguchida J. Enhanced chondrogenesis of iPS cells from neonatal-onset multisystem inflammatory disease occurs via the caspase-1-independent cAMP/PKA/CREB pathway. Arthritis Rheumatol. 2015;67(1):302-14.
- Jin Y, Elalaf H, Watanabe M, Tamaki S, Hineno S, Matsunaga K, Woltjen K, Kobayashi Y, Nagata S, Ikeya M, Kato T Jr, Okamoto T, Matsuda S, Toguchida J. Mutant IDH1 Dysregulates the Differentiation of Mesenchymal Stem Cells in Association with Gene-Specific Histone Modifications to Cartilage- and Bone-Related Genes. PLoS One;10(7):e0131998.
- Fukuta M, Nakai Y, Kirino K, Nakagawa M, Sekiguchi K, Nagata S, Matsumoto Y, Yamamoto T, Umeda K, Heike T, Okumura N, Koizumi N, Sato T, Nakahata T, Saito M, Otsuka T, Kinoshita S, Ueno M, Ikeya M, Toguchida J. Derivation of mesenchymal stromal cells from pluripotent stem cells through a neural crest lineage using small molecule compounds with defined media. PLos One, 2014;9(12):e112291.
LaboratoryDepartment of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto University
Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application (CiRA), Kyoto University
Institute for Advancement of Clinical and Translational Science (iACT), Kyoto University Hospital.
Professor: Junya Toguchida
Associate Professor: Hiroyuki Yoshitomi (Frontier, CiRA), Ken Okamoto(iACT)
Assistant Professor: Cantas Alev (CiRA), Yonghui Jin (iACT)
Researcher: Sakura Tamaki (Frontier)