Motomi Enomoto-Iwamoto, DDS, PhD

https://www.ncbi.nlm.nih.gov/myncbi/motomi.enomoto-iwamoto.1/bibliography/public/?sortby=pubDate&sdirection=ascending

Analysis of the chondrocyte differentiation process during endochondral ossification.

Chondrocytes play essential roles in endochondral bone formation. The initial chondrogenic induction defines the site of bone formation. Proliferation and matrix production by chondrocytes are linked to the bone growth. Maturation of chondrocytes controls the rate of cartilage-to-bone transition.  A series of this complex process is regulated by multiple growth factors, hormones, vitamins and morphogenetic factors.  Impairment of any process results in skeletal mal-formation. Our research focus is to identify and define the role of critical regulators, and ultimately understand how temporo-spatial expression of critical regulatory molecules and their interplay enables sequential cyto-differentiation of chondrocytes, leading to bone growth. Specifically, we are studying cross-talk between Wnt/beta-catenin signaling and retinoid signaling in regulation of endochondral ossification

Aberrant cell signaling in cartilage-related orthopaedic disorders.

Our research team studies cellular and molecular mechanisms by which cartilage-related orthopedic disorders are caused. We are focusing cartilage tumors, such as osteochondromas. In use of combination of transgenic mouse technology and animal surgery experiments, we have demonstrated that aberrant Wnt/beta-catenin signaling causes or is associated with formation of periosteal cartilage tumor formation. Currently, we are studying pharmacological modalities to correct alterations of Wnt/beta-catenin signaling and other molecular signaling pathways. Collaboration with clinician scientists in our department, we are expanding our interests to other cartilage tumors such as chondrosarcomas and joint degenerative diseases.

Local progenitor cells in epiphysis and tendon.

Resident progenitors contribute to development, renewal and repair of organs and tissues. We are studying on distribution, fate and function of progenitors in epiphysis (articular cartilage and growth plate) and tendon. In the mouse models, we have located candidate source of progenitors that supply new cells to growth plate and articular cartilage during postnatal skeletal growth. We are studying whether and how these progenitors contribute to tissue repair after injury using growth plate injury and osteoarthritis models.

We have demonstrated that progenitor cells appear in injured tendons in mice. This is also true in human. Collaboration with clinician scientists, we aim to define nature of tendon progenitors in human injured tendons and develop therapeutic tools and concepts that stimulate tendon differentiation and inhibit de-differentiation of resident tendon progenitors, leading to improvement of structural and functional recovery of injured tendons.

1998  Investigator award from Japanese Society for Cartilage Metabolism

1998  Yumikura award from Society of Osaka University Faculty of Dentistry

1R01AR073181-01A1 (Enomoto-Iwamoto, PI)                                 2/1/19 – 1/31/2024

NIH/NIAMS

Development of Pharmacological Treatment of Osteochondromas

1R01AR070099-01 (Enomoto-Iwamoto, PI)                                      07/12/2016 – 4/30/2021

NIH/NIAMS

Stimulation of Tendon Repair by Metabolic Modifiers

Role: PI

9R01AR062908 (Pacifici and Enomoto-Iwamoto, MPI)                        09/01/16-08/31/21               

NIH/NIAMS                                                                            

Mechanisms of Synovial Joint Formation

Role: MPI

2RO1AR056837-07A1 (Iwamoto)                                                      04/01/2016-03/31/2021

Regulation of Skeletal Growth by Nuclear Retinoid Receptors

Role: CoI

Membership in Professional and Scientific Societies

National:

            1991- Present  American Society for Cell Biology

            2005- Present  Orthopaedic Research Society

            2013- Present  Osteoarthritis Research Society International

            2013- Present  American Bone and Mineral Research Society

International:

            1983- 2010  Japanese Society of Bone Metabolism

            1995- Present  Japanese Society of Cartilage Metabolism

Grant reviews

Wellcome trust (UK, 2008, 2010), Medical Research Council Grant (UK, 2009), Reumafonds (the Dutch Arthritis Association, 2008), Orthopaedic Research and Education Foundation (2012), NIH (2013-, Ad hoc), Medical Research Council (UK, 2016)

Editorial Positions

Served as an editorial board member: American Journal of Pathology (2013-)

Served as a reviewer for scientific journals: American Journal of Pathology (2006-); Arthritis & Rheumatism (2007-); Osteoarthritis & Cartilage (2005-); Experimental Cell Research (2011-); Arthritis Research and Therapy (2010-); PLoS ONE (2011-), Journal of Bone and Mineral Research (2002-), Cell Proliferation (2011), Bone (2007-), Sci Rep (2015-), Nature protocol (2015)

Academic and Institutional Committees:

2008-2009       A member of Research Committee (Thomas Jefferson University)

2010                A member of Curriculum Committee (Graduate Program in Cell and Developmental Biology, Thomas Jefferson University)

2013-2015                   A member of PhD thesis committee (Thomas Jefferson University)

2013-               A member of Steering committee (University of Pennsylvania)

Major Teaching Responsibility:

1988-1989   Biochemistry and Oral Biochemistry, Required for third year Faculty of

             Dentistry Osaka University)

1992- 2002   Biochemistry, Cell Biology, Molecular Biology and Oral Biochemistry,

             Required for second year Faculty of Dentistry Osaka University

1994-2002   Oral Biochemistry, Graduate course of Faculty of Dentistry Osaka University

                  Mentored four Ph.D. students.

1988-1989   Biochemistry, Required for first year students of Osaka Industrial College

            School of Dental Health Care, Osaka

1992-2002   Biochemistry, Required for first year students of Osaka College School of  

             Dental Health, Osaka

2002-      Participating in Ph.D. Programs, ‘Tissue Engineering and Regenerative Medicine’ and ‘Cell & Developmental Biology’, Jefferson College of Graduate Studies, Thomas Jefferson University

Lectures by Invitation

2005    “Wnt/b-catenin signaling and chondrocyte function”, School of Dental Medicine, University of Pennsylvania, Philadelphia (October 19, 2005)

2006    “Wnts in joint formation and diseases”, the 24^th Annual Meeting of the Japanese Society for Bone and Mineral Research, Tokyo, Japan (July 6-8^th, 2006)

2007    “Wnt signaling in cartilage matrix remodeling”, The 20^th Annual Meeting of the Japanese Society of Cartilage Metabolism, Okayama, Japan (2-3^rd March 2007)

2007    “Wnt signaling in cartilage matrix remodeling”, Gordon Research Conferences (cartilage biology and pathology) Ventura, CA (4-9^th March 2007)

2010       “Wnt/b-catenin signaling in regulation of articular cartilage development and organization.”, Mie University, Mie, Japan (April 2010)

2012    “-catenin signaling and osteochondromas.”, Tohoku University, Sendai, Japan (March 2012)

2014    “Beta-catenin Signaling in Cartilage: Its Inactivation in Osteochondromas”, UConn Health Center,   New England Musculoskeletal Institute, Framington (September 23^rd, 2014)

2014   “From the research of cartilage derived anti-tumor factor to the research of cartilage tumor”, Okayama University, Faculty of Dentisrty, Okayama Japan (March 15, 2014)

2014    “b-catenin signaling and osteochondroma”,  Showa University, School of Dentistry, Tokyo, Japan

(March 14, 2014)

2015    “Wnt/b-catenin signaling in genesis and maintenance of articular cartilage.”, School of Medicine, New York University

2016    “Control of glucose metabolism for tendon repair” Drexel University, Philadelphia (October, 2017)

2017    “Wnt/b-catenin signaling in skeletal development” Tufts University, Boston, MA (April 18, 2017)

2017    “Lineage tracing of skeletal progenitors during postnatal growing of growth plate” Stem Cell Center Research Seminar, Universiry of Maryland, Baltimore (June 8, 2017)

2017    “Tendon and glucose metabolism” Connective Tissue Research Meeting, 2017, Mie, Japan (June 16, 2017)

Organizing Roles in Scientific Meetings

2007    Organization of the session ‘Wnt signaling and cartilage’, The 20^th Annual Meeting of the Japanese Society of Cartilage Metabolism, Okayama, Japan (2-3^rd March 2007)

2008    Organization of the workshop ‘Wnt signaling in Skeletal Development and Diseases, The 54^th Orthopaedic Research Society Annual Meeting San Francisco, CA (March 2^nd, 2008)

2013-2016       Organization of the local scientific seminar “Orthopaedic Research Club” at University of Pennsylvania

Generation of genetically modified mice.

Animal surgery and drug treatment

Histology (chemical staining, Immunohistochemistry, IF, In situ hybridization)

Lase capture micro-dissection

Gene expression analyses (PCR, RNAseq, Gene array)

Cell culture (isolation of primary cells, reporter assay)

Molecular biology (vector construction and gene transfer)

Equipments (exculde common equipments):

Laser capture microdissection system (Leica LMD7)

Keyence all-in-one microscope BZ-X700

Cryostat and regular microtomes

Imager In vitrogen iBright FL1000