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Motomi Enomoto-Iwamoto, DDS, PhD

Academic Title:

Professor

Primary Appointment:

Orthopaedics

Additional Title:

Associate Professor

Location:

20 Penn St. HSFII-S022

Phone (Primary):

410-706-4767

Education and Training

1983              D.D.S, Osaka University (Japan)

1987              Ph.D.,  Osaka University (Biochemistry)

1987-1988     Postdoctoral Fellow, Osaka University, Osaka Japan

1989-1992     Postdoctoral Fellow, Department of Microbiology, School of Medicine, University of Pennsylvania

Biosketch

Dr. Enomoto-Iwamoto is a leading cartilage biologist. Her research focuses on (1) mechanisms of endochondral ossification and articular cartilage development and organization and (2) pathogenesis of cartilage tumor and synovial joint disorders such as osteoarthritis.

Dr. Enomoto-Iwamoto has conducted some of the pioneer works that discover importance of Wnt/b-catenin signaling in control of cartilage formation, growth and function. She has demonstrated that activation of this signaling is associated with progression of degenerative joint diseases and that loss and excess activation of this signaling in cartilage causes skeletal deformity. These pioneering studies are followed by a large amount of research on this signaling in the basic, translational and clinical orthopaedic research fields. More recently, her laboratory explored importance of local progenitors in tendon healing.  She has studied to develop the therapeutic drugs and concepts that make the local tendon progenitors to proceed toward a correct path and inhibit their trans-differentiation into incorrect lineages, leading to stimulation of tendon repair. 

Research/Clinical Keywords

cartilage, growth plate, tendon, articular cartilage, cartilage tumor, tendon injury, mesenchymal stem/progenitors, Wnt/beta-catenin signaling

Highlighted Publications

Tendon Mineralization Is Progressive and Associated with Deterioration of Tendon Biomechanical Properties, and Requires BMP-Smad Signaling in the Mouse Achilles Tendon Injury Model. Zhang K, Asai S, Hast MW, Liu M, Usami Y, Iwamoto M, Soslowsky LJ, Enomoto-Iwamoto M. Matrix Biol. 2016 52-54:315-24. PMID:26825318, NIHMSID 756672

Tendon Progenitor cells in injured tendons have a strong chondrogenic potential: The CD105-negative subpopulation induces chondrogenic degeneration. Asai S, Otsuru S, Cahdela ME, Cantely L, Uchibe K, Hofmann TJ, Zhang K, Wapner KL, Soslwosky L, Horwitz EM and Enomoto-Iwamoto M Setm Cells 2014 Dec;32(12):3266-77. doi: 10.1002/stem.1847. PMID: 25220576, PMCID: PMC4245375

Loss of b-Catenin Induces Multifocal Periosteal Chondroma-Like Masses in Mice. Cantley L, Saunders C, Guttenberg M, Candela ME, Ohta Y, Yasuhara R, Kondo N, Sgariglia F, Asai S, Zhang X, Qin L, Hecht JT, Chen D, Yamamoto M, Toyosawa S, Dormans JP, Esko JD, Yamaguchi Y, Iwamoto M, Pacifici M, Enomoto-Iwamoto M. Am J Pathol. 2013 Mar;182(3):917-27. PMID: 23274133 

Roles of β-catenin signaling in phenotypic expression and proliferation of articular cartilage superficial zone cells. Yasuhara R, Ohta Y, Yuasa T, Kondo N, Hoang T, Addya S, Fortina P, Pacifici M, Iwamoto M, Enomoto-Iwamoto M. Lab Invest. 2011 Dec;91(12):1739-52. PMID: 21968810. 

Transient Activation of Wnt/b-catenin Signaling Induces Abnormal Growth Plate Closure and Articular Cartilage Thickening in Postnatal Mice.Yuasa, T., Kondo, N., Yasuhara, R., Shimono, K., Mackem, S., Pacifici, M., Iwamoto, M., Enomoto-Iwamoto, M.  Am. J. Pathol. (2009) 175, 1993-2003. PMID:PMC2774063

Additional Publication Citations

URL, http://www.ncbi.nlm.nih.gov/sites/myncbi/motomi.enomotoiwamoto.1/bibliography/46009278/public/?sort=date&direction=ascending

Research Interests

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.

Awards and Affiliations

1998  Investigator award from Japanese Society for Cartilage Metabolism

1998  Yumikura award from Society of Osaka University Faculty of Dentistry

Grants and Contracts

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

Professional Activity

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 24th Annual Meeting of the Japanese Society for Bone and Mineral Research, Tokyo, Japan (July 6-8th, 2006)

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

2007    “Wnt signaling in cartilage matrix remodeling”, Gordon Research Conferences (cartilage biology and pathology) Ventura, CA (4-9th 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 23rd, 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 20th Annual Meeting of the Japanese Society of Cartilage Metabolism, Okayama, Japan (2-3rd March 2007)

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

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

Lab Techniques

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