Perelman School of Medicine at the University of Pennsylvania

McKay Orthopaedic Research Laboratory

Faculty

Eiki Koyama

faculty photo
Research Associate Professor of Orthopaedic Surgery
Department: Orthopaedic Surgery

Contact information
The Children's Hospital of Philadelphia
Translational Research Program in Pediatric Orthopaedics
Division of Orthopaedic Surgery
Department of Surgery
3615 Civic Center Boulevard
Abramson Research Center 910B
Philadelphia, PA 19104
Office: 267-425-2074
Fax: 267-426-2215
Education:
D.D.S. (Dentistry)
Matsumoto Dental University, 1985.
PhD (Developmental Biology)
Okayama University, 1992.
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Description of Research Expertise

I have been a biomedical researcher for more than 20 years and currently am a faculty member in the Translational Research Program in Pediatric Orthopedics at The Children's Hospital of Philadelphia. My research interest involves early limb patterning, craniofacial development and synovial joint formation.

In the early 1990s, my colleagues and I studied the roles of retinoic acid (RA) in early limb development. At that time, RA was thought to be one of the strong candidates of morphogen, which can determine the anteroposterior axis of developing limb buds. We have tackled this notion and found that RA is unlikely a morphogen, but it acts as an inducer of the morphogen to control the limb patterning. This notion has been widely accepted and has lead to the finding of the real morphogen, Hedgehog, which can be induced by RA.

I've started to study the mechanisms of synovial joint. At prospective joint sites, the first overt sign of joint development is the appearance of a layer of closely-packed mesenchymal non-chondrogenic cells referred to as interzone. The cells have been thought to be very important for joint formation, but its real function was obscure at that time. To tackle this key issue, my team and I carried out genetic cell tagging and tracking studies. We found that interzone cells gave rise to most of all joint tissues, including articular cartilage layers, synovial lining, inner capsule and intra-joint ligaments and clarified at the molecular level the interzone cells represent a specialized cohort of progenitor cells exclusively determined for joint formation. This study has shed light on the mechanisms of synovial joint formation and the work has been highly quoted by other biomedical researchers.More recently, I has joined forces with Dr. Hyun-Duck Nah, a faculty member in the CHOP Division of Plastic and reconstructive Surgery, to understand the development and growth of the temporomandibular joint and identify possible therapeutic means to treat TMJ osteoarthritis, a condition particularly common in women. The data and insights stemming from all the above research lines have generated publications in top peer-reviewed journals.

Currently I am focusing on several congenital conditions including Hereditary Multiple Exostoses (HME) that affects children and young adults. Based on our extensive knowledge of the normal processes of skeletal development and growth, I would like to clarify the molecular mechanisms of HME formation and growth. We hypothesized that the Heparan sulfate deficiency in HME causes mis-distribution and mis-expression of potent growth factors, such as Hedgehog protein and other pro-chondrogenic factors and enhances the responsiveness of perichondrial cells to these and other local factor. To verify this hypothesis, we have currently exploited a number of mouse models for HME. We expect that these powerful and unique models will also allow us to test possible rational pharmacologic therapies based on those insights.

Selected Publications

Till E. Bechtold1, Cheri Saunders1, Naito Kurio2, Paul C. Billings1, Maurizio Pacifici1, Hyun-Duck Nah2 and Eiki Koyama1: TMJ degenerative changes in Prg4-null mice are associated with ectopic hedgehog signaling. International Association for Dental Research/American Association for Dental Research in Republic of Korea June 2016.

Mundy C, Bello A, Sgariglia F, Koyama E, Pacifici M : HhAntag, a Hedgehog Signaling Antagonist, Suppresses Chondrogenesis and Modulates Canonical and Non-Canonical BMP Signaling. Journal of Cellular Physiology 231(5): 1033-1044, May 2016.

Decker, R.S., H. Um, N. Dyment, E. Koyama, M. Kronenberg, P. Maye, D. Rowe and M. Pacifici: Specific synovial joint progenitor cell populations uniquely contribute to articular cartilage growth and repair. Osteoarthritis Research Society International World Congress, Amsterdam, Netherlands April 2016.

TE. Bechtold, C. Saunders, RS. Decker, Um. HB, N. Cottingham, I. Salhab, N. Kurio, PC. Billings, M. Pacifici, HD. Nah, E. Koyama: Osteophyte formation and matrix mineralization in a TMJ osteoarthritis mouse model are associated with ectopic hedgehog signaling. Matrix Biology 52-54: 339-354, March 2016.

TE. Bechtold, C. Saunders, C. Mundy, Um. HB, RS. Decker, I. Salhab, N. Kurio, PC. Billings, M. Pacifici, HD. Nah, E. Koyama: Excess BMP Signaling in Heterotopic Cartilage Forming in Prg4-null TMJ Discs. Journal of Dental Research 95(3): 292-301, March 2016.

Usami, Y., A, .T. Gunawardena, E. Koyama, R.S. Decker, M. Pacifici and M. Enomoto-Iwamoto: Contributions Of Wnt/β-catenin-responsive Cells to Articular and Growth Plate Cartilage Growth. Annual Meeting of The Orthopaedic Research Society, Orlando, FL. March 2016.

Decker RS, Koyama E, Pacifici M : Articular Cartilage: Structural and Developmental Intricacies and Questions. Current Osteoporosis Reports December 2015.

Federica Sgariglia, Paul Billings, Hyo-Bin Um, Kevin Jones, Eiki Koyama, Maurizio Pacifici: Cranial base defects in a mouse model of Hereditary Multiple Exostoses are associated with ectopic hedgehog signaling. The American Society for Bone and Mineral Research. Washington State Convention Center October 2015.

Huegel J, Enomoto-Iwamoto M, Sgariglia F, Koyama E, Pacifici M: Heparanase stimulates chondrogenesis and is up-regulated in human ectopic cartilage: a mechanism possibly involved in hereditary multiple exostoses. American Journal of Pathology 185(6): 1676, June 2015.

T. Shimo, E. Koyama, N. Kurio, K. Matsumoto, T. Okui, S. Ibaragi, N. Yoshioka, A. Sasaki : Expression and roles of CCN2 in dental epithelial cells. In Vivo 29(2): 189-195, March 2015.

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Last updated: 08/31/2016
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