Description of Research Expertise

I have been a biomedical researcher for more than 25 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 craniofacial development, synovial joint formation and molecular mechanism /treatment of congenital disease.

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 my colleagues and I are investigating 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, we aim to clarify the molecular mechanisms of ectopic cartilage formation and growth using HME mouse models. We discovered that (1) 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 (2) enhances the responsiveness of progenitor cells to these and other local factors. We have currently exploited a number of mouse models for HME and test if blockage of these signaling could prevent skeletal tumor development.

Selected Publications

A A;amazi, P. Chandrasekaran, B. Kwok, C. Wang, D.B. Frank, D.E. Birk, R.L. Mauck, N. A. Dyment, E. Koyama, L. Han.: Type V collagen regulates the progenitor cell fate and matrix establishment in TMJ condylar cartilage JMES : 2022.

Minwook Kim, Eiki Koyama, Cheri M Saunders, William Querido, Nancy Pleshko, and Maurizio Pacifici: Synovial joint cavitation initiates with microcavities in interzone and is coupled to skeletal flexion and elongation in developing mouse embryo limbs Biology Open : 2022.

Prashant Chandrasekaran1, Abdulaziz Alanazi1, Bryan Kwok1, Robert L. Mauck2, Nathaniel A. Dyment2, Eiki Koyama3, Lin Han1: Distinct Activities of Type V Collagen in TMJ Articular Disc versus Condylar Cartilage during Joint Growth and Remodeling TMJ Bioengineering Conference – 7 : 2022.

Mary K. Evans (1), Tonia K. Tsinman (1), Xi Jiang (1), Ellie J. Ferguson (1), Joel Boerckel (1), Lin Han (2), Eiki Koyama (3), Robert L. Mauck (1), Nathaniel A. Dyment (1): NON-MUSCLE MYOSINS ARE CRITICAL REGULATORS OF SKELETAL AND CONNECTIVE TISSUE FORMATION Summer Biomechanics, Bioengineering and Biotransport Conference : 2022.

Mundy C, Chung J, Koyama E, Bunting S, Mahimkar R, Pacifici M: Osteochondroma formation is independent of heparanase expression as revealed in a mouse model of hereditary multiple exostoses. J Orthop Res : 2022.

Rux D, Helbig K, Han B, Cortese C, Koyama E, Han L, Pacifici M: Primary Cilia Direct Murine Articular Cartilage Tidemark Patterning Through Hedgehog Signaling and Ambulatory Load J Bone Miner Res : 2022.

Xinhua Li, Shuting Yang, Zahra Chinipardaz, Eiki Koyama, and Shuying Yang: SAG therapy restores bone growth and reduces enchondroma incidence in a model of skeletal chondrodysplasia caused by Ihh deficiency Molecular Therapy: Methods & Clinical Development 23 : 2021.

Danielle Rux, Kimberly Helbig, Eiki Koyama, MaurizioPacifici: Hox11 expression characterizes developing zeugopod synovial joints and is coupled to postnatal articular cartilage morphogenesis into functional zones in mice Developmental Biology 477 : 49-63,2021.

Xinhua Li; Shuting Yang; Zahra Chinipardaz; Eiki Koyama; Shuying Yang: SAG therapy restores bone growth and reduces enchondroma incidence in a model of skeletal chondrodysplasias caused by Ihh deficiency Molecular Therapy-Methods & Clinical Development 1 (23): 461-475,2021.

Tonia K Tsinman, Xi Jiang, Lin Han, Eiki Koyama, Robert L Mauck, Nathaniel A Dyment: Intrinsic and growth-mediated cell and matrix specialization during murine meniscus tissue assembly FASEB J. 35 (8): e21779,2021.

Academic 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
Phone: 267-425-2074