About

Eileen M. Shore, Ph.D., is a Cali and Weldon Research Professor in FOP and Co-Director of the Center for Research in FOP and Related Disorders at the Department of Orthopaedic Surgery, University of Pennsylvania. Her research focuses on the genetic regulation of cell differentiation and tissue development, with a particular emphasis on human genetic diseases involving extra-skeletal bone formation, such as fibrodysplasia ossificans progressiva (FOP) and progressive osseous heteroplasia (POH). Dr. Shore's work involves investigating the cellular and molecular basis of dysregulated stem cell fates, bone tissue formation, and skeletal development, utilizing in vitro and in vivo models to understand mutation effects and develop therapeutic strategies. Her notable contributions include identifying the genetic causes of FOP and POH, elucidating the role of the BMP signaling pathway, and exploring how mutations in ACVR1 and GNAS lead to heterotopic ossification. Her research has advanced understanding of how these mutations alter cell differentiation, tissue stiffness, and immune interactions, and has contributed to the development of models for pre-clinical drug testing. Dr. Shore's work is characterized by a translational perspective, closely tied to clinical observation and patient care, and she collaborates with a multidisciplinary team to explore mechanisms and potential treatments for these rare disorders.

Research topics

• Medicine
• Biology
• Pathology
• Cell biology
• Genetics

Selected publications

• Fibrodysplasia ossificans progressiva

  Elsevier eBooks · 2026-01-01

  book-chapterSenior author
  PublisherDOI

• List of contributors

  Elsevier eBooks · 2026-01-01

  book-chapter
  PublisherDOI

• An inducible knock-in mouse model of fibrodysplasia ossificans progressiva shows spontaneous formation of heterotopic ossification

  JBMR Plus · 2025-07-29 · 2 citations

  articleOpen accessSenior author

  Abstract Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder caused by mutations in ACVR1, most commonly the R206H variant. These mutations lead to heterotopic ossification (HO) in soft tissues, such as muscles, tendons, and ligaments. While people with FOP appear healthy at birth, they progressively develop HO starting in childhood, resulting in severe disabilities. Heterotopic ossification can be triggered by injuries, flare-ups, or occur spontaneously, and currently, there are limited medical or surgical treatment options available. To address these challenges, we generated a novel inducible Acvr1R206H knock-in mouse model (C57BL/6 background) that accurately replicates both injury- and non-injury-induced (spontaneous) HO. This model was engineered using an inducible CreERT2 system to express the R206H mutation following Cre-mediated recombination. As expected, muscle injury in these mice resulted in the formation of HO via endochondral ossification, a process in which cartilage is converted into bone. When induced by doxycycline administration employing the rt;tetO-Cre system the same Acvr1ARC-R206H floxed allele also led to the development of similar HO upon muscle injury. Furthermore, we developed a protocol to induce non-injury-induced HO in these mice and determined that HO progresses more slowly in the absence of injury. This mouse model holds great potential as a valuable tool to explore cellular processes underlying disease progression and to serve as pre-clinical model to test the efficacy of therapeutic interventions aimed at preventing HO in FOP.

  PublisherDOI

• Medical guidelines for fibrodysplasia ossificans progressiva

  JBMR Plus · 2025-09-11 · 6 citations

  articleOpen access

  Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic condition characterized by congenital malformations of the great toes and progressive heterotopic ossification (HO) in specific anatomic patterns. Present management summarized here is focused on early diagnosis, assiduous avoidance of injury and iatrogenic harm, symptomatic amelioration of painful flare-ups, and optimization of residual function. Twenty-one members of the International Clinical Council on FOP (ICC) and seven consultants from 15 countries, chosen for their clinical expertise in FOP, developed this summary statement. Further advances in therapeutics will be based on rigorous clinical trials to assess novel and emerging treatment and prevention strategies. A detailed and updated exploration of the topics outlined in this brief perspective can be found in "The Medical Management of Fibrodysplasia Ossificans Progressiva: Current Treatment Considerations" which can be found on the International Clinical Council on FOP (ICC) website (www.iccfop.org).

  PublisherDOI

• Fibrodysplasia ossificans progressiva emerges from obscurity

  Trends in Molecular Medicine · 2024-09-21 · 13 citations

  review
  PublisherDOI

• Molecular Developmental Biology of Fibrodysplasia Ossificans Progressiva: Measuring the Giant by Its Toe

  Biomolecules · 2024-08-15 · 4 citations

  reviewOpen access

  When a genetic disease is characterized by the abnormal activation of normal molecular pathways and cellular events, it is illuminating to critically examine the places and times of these activities both in health and disease. Therefore, because heterotopic ossification (HO) in fibrodysplasia ossificans progressiva (FOP) is by far the disease’s most prominent symptom, attention is also directed toward the pathways and processes of bone formation during skeletal development. FOP is recognizable by effects of the causative mutation on skeletal development even before HO manifests, specifically in the malformation of the great toes. This signature skeletal phenotype is the most highly penetrant, but is only one among several skeletal abnormalities associated with FOP. Patients may present clinically with joint malformation and ankylosis, particularly in the cervical spine and costovertebral joints, as well as characteristic facial features and a litany of less common, non-skeletal symptoms, all stemming from missense mutations in the ACVR1 gene. In the same way that studying the genetic cause of HO advanced our understanding of HO initiation and progression, insight into the roles of ACVR1 signaling during tissue development, particularly in the musculoskeletal system, can be gained from examining altered skeletal development in individuals with FOP. This review will detail what is known about the molecular mechanisms of developmental phenotypes in FOP and the early role of ACVR1 in skeletal patterning and growth, as well as highlight how better understanding these processes may serve to advance patient care, assessments of patient outcomes, and the fields of bone and joint biology.

  PublisherOA PDFDOI

• Learning on a Limb: An outreach module to engage high school students in orthopaedics

  Journal of Orthopaedic Research® · 2024-11-07

  articleOpen access

  Orthopaedic researchers need new strategies for engaging underrepresented minority (URM) students. Our field has demonstrated noticeable gaps in racial, ethnic, and gender diversity, which inhibit our ability to innovate and combat the severe socioeconomic burden of musculoskeletal disorders. Towards this goal, we designed, implemented, and evaluated Learning on a Limb (LoaL), an orthopaedic research outreach module to teach URM high school students about orthopaedic research. During the 4-h module, students completed hands-on activities to learn how biomechanical testing, microcomputed tomography, cell culture, and histology are used in orthopaedic research. Over 3 years, we recruited 32 high school students from the Greater Philadelphia Area to participate in LoaL. Most participants identified as racial/ethnic or gender minorities in orthopaedic research. Using pre/post-tests, we found that students experienced significant learning gains of 51 percentage points from completing LoaL. In addition to teaching students about orthopaedic research, post-survey data demonstrated that participating in LoaL strongly influenced students' interest in orthopaedic research and scientific confidence. Several students acted on this interest by completing summer research experiences in the McKay Orthopaedic Research Laboratory at the University of Pennsylvania. LoaL instructors also benefited by having the opportunity to "pay it forward" to the next generation of students and build community within their department. Empowering institutions to host modules like LoaL would synergistically inspire URM high school students and strengthen community within orthopaedic departments to ultimately enhance orthopaedic research innovations.

  PublisherOA PDFDOI

• Matrix metalloproteinase-9 deficiency confers resilience in fibrodysplasia ossificans progressiva in a man and mice

  Journal of Bone and Mineral Research · 2024-02-16 · 15 citations

  articleOpen access

  Single case studies of extraordinary disease resilience may provide therapeutic insight into conditions for which no definitive treatments exist. An otherwise healthy 35-year-old man (patient-R) with the canonical pathogenic ACVR1R206H variant and the classic congenital great toe malformation of fibrodysplasia ossificans progressiva (FOP) had extreme paucity of post-natal heterotopic ossification (HO) and nearly normal mobility. We hypothesized that patient-R lacked a sufficient post-natal inflammatory trigger for HO. A plasma biomarker survey revealed a reduction in total matrix metalloproteinase-9 (MMP-9) compared to healthy controls and individuals with quiescent FOP. Whole exome sequencing identified compound heterozygous variants in MMP-9 (c.59C > T, p.A20V and c.493G > A, p.D165N). Structural analysis of the D165N variant predicted both decreased MMP-9 secretion and activity that were confirmed by enzyme-linked immunosorbent assay and gelatin zymography. Further, human proinflammatory M1-like macrophages expressing either MMP-9 variant produced significantly less Activin A, an obligate ligand for HO in FOP, compared to wildtype controls. Importantly, MMP-9 inhibition by genetic, biologic, or pharmacologic means in multiple FOP mouse models abrogated trauma-induced HO, sequestered Activin A in the extracellular matrix (ECM), and induced regeneration of injured skeletal muscle. Our data suggest that MMP-9 is a druggable node linking inflammation to HO, orchestrates an existential role in the pathogenesis of FOP, and illustrates that a single patient's clinical phenotype can reveal critical molecular mechanisms of disease that unveil novel treatment strategies.

  PublisherOA PDFDOI

• Cellular and Molecular Mechanisms of Heterotopic Ossification in Fibrodysplasia Ossificans Progressiva

  Biomedicines · 2024-04-02 · 18 citations

  reviewOpen accessCorresponding

  Fibrodysplasia ossificans progressiva (FOP) is a debilitating genetic disorder characterized by recurrent episodes of heterotopic ossification (HO) formation in muscles, tendons, and ligaments. FOP is caused by a missense mutation in the ACVR1 gene (activin A receptor type I), an important signaling receptor involved in endochondral ossification. The ACVR1R206H mutation induces increased downstream canonical SMAD-signaling and drives tissue-resident progenitor cells with osteogenic potential to participate in endochondral HO formation. In this article, we review aberrant ACVR1R206H signaling and the cells that give rise to HO in FOP. FOP mouse models and lineage tracing analyses have been used to provide strong evidence for tissue-resident mesenchymal cells as cellular contributors to HO. We assess how the underlying mutation in FOP disrupts muscle-specific dynamics during homeostasis and repair, with a focus on muscle-resident mesenchymal cells known as fibro-adipogenic progenitors (FAPs). Accumulating research points to FAPs as a prominent HO progenitor population, with ACVR1R206H FAPs not only aberrantly differentiating into chondro-osteogenic lineages but creating a permissive environment for bone formation at the expense of muscle regeneration. We will further discuss the emerging role of ACVR1R206H FAPs in muscle regeneration and therapeutic targeting of these cells to reduce HO formation in FOP.

  PublisherOA PDFDOI

• Learning on a Limb: An outreach module to engage high school students in orthopaedics

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-09-18

  preprintOpen access

  Orthopaedic researchers need new strategies for engaging diverse students. Our field has demonstrated noticeable gaps in racial, ethnic, and gender diversity, which inhibit our ability to innovate and combat the severe socioeconomic burden of musculoskeletal disorders. Towards this goal, we designed, implemented, and evaluated Learning on a Limb, an orthopaedic research outreach module to teach diverse high school students about orthopaedic research. During the 4-hr module, students completed hands-on activities to learn how biomechanical testing, microcomputed tomography, cell culture, and histology are used in orthopaedic research. Over three years, we recruited 32 high school students from the Greater Philadelphia Area to participate in Learning on a Limb. Most participants identified as racial/ethnic or gender minorities in orthopaedic research. Using pre/post-tests, we found that students experienced significant learning gains of 51 percentage points from completing Learning on a Limb. In addition to teaching students about orthopaedic research, post-survey data demonstrated that participating in Learning on a Limb strongly influenced students' interest in orthopaedic research. Several students acted on this interest by completing summer research experiences in the McKay Orthopaedic Research Laboratory at the University of Pennsylvania. Learning on a Limb instructors also benefited by having the opportunity to "pay it forward" to the next generation of students and build community within their department. Empowering institutions to host modules like Learning on a Limb would synergistically inspire diverse high school students and strengthen community within orthopaedic departments to ultimately enhance orthopaedic research innovations.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01AR04191615S1

  NIH · $155k · 2015

• NIH Grant R01AR041916

  NIH · $5.3M · 2016

• NIH Grant R01AR046831

  NIH · $4.3M · 2017

• Mechanobiology of Progenitor Cells in Heterotopic Ossification

  NIH · $1.6M · 2018–2024

Frequent coauthors

• Frederick S. Kaplan

  University of Pennsylvania

  351 shared

• Michael Zasloff

  MedStar Heart & Vascular Institute

  147 shared

• Francis H. Gannon

  Baylor College of Medicine

  87 shared

• Robert J. Pignolo

  Mayo Clinic

  66 shared

• Jay C. Groppe

  37 shared

• Maximilian Muenke

  National Human Genome Research Institute

  36 shared

• Elizabeth A. Olmsted‐Davis

  Temple University

  35 shared

• Warren B. Bilker

  University of Pennsylvania

  34 shared

Labs

• Eileen M. Shore LabPI