EILEEN SHORE

Summary

Affiliation: University of Pennsylvania
Country: USA

Publications

  1. pmc Fibrodysplasia ossificans progressiva: a human genetic disorder of extraskeletal bone formation, or--how does one tissue become another?
    Eileen M Shore
    Department of Orthopedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
    Wiley Interdiscip Rev Dev Biol 1:153-65. 2012
  2. pmc Fibrodysplasia ossificans progressiva: clinical and genetic aspects
    Robert J Pignolo
    Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Orphanet J Rare Dis 6:80. 2011
  3. pmc Role of altered signal transduction in heterotopic ossification and fibrodysplasia ossificans progressiva
    Eileen M Shore
    Department of Orthopaedic Surgery, University of Pennsylvania School of Medicine, 426 Stemmler Hall, 3450 Hamilton Walk, Philadelphia, PA 19104 6081, USA
    Curr Osteoporos Rep 9:83-8. 2011
  4. pmc Inherited human diseases of heterotopic bone formation
    Eileen M Shore
    Department of Orthopedic Surgery, University of Pennsylvania School of Medicine, 424 Stemmler Hall, 3450 Hamilton Walk, Philadelphia, PA 19104 6081, USA
    Nat Rev Rheumatol 6:518-27. 2010
  5. pmc Insights from a rare genetic disorder of extra-skeletal bone formation, fibrodysplasia ossificans progressiva (FOP)
    Eileen M Shore
    Department of Orthopaedic Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Bone 43:427-33. 2008
  6. ncbi Paternally inherited inactivating mutations of the GNAS1 gene in progressive osseous heteroplasia
    Eileen M Shore
    Department of Orthopaedic Surgery, University of Pennsylvania School of Medicine, Philadelphia 19104 6018, USA
    N Engl J Med 346:99-106. 2002
  7. ncbi A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva
    Eileen M Shore
    Center for Research in FOP and Related Disorders, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Nat Genet 38:525-7. 2006
  8. ncbi Paresis of a bone morphogenetic protein-antagonist response in a genetic disorder of heterotopic skeletogenesis
    Jaimo Ahn
    University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    J Bone Joint Surg Am 85:667-74. 2003
  9. pmc Classic and atypical fibrodysplasia ossificans progressiva (FOP) phenotypes are caused by mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1
    Frederick S Kaplan
    Department of Orthopaedic Surgery, University Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6081, USA
    Hum Mutat 30:379-90. 2009
  10. ncbi Morphogen receptor genes and metamorphogenes: skeleton keys to metamorphosis
    Frederick S Kaplan
    Department of Orthopaedic Surgery and Medicine, The University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Ann N Y Acad Sci 1116:113-33. 2007

Research Grants

Collaborators

Detail Information

Publications40

  1. pmc Fibrodysplasia ossificans progressiva: a human genetic disorder of extraskeletal bone formation, or--how does one tissue become another?
    Eileen M Shore
    Department of Orthopedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
    Wiley Interdiscip Rev Dev Biol 1:153-65. 2012
    ....
  2. pmc Fibrodysplasia ossificans progressiva: clinical and genetic aspects
    Robert J Pignolo
    Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Orphanet J Rare Dis 6:80. 2011
    ..The median lifespan is approximately 40 years of age. Most patients are wheelchair-bound by the end of the second decade of life and commonly die of complications of thoracic insufficiency syndrome...
  3. pmc Role of altered signal transduction in heterotopic ossification and fibrodysplasia ossificans progressiva
    Eileen M Shore
    Department of Orthopaedic Surgery, University of Pennsylvania School of Medicine, 426 Stemmler Hall, 3450 Hamilton Walk, Philadelphia, PA 19104 6081, USA
    Curr Osteoporos Rep 9:83-8. 2011
    ....
  4. pmc Inherited human diseases of heterotopic bone formation
    Eileen M Shore
    Department of Orthopedic Surgery, University of Pennsylvania School of Medicine, 424 Stemmler Hall, 3450 Hamilton Walk, Philadelphia, PA 19104 6081, USA
    Nat Rev Rheumatol 6:518-27. 2010
    ....
  5. pmc Insights from a rare genetic disorder of extra-skeletal bone formation, fibrodysplasia ossificans progressiva (FOP)
    Eileen M Shore
    Department of Orthopaedic Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Bone 43:427-33. 2008
    ..This review will illustrate some of the many insights that we have gained by studying FOP...
  6. ncbi Paternally inherited inactivating mutations of the GNAS1 gene in progressive osseous heteroplasia
    Eileen M Shore
    Department of Orthopaedic Surgery, University of Pennsylvania School of Medicine, Philadelphia 19104 6018, USA
    N Engl J Med 346:99-106. 2002
    ..AHO is caused by heterozygous inactivating mutations in the GNAS1 gene that result in decreased expression or function of the alpha subunit of the stimulatory G protein (Gsalpha) of adenylyl cyclase...
  7. ncbi A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva
    Eileen M Shore
    Center for Research in FOP and Related Disorders, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Nat Genet 38:525-7. 2006
    ..Protein modeling predicts destabilization of the GS domain, consistent with constitutive activation of ACVR1 as the underlying cause of the ectopic chondrogenesis, osteogenesis and joint fusions seen in FOP...
  8. ncbi Paresis of a bone morphogenetic protein-antagonist response in a genetic disorder of heterotopic skeletogenesis
    Jaimo Ahn
    University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    J Bone Joint Surg Am 85:667-74. 2003
    ..Therefore, a defect in the feedback pathway between BMP-4 and one or more of its extracellular antagonists could contribute to the elevated BMP-4 activity characteristic of fibrodysplasia ossificans progressiva...
  9. pmc Classic and atypical fibrodysplasia ossificans progressiva (FOP) phenotypes are caused by mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1
    Frederick S Kaplan
    Department of Orthopaedic Surgery, University Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6081, USA
    Hum Mutat 30:379-90. 2009
    ..We observed genotype-phenotype correlation between some ACVR1 mutations and the age of onset of heterotopic ossification or on embryonic skeletal development...
  10. ncbi Morphogen receptor genes and metamorphogenes: skeleton keys to metamorphosis
    Frederick S Kaplan
    Department of Orthopaedic Surgery and Medicine, The University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Ann N Y Acad Sci 1116:113-33. 2007
    ..Such insight is applicable to a broad range of human afflictions...
  11. pmc Fibrodysplasia ossificans progressiva
    Frederick S Kaplan
    Departments of Orthopedic Surgery and Medicine, The University of Pennsylvania School of Medicine, c o Hospital of The University of Pennsylvania, Philadelphia, PA, USA
    Best Pract Res Clin Rheumatol 22:191-205. 2008
    ..Effective therapies for FOP, and possibly for other common conditions of HO, may potentially be based on future interventions that block ACVR1/ALK2 signalling...
  12. pmc Early diagnosis of fibrodysplasia ossificans progressiva
    Frederick S Kaplan
    Center for Research in FOP and Related Disorders, and Department of Orthopaedic Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    Pediatrics 121:e1295-300. 2008
    ..Recently, the genetic cause of fibrodysplasia ossificans progressiva was identified, and definitive genetic testing for fibrodysplasia ossificans progressiva is now available before the appearance of heterotopic ossification...
  13. doi High-throughput screening for modulators of mesenchymal stem cell chondrogenesis
    ALICE H HUANG
    McKay Orthopaedic Research Laboratory, Department of Orthopaedic Surgery, University of Pennsylvania, 36th Street and Hamilton Walk, Philadelphia, PA 19104, USA
    Ann Biomed Eng 36:1909-21. 2008
    ..These studies demonstrate our ability to carry out high-throughput screening assays for modulators of chondrogenesis...
  14. pmc Skeletal metamorphosis in fibrodysplasia ossificans progressiva (FOP)
    Frederick S Kaplan
    Departments of Orthopaedic Surgery and Medicine, c o Department of Orthopaedic Surgery, Hospital of the University of Pennsylvania, Silverstein 2, 3400 Spruce Street, Philadelphia, PA, 19104, USA
    J Bone Miner Metab 26:521-30. 2008
    ....
  15. pmc Identification of progenitor cells that contribute to heterotopic skeletogenesis
    Vitali Y Lounev
    Department of Orthopaedic Surgery, University of Pennsylvania School of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA
    J Bone Joint Surg Am 91:652-63. 2009
    ..An understanding of the cellular basis of heterotopic ossification will aid in the development of targeted, cell-specific therapies for the treatment and prevention of heterotopic ossification...
  16. pmc Circulating osteogenic precursor cells in heterotopic bone formation
    Robin K Suda
    Department of Medicine, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania 19104 6160, USA
    Stem Cells 27:2209-19. 2009
    ..Thus, bone formation is not limited to cells of the mesenchymal lineage, and circulating cells of hematopoietic origin can also serve as osteogenic precursors at remote sites of tissue inflammation...
  17. pmc The FOP metamorphogene encodes a novel type I receptor that dysregulates BMP signaling
    Frederick S Kaplan
    Department of Orthopaedic Surgery, The Center for Research in FOP and Related Disorders, The University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Cytokine Growth Factor Rev 20:399-407. 2009
    ....
  18. pmc Early mortality and cardiorespiratory failure in patients with fibrodysplasia ossificans progressiva
    Frederick S Kaplan
    Department of Orthopaedic Surgery, Hospital of the University of Pennsylvania, Silverstein 2, 3400 Spruce Street, Philadelphia, PA 19104, USA
    J Bone Joint Surg Am 92:686-91. 2010
    ..However, little is known about the lifespan or causes of mortality in these patients. We undertook this study to determine the lifespan and causes of mortality in individuals who had fibrodysplasia ossificans progressiva...
  19. pmc Circulating osteogenic precursor cells
    Robert J Pignolo
    Department of Medicine, University of Pennsylvania, School of Medicine, Philadelphia, PA 19104 6081, USA
    Crit Rev Eukaryot Gene Expr 20:171-80. 2010
    ..The role of COP cells in physiologic and pathophysiologic conditions of de novo bone formation suggests that they may serve as future targets for diagnostic measurements and therapeutic interventions...
  20. pmc Dysregulated BMP signaling and enhanced osteogenic differentiation of connective tissue progenitor cells from patients with fibrodysplasia ossificans progressiva (FOP)
    Paul C Billings
    The Center for Research in FOP and Related Disorders, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Bone Miner Res 23:305-13. 2008
    ..We isolated such cells from discarded primary teeth of patients with FOP and controls and discovered dysregulation of BMP signaling and rapid osteoblast differentiation in FOP cells compared with control cells...
  21. ncbi In vivo somatic cell gene transfer of an engineered Noggin mutein prevents BMP4-induced heterotopic ossification
    David L Glaser
    Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA
    J Bone Joint Surg Am 85:2332-42. 2003
    ..Therefore, we hypothesized that engineering more effective inhibitors of this BMP-signaling process may lead to the development of therapies for such conditions...
  22. ncbi Hematopoietic stem-cell contribution to ectopic skeletogenesis
    Frederick S Kaplan
    Center for Research in Fibrodyplasia Ossificans Progressiva and Related Disorders, Department of Orthopaedic Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6081, USA
    J Bone Joint Surg Am 89:347-57. 2007
    ..However, the definitive contribution of hematopoietic cells to the pathogenesis of ectopic skeletogenesis remains obscure...
  23. ncbi Dysregulation of the BMP-4 signaling pathway in fibrodysplasia ossificans progressiva
    Frederick S Kaplan
    University of Pennsylvania School of Medicine, Department of Orthopaedic Surgery, Silverstein Two, 3400 Spruce Street, Philadelphia, PA 19104, USA
    Ann N Y Acad Sci 1068:54-65. 2006
    ..Signaling pathways that fit these criteria are the BMP signaling pathway and its interacting pathways. A large body of data suggest that the BMP-4 signaling pathway is dysregulated in FOP...
  24. ncbi A new era for fibrodysplasia ossificans progressiva: a druggable target for the second skeleton
    Frederick S Kaplan
    University of Pennsylvania School of Medicine, Department of Orthopaedic Surgery, Hospital of the University of Pennsylvania, Silverstein Two, 34th and Spruce Street, Philadelphia, PA 19104, USA
    Expert Opin Biol Ther 7:705-12. 2007
    ..Effective therapies for FOP, and possibly for a vast array of more common conditions of heterotopic ossification, will be based on blocking activin-like kinase-2, a critical node in the BMP signaling pathway...
  25. ncbi Heterotopic ossification
    Frederick S Kaplan
    Departments of Orthopaedic Surgery and Medicine, The University of Pennsylvania School of Medicine, Silverstein 2, 3400 Spruce Street, Philadelphia, PA 19104 5283, USA
    J Am Acad Orthop Surg 12:116-25. 2004
    ..Better understanding of the complex developmental and molecular pathology of these disorders may lead to more effective strategies to prevent and treat other, more common forms of heterotopic ossification...
  26. pmc The fibrodysplasia ossificans progressiva R206H ACVR1 mutation activates BMP-independent chondrogenesis and zebrafish embryo ventralization
    Qi Shen
    Department of Orthopaedic Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6081, USA
    J Clin Invest 119:3462-72. 2009
    ....
  27. ncbi Developmental anomalies of the cervical spine in patients with fibrodysplasia ossificans progressiva are distinctly different from those in patients with Klippel-Feil syndrome: clues from the BMP signaling pathway
    Alyssa A Schaffer
    Division of Orthopaedic Surgery, Children s Hospital of Philadelphia, Institution B, Philadelphia, PA, USA
    Spine (Phila Pa 1976) 30:1379-85. 2005
    ..A radiographic analysis of the cervical spine of 70 patients diagnosed with fibrodysplasia ossificans progressiva (FOP) and 33 diagnosed with Klippel-Feil (KF) syndrome was conducted...
  28. ncbi Fibrodysplasia ossificans progressiva (FOP), a disorder of ectopic osteogenesis, misregulates cell surface expression and trafficking of BMPRIA
    Lourdes Serrano DE LA Peña
    Department of Orthopaedic Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6081, USA
    J Bone Miner Res 20:1168-76. 2005
    ....
  29. ncbi Over-expression of BMP4 and BMP5 in a child with axial skeletal malformations and heterotopic ossification: a new syndrome
    George J Feldman
    Department of Orthopaedic Surgery, Center for Research in FOP and Related Disorders, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Am J Med Genet A 143:699-706. 2007
    ..Our data suggest that dysregulated expression of BMP4 and BMP5 genes is associated with an array of human axial skeletal abnormalities similar to the short ear mouse and FOP...
  30. ncbi HSPG modulation of BMP signaling in fibrodysplasia ossificans progressiva cells
    Michael P O'Connell
    Department of Orthopaedic Surgery, The University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, 19104, USA
    J Cell Biochem 102:1493-503. 2007
    ..These data support that HSPG modulation of BMP signaling is altered in cells from patients with FOP and that altered HSPG-related BMP signaling may play a role in the pathogenesis of the disease...
  31. doi Lumbar puncture and surgical intervention in a child with undiagnosed fibrodysplasia ossificans progressiva
    Kareem A Zaghloul
    Division of Neurosurgery, Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    J Neurosurg Pediatr 1:91-4. 2008
    ....
  32. ncbi Dysregulation of the BMP-p38 MAPK signaling pathway in cells from patients with fibrodysplasia ossificans progressiva (FOP)
    Jennifer L Fiori
    Department of Orthopaedic Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6081, USA
    J Bone Miner Res 21:902-9. 2006
    ..FOP lymphocytes exhibit defects in the BMP-p38 MAPK pathway, suggesting that altered BMP signaling underlies ectopic bone formation in this disease...
  33. ncbi Heparan sulfate proteoglycans (HSPGs) modulate BMP2 osteogenic bioactivity in C2C12 cells
    Xiangyang Jiao
    Center For Research in Fibrodysplasia Ossificans Progressiva FOP and Related Disorders and the Department of Orthopaedics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 282:1080-6. 2007
    ..The addition of exogenous heparin, a widely used anticoagulant, reduced BMP2 signaling. Our results suggest that cell surface HSPGs mediate BMP2 internalization and modulate BMP2 osteogenic activity...
  34. ncbi Focal fibronodular heterotopic ossification. A case report
    Howard B Yeon
    Hand and Upper Extremity Service, Department of Orthopaedic Surgery, Massachusetts General Hospital, Yawkey Center, Suite 2100, 55 Fruit Street, Boston, MA 02114, USA
    J Bone Joint Surg Am 89:1329-36. 2007
  35. pmc Proximal tibial osteochondromas in patients with fibrodysplasia ossificans progressiva
    Gregory K Deirmengian
    Department of Orthopaedic Surgery, The University of Pennsylvania School of Medicine, Silverstein 2, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA
    J Bone Joint Surg Am 90:366-74. 2008
    ..The purpose of the present study was to determine the prevalence and characteristics of proximal tibial osteochondromas in individuals who have fibrodysplasia ossificans progressiva...
  36. ncbi Reported noggin mutations are PCR errors
    Mei qi Xu
    Am J Med Genet 109:161; author reply 163-4. 2002
  37. ncbi Functional modeling of the ACVR1 (R206H) mutation in FOP
    Jay C Groppe
    Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229 3900, USA
    Clin Orthop Relat Res 462:87-92. 2007
    ....
  38. ncbi Progressive osseous heteroplasia in the face of a child
    Russell A Faust
    Department of Otolaryngology and Pediatrics, Children s Hospital of Michigan, Detroit, 48201, USA
    Am J Med Genet A 118:71-5. 2003
    ..Analysis of DNA from peripheral blood leukocytes showed mutations in the gene encoding the alpha subunit of the stimulatory G protein of adenylyl cyclase (GNAS1), confirming the diagnosis of progressive osseous heteroplasia...
  39. ncbi Stromal cells of fibrodysplasia ossificans progressiva lesions express smooth muscle lineage markers and the osteogenic transcription factor Runx2/Cbfa-1: clues to a vascular origin of heterotopic ossification?
    Laszlo Hegyi
    Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, Cambridge, UK
    J Pathol 201:141-8. 2003
    ....
  40. ncbi Progressive osseous heteroplasia-like heterotopic ossification in a male infant with pseudohypoparathyroidism type Ia: a case report
    Inessa M Gelfand
    Department of Pediatrics, Division of Pediatric Endocrinology and Diabetology, Indiana University School of Medicine, James Whitcomb Riley Hospital for Children, Indianapolis, IN, USA
    Bone 40:1425-8. 2007
    ..Mutations that cause PHP Ia when maternally inherited can cause POH when paternally inherited. We present an unusual case of a boy with clinical features of both POH and PHP Ia, and a GNAS inactivating mutation...

Research Grants9

  1. MOLECULAR GENETICS OF PROGRESSIVE OSSEOUS HETEROPLASIA
    EILEEN SHORE; Fiscal Year: 2002
    ..Accomplishment of these Specific Aims will provide the foundation for future work that will examine the pathways through which GNAS1 expression leads to regulation of normal and ectopic bone formation. ..
  2. MOLECULAR GENETICS OF PROGRESSIVE OSSEOUS HETEROPLASIA
    EILEEN SHORE; Fiscal Year: 2009
    ..These investigations will provide important information for developing diagnostic and treatment strategies for a wide range of disorders of bone such as POH and more common conditions. ..