Research Topics
Species | EILEEN SHORESummaryAffiliation: University of Pennsylvania Country: USA Publications
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Publications
Fibrodysplasia ossificans progressiva: clinical and genetic aspectsRobert 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...- Role of altered signal transduction in heterotopic ossification and fibrodysplasia ossificans progressivaEileen 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.... - Inherited human diseases of heterotopic bone formationEileen 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.... - 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... 
Paternally inherited inactivating mutations of the GNAS1 gene in progressive osseous heteroplasiaEileen 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...- A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressivaEileen 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... - Classic and atypical fibrodysplasia ossificans progressiva (FOP) phenotypes are caused by mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1Frederick 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... - Paresis of a bone morphogenetic protein-antagonist response in a genetic disorder of heterotopic skeletogenesisJaimo Ahn
University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
J Bone Joint Surg Am 85:667-74. 2003..This paresis may account in part for the increased BMP-4 activity in fibrodysplasia ossificans progressiva... - Early mortality and cardiorespiratory failure in patients with fibrodysplasia ossificans progressivaFrederick 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... - 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... - Morphogen receptor genes and metamorphogenes: skeleton keys to metamorphosisFrederick 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... - Fibrodysplasia ossificans progressivaFrederick 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... - Early diagnosis of fibrodysplasia ossificans progressivaFrederick 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... - A new era for fibrodysplasia ossificans progressiva: a druggable target for the second skeletonFrederick 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... 
High-throughput screening for modulators of mesenchymal stem cell chondrogenesisALICE 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...- Circulating osteogenic precursor cellsRobert 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... - Hematopoietic stem-cell contribution to ectopic skeletogenesisFrederick 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... - 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.... - Dysregulation of the BMP-4 signaling pathway in fibrodysplasia ossificans progressivaFrederick 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... - In vivo somatic cell gene transfer of an engineered Noggin mutein prevents BMP4-induced heterotopic ossificationDavid 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... - Identification of progenitor cells that contribute to heterotopic skeletogenesisVitali 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... - Circulating osteogenic precursor cells in heterotopic bone formationRobin 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... - The FOP metamorphogene encodes a novel type I receptor that dysregulates BMP signalingFrederick 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.... - Heterotopic ossificationFrederick 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... - The fibrodysplasia ossificans progressiva R206H ACVR1 mutation activates BMP-independent chondrogenesis and zebrafish embryo ventralizationQi Shen
Department of Orthopaedic Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104 6081, USA
J Clin Invest 119:3462-72. 2009.... - HSPG modulation of BMP signaling in fibrodysplasia ossificans progressiva cellsMichael 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... - Over-expression of BMP4 and BMP5 in a child with axial skeletal malformations and heterotopic ossification: a new syndromeGeorge 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... - Lumbar puncture and surgical intervention in a child with undiagnosed fibrodysplasia ossificans progressivaKareem A Zaghloul
Division of Neurosurgery, Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
J Neurosurg Pediatr 1:91-4. 2008.... - 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 pathwayAlyssa A Schaffer
Division of Orthopaedic Surgery, Children's Hospital of Philadelphia, Institution B, Philadelphia, PA, USA
Spine 30:1379-85. 2005..While the noggin gene (NOG) is not mutated in patients who have FOP, these findings extend a growing body of evidence implicating overactivity of the BMP signaling pathway in the molecular pathogenesis of FOP... - Fibrodysplasia ossificans progressiva (FOP), a disorder of ectopic osteogenesis, misregulates cell surface expression and trafficking of BMPRIALourdes 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.... - Focal fibronodular heterotopic ossification. A case reportHoward 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 - 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... - Heparan sulfate proteoglycans (HSPGs) modulate BMP2 osteogenic bioactivity in C2C12 cellsXiangyang 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... - Proximal tibial osteochondromas in patients with fibrodysplasia ossificans progressivaGregory 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... - Reported noggin mutations are PCR errorsMei-qi Xu
Am J Med Genet 109:161; author reply 163-4. 2002 - Functional modeling of the ACVR1 (R206H) mutation in FOPJay 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.... - 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.... - Progressive osseous heteroplasia in the face of a childRussell 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... - Progressive osseous heteroplasia-like heterotopic ossification in a male infant with pseudohypoparathyroidism type Ia: a case reportInessa 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..Our patient has evidence of both severe POH and PHP Ia, apparently due to a de novo mutation in GNAS...
Research Grants
- MOLECULAR GENETICS OF PROGRESSIVE OSSEOUS HETEROPLASIAEILEEN 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. ..
- MOLECULAR GENETICS OF PROGRESSIVE OSSEOUS HETEROPLASIAEILEEN 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. ..