McKay Orthopaedic Research Laboratory

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McKay Orthopaedic Research Laboratory > Eileen M. Shore, Ph.D.

Eileen M. Shore, Ph.D.

Research Associate Professor of Orthopaedic Surgery
Research Associate Professor of Genetics

HOMETOWN


EDUCATION
Ph.D., Cell and Molecular Biology, University of Pennsylvania, 1987
M.A., Biology, Indiana University, 1978
B.S., Biology, University of Notre Dame, 1976

AREAS OF EXPERTISE
Genetic diseases of bone formation and development. Molecular biology and genetics of bone formation

AREAS OF SPECIAL INTEREST
Research in our laboratory is focused on genetic diseases of bone formation, mainly fibrodysplasia ossificans progressiva (FOP) and progressive osseous heteroplasia (POH). Both of these rare disorders are characterized by de novo formation of bone: in FOP, the ectopic bone forms in deep connective tissues such as muscle; and in POH, bone formation initiates within the skin. Our long term goals have been to identify the genetic causes of these conditions and the cellular pathways that are involved in the induction of bone development and formation, and to use this information to develop treatments for these and other disorders of bone. With the identification of the mutated genes for POH and FOP, our experimental directions are now focused on determining the functions of these genes and the consequences of the identified mutations. Additional project information can be found at: http://www.med.upenn.edu/camb/faculty/ggr/shore.html

RECENT PUBLICATIONS
  1. Serrano de la Pena, L., P.C. Billings, J.L. Fiori, F.S. Kaplan, E.M. Shore (2005) Fybrodysplasia ossificans progressiva (FOP), a disorder of ectopic osteogenesis, misregulates cell surface expression and trafficking of BMPRIA. J. Bone Min. Res. 20, 1168-1176.
  2. Schaffer, A.A., F.S. Kaplan, M.R. Tracy, M.L. O'Brien, J.P. Dormans, E.M. Shore, R.M. Harland, K. Kusumi (2005). Developmental anomalies of the cervical spine in patients with fibrodysplasia ossificans progressiva: clues from the BMP signaling pathway. Spine 30, 1379-1385.
  3. Hebela, N., E.M. Shore, and F.S. Kaplan (2005). Three pairs of monozygotic twins with fibrodysplasia ossificans progressiva. Clinical Reviews in Bone and Mineral Metabolism: 3: (3-4), 205-208.
  4. Kaplan, F.S., D. Hume, A. Westermark, and E.M. Shore (2005). The craniofacial phenotype of fibrodysplasia ossificans progressiva. Clinical Reviews in Bone and Mineral Metabolism: 3 (3-4), 209-212.
  5. Billings, P.C., Y. Wu, R. Caron, L. Serrano de la Pena, B. Young, M. Pacifici, D.L. Glaser, E.M. Shore, and F.S. Kaplan. (2005). Early fibrodysplasia ossificans progressiva-like lesion formation in nude mice following implantation of lymphoblastoid cells from FOP patients. Clinical Reviews in Bone and Mineral Metabolism: 3: (3-4), 225-228.
  6. Fiori, J.L., P.C. Billings, L. Serrano de la Pena, F.S. Kaplan, and E.M. Shore (2006). Dysregulation of the BMP-p38 MAPK signaling pathway in fibrodysplasia ossificans progressiva (FOP) patients. J. Bone Mineral Res. 21(6), 902-909. (Received 2006 Raisz-Drezner Award to Jennifer Fiori for the Best First Paper as a First Author.)
  7. Shore, E.M., M. Xu, G.J. Feldman, D.A. Fenstermacher, The FOP International Research Consortium, M.A. Brown, and F.S. Kaplan (2006). A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nature Genetics 38(5), 525-527.
  8. Jiao, X., F.S. Kaplan, P. Billings, E.M. Shore, D. Glaser (2007). Heparan sulfate proteoglycans (HSPGs) modulate BMP2 osteogenic bioactivity in C2C12 cells. J. Biol. Chem. 282 (2), 1080-1086.
  9. Kaplan, F.S. D.L. Glaser, E.M. Shore, R.J. Pignolo, M. Xu, Y. Zhang, D. Senitzer, S.J. Forman, S.G. Emerson (2007). Hematopoietic stem cell contribution to ectopic skeletogenesis. J. Bone Joint Surg (Am) 89A (2), 347-357.
  10. Yeon, H., F.S. Kaplan, E.M. Shore, A.E. Rosenberg, J. Jupiter (2007). Focal nodular heterotopic ossification: a new syndrome. J. Bone Joint Surg (Am). Am. 89(6): 1329-1336.
  11. Feldman, G.J., R.V. Patel, P.C. Billings, R.J. Caron, C. Guenther, D.M. Kingsley, F.S. Kaplan, E.M. Shore (2007). Over-expression of BMP4 and BMP5 in a child with axial skeletal malformations and heterotopic ossification: A new syndrome. Amer. J. Med. Genet. Part A. 143A, 699-706.
  12. Gelfand, I., R.S. Hub, E.M. Shore, F.S, Kaplan, L.A. DiMeglio (2007). Progressive osseous heteroplasia-like heterotopic ossification in a male infant with pseudohypoparathyroidism type Ia: A case report. Bone 40, 1425-1428.
  13. Kaplan, F.S, D.L. Glaser. R.J. Pignolo, E.M. Shore (2007). A new era in heterotopic ossification: A druggable target for the second skeleton. Expert Opin. Biol. Ther. 7 (5), 705-712.
  14. Groppe, J.C, E.M. Shore, F.S. Kaplan (2007). Functional modeling of the ACVR1 (R206H) mutation in FOP. Clin. Orthop. Rel. Res. 462, 87-92.
  15. O'Connell, M.P., P.C. Billings, J.L. Fiori, G. Deirmengian, H.I. Roach, E.M. Shore, F.S. Kaplan (2007). Heparan sulfate proteoglycan modulation of BMP signaling is altered in fibrodysplasia ossificans progressiva. J. Cell. Biochem. 102, 1493-1503.
  16. Zaghoul K.A., G.G. Heuer, M.D. Guttenberg, E.M. Shore, F.S. Kaplan, and P.B. Storm (2007). Lumbar puncture and surgical intervention in a child with undiagnosed fibrodysplasia ossificans progressiva. J. Neurosurgery: Pediatrics 1(1), 91-94.
  17. Deirmengian G.K., N.M. Hebela, M. O'Connell, E.M. Shore, D.L. Glaser, and F.S. Kaplan (2007). Proximal tibial osteochondroma in patients with fibrodysplasia ossificans progressiva. J. Bone Joint Surg. 90, 366-374.
  18. Billings P.C., J.L. Fiori, J.L. Bentwood, M.P. O'Connell, X. Jaio. B. Nussbaum, R.J. Caron, E.M. Shore, F.S. Kaplan (2008). Dysregulated BMP signaling and enhanced osteogenic differentiation of connective tissue progenitor cells from patients with fibrodysplasia ossificans progressiva (FOP). J. Bone Min. Res. 23 (3), 305-313.
  19. Kaplan, F.S., M. Xu, D.L. Glaser, F. Collins, J.M. Connor, J. Kitterman, D. Sillence, E. Zackai, V. Ravitsky, M. Zasloff, A. Ganguly, E.M. Shore (2008). Early diagnosis of fibrodysplasia ossificans progressiva (FOP). Pediatrics 121(5): e1295-1300.
  20. Adegbite, N.S, M. Xu, F.S. Kaplan, E.M. Shore*, R.J. Pignolo* (2008). Clinical features, GNAS mutational analysis, and diagnostic criteria for progressive osseous heteroplasia (POH) and POH-like syndromes. Amer. J. Med. Genetics 146A(14): 1788-1796. *Equal contributors.
  21. Moore, R.E., J.P. Dormans, D.S. Drummond, E.M. Shore, F.S. Kaplan, J.D. Auerbach (2008). Chin-on-chest deformity in patients with fibrodysplasia ossificans progressiva. J. Bone Joint Surg. In press, November 2008.
  22. Kaplan, F.S., M. Xu, P. Seemann, M. Connor, D.L. Glaser, L. Carroll, P. Delai, E. Fastnacht-Urban, S.J. Forman, G. Gillessen-Kaesbach, J. Hoover-Fong, B. Köster, R.M. Pauli, W. Reardon, S-A. Zaidi, M. Zasloff, R. Morhart, S. Mundlos, J. Groppe, E.M. Shore (2009). Classic and Atypical FOP Phenotypes are Caused by Mutations in the BMP Type I Receptor ACVR1. Human Mutation 30, 379-390.
  23. Fukuda, T, M. Kohda, K. Kanomata, J. Nojima, A. Nakamura, J. Kamizono, Y. Noguchi, K. Iwakiri, T. Kondo, J. Kurose, K. Endo, T. Awakura, J. Fukushi, Y. Nakashima, T. Chiyonobu, A. Kawara, Y. Nishida, I. Wada, M. Akita, T. Komori, K. Nakayama, A. Nanba, Y. Maruki, T. Yoda, H. Tomoda, P.B. Yu, E.M. Shore, F.S. Kaplan, K. Miyazono, M. Matsuoka, K. Ikebuchi, A. Ohtake, H. Oda, E. Jimi, I. Owan, Y. Okazaki, and T. Katagiri (2009). Constitutively activated ALK2 and increased smad1/5 cooperatively induce BMP signaling in fibrodysplasia ossificans progressiva. J. Biol. Chem. 284, 7149-7156.
  24. Huang, A.H., N.A. Motlekar, A. Stein, S.L. Diamond, E.M. Shore, R.L. Mauck (2008). High-throughput screening for modulators of mesenchymal stem cell chondrogenesis. Annals of Biomedical Engineering 36, 1909-1921.
  25. Lounev, V.Y., R. Ramachandran, M.N. Wosczyna, M. Yananoto, A.D.A. Maidment, E.M. Shore, D.L. Glaser, D.J. Goldhamer, F.S. Kaplan (2009). Identification of progenitor cells that contribute to heterotopic skeletogenesis. J. Bone Joint Surg. 91, 652-663.
  26. Suda, R.K., P.C. Billings, K.P. Egan, J.H. Kim, R. McCarrick-Walmsley, D.L. Glaser, D.L. Porter, E.M. Shore, R.J. Pignolo. (2009). Circulating osteogenic precursor cells in heterotopic bone formation. Stem Cells (ePub 6/11/09).
RECENT CONFERENCE ABSTRACTS
  1. Jiao, X., E. Shore, F. Kaplan, D. Glaser. Modulation of BMP2 bioactivity by heparan and heparin sulfate proteoglycans (HSPGs). (Presented at the Orthopaedic Research Society Annual Meeting; Washington, D.C.; February 2005.)
  2. Xu, M., F. S. Kaplan and E.M. Shore. Progressive osseous heteroplasia (POH), a human disorder of ectopic ossification, is caused by mutations in the paternally inherited allele of GNAS. (Presented at the International Meeting on Genomic Imprinting, Development and Disease; Oxford, UK; April 11-13, 2005.)
  3. O'Connell, M.P., P.C. Billings, J. Fiori, H.I. Roach, E.M.Shore and F.S. Kaplan. HSPG mediated BMP4 Signaling is Disrupted in Fibrodysplasia Ossificans Progressiva Lymphoblastiod Cells. J. Bone Min. Res. 20 (Suppl 1), S320. (Presented at the American Society for Bone and Mineral Research Annual Meeting; Nashville, TN; September 2005.)
  4. Fiori, J.L., P.C. Billings, F.S. Kaplan, and E.M. Shore. Molecular Dissection of BMP Signaling Pathways in Control and Fibrodysplasia Ossificans Progressiva Lymphoblastoid Cells. J. Bone Min. Res. 20 (Suppl 1), S107. (Presented at the American Society for Bone and Mineral Research Annual Meeting; Nashville, TN; September 2005.)
  5. Xu, M., F.S. Kaplan, and E.M. Shore. GNAS mRNAs from the Paternally-Inherited allele are Decreased in Progressive Osseous Heteroplasia (POH), a Human Disorder of Ectopic Ossification. J. Bone Min. Res. 20 (Suppl 1), S417. (Presented at the American Society for Bone and Mineral Research Annual Meeting; Nashville, TN; September 2005.)
  6. Fiori, J.L., P.C. Billings, F.S. Kaplan, and E.M. Shore. Molecular Dissection of BMP Signaling Pathways in Control and Fibrodysplasia Ossificans Progressiva Lymphoblastoid Cells. University of Pennsylvania Musculoskeletal Disorders Scientific Symposium, Philadelphia, PA; October 11, 2005. Received a First Place Poster Award in the Proteomics and Genomics category.
  7. Kanaan, R.A., F.S. Kaplan, and E.M. Shore. BMP2 signaling pathways mediate Gnas transcriptional regulation in C2C12 cells: Implications for POH disease. (Presented at University of Pennsylvania 4th Annual Postdoctoral Research Symposium. Philadelphia, PA; October 21, 2005. )
  8. O'Connell, M.P., P.C. Billings, J.L. Fiori, G. Deirmengian, H.I. Roach, E.M. Shore, and F.S. Kaplan. HSPGs Core Proteins and Glycosaminoglycan Side Chains are Elevated in the Pathological Condition Fibrodysplasia Ossificans Progressiva. (Presented at the First Joint Meeting of the Bone Research Society (BRS) and the British Orthopaedic Research Society (BORS), Southampton, UK; July 5-6, 2006.)
  9. Billings, P.C., J.L. Fiori, J.L. Bentwood, M.P. O'Connell, R.J. Caron, E.M. Shore, and F.S. Kaplan. Analysis of BMP Signal Transduction in Adherent Tooth Pulp Cells from FOP Patients. J. Bone Min. Res. 21 (Suppl 1), S209. (Presented at the American Society for Bone and Mineral Research Annual Meeting; Philadelphia, PA; September 2006.)
  10. Pignolo, R.J., N.S. Adegbite, M. Xu. F.S. Kaplan, and E.M. Shore. Clinical Features and Dignostic Criteria for Progressive Osseous Heteroplasia (POH) and POH-like Syndromes. J. Bone Min. Res. 21 (Suppl 1), S431. (Presented at the American Society for Bone and Mineral Research Annual Meeting; Philadelphia, PA; September 2006.)
  11. Kanaan, R., B. Saucy, F.S. Kaplan, and E.M. Shore. Myoblasts Are not the Likely Targets of Gs-alpha Inactivating Mutations in Progressive Osseous Heteroplasia. J. Bone Min. Res. 21 (Suppl 1), S311. (Presented at the American Society for Bone and Mineral Research Annual Meeting; Philadelphia, PA; September 2006.)
  12. Shore, E.M., M. Xu, J. Michael Connor, and F.S. Kaplan. Mutations in the BMP Receptor ACVR1 in Patients with Fibrodysplasia Ossificans Progressiva (FOP). ). J. Bone Min. Res. 21 (Suppl 1), S75. (Presented at the American Society for Bone and Mineral Research Annual Meeting; Philadelphia, PA; September 2006.) Selected as an ASBMR Newsworthy Abstract. Oral Presentation.
  13. Shore, E.M., M. Xu, and F.S. Kaplan. Allelic Variants of the Activin A Type I Receptor (ACVR1) Gene in Individuals with Atypical Features of Fibrodysplasia Ossificans Progressiva (FOP). 6th International Conference on BMPs; Dubrovnik, Croatia, October 11-15, 2006. Oral Presentation.
  14. Kaplan, F.S., M. Xu, and E.M. Shore. Why Some People Form Two Skeletons: Genetic insight into Catastrophic Heterotopic Ossification. 6th International Conference on BMPs; Dubrovnik, Croatia, October 11-15, 2006. Oral Presentation.
  15. Deirmengian, G., N. Hebela, D. Glaser, M. O'Connell, E.M. Shore, F.S. Kaplan. Proximal Tibia Osteochondromas in Patients with Fibrodysplasia Ossificans Progressiva. (Presented at the American Academy of Orthopaedic Surgery Meeting; San Diego, CA.; February 2007.) Oral Presentation.
  16. Kaplan, F. S. D. L. Glaser, R. J. Pignolo, E. M. Shore. Why Do Some People Form Two Skeletons and What Can Be Done To Stop It? (Presented at The Second Conference on Skeletal Biology and Medicine; New York Academy of Sciences and Mount Sinai School of Medicine, New York, April 25-28, 2007.) Oral Presentation.
  17. Kaplan, J.S., F.S. Kaplan, and E.M. Shore. RNAi strategies for genetic diseases of Heterotopic ossification. (Presented at the Second Annual Endocrine Fellows Research Forum; Honolulu, HI; September 2007.)
  18. Shen, Q., M. Xu, S.C. Little, F.S. Kaplan, M.C. Mullins, and E.M. Shore. Activation of BMP Signaling by the FOP ACVR1 R206H Mutation. J. Bone Min. Res. 22 (Suppl 1), S43. (Presented at the American Society for Bone and Mineral Research Annual Meeting; Honolulu, HI; September 2007.) Selected for Oral Session Presentation.
  19. Pignolo, R.J., R.K. Suda, D. Porter, E.M. Shore, and F.S. Kaplan. Circulating Osteogenic Precursor Cells of Hematopoietic Origin. J. Bone Min. Res. 22 (Suppl 1), S44-45. (Presented at the American Society for Bone and Mineral Research Annual Meeting; Honolulu, HI; September 2007.) Selected for Oral Session Presentation.
  20. Xu, M., A. Ganguly, F.S. Kaplan, and E.M. Shore. Diagnosis of Fibrodysplasia Ossificans Progressiva (FOP) Prior to the Onset of Heterotopic Ossification. J. Bone Min. Res. 22 (Suppl 1), S352. (Presented at the American Society for Bone and Mineral Research Annual Meeting; Honolulu, HI; September 2007.)
  21. Groppe, J.C., E.M. Shore, F.S. Kaplan. Homology Modeling of ACVR1 Mutations Linked to Atypical and Variant FOP Syndromes. (Presented at The Ninth International Conference on the Chemistry and Biology of Mineralized Tissues; Austin, TX. November 4-8, 2007.) Selected for Oral Session Presentation.
  22. Huang A.H., A. Stein, S.L. Diamond, E.M. Shore, R.L. Mauck. High-throughput screening of MSC chondrogenesis: Assay development and application. (Accepted; Orthopaedic Research Society Annual Meeting; San Francisco, CA; March 2008.)
  23. Bocciardi, R., D. Bordo, M. Di Duca, F.S. Kaplan, E.M. Shore, M. Di Rocco, R. Ravazzolo. Mutational analysis of the ACVR1 gene in Italian patients with fibrodysplasia ossificans progressiva (FOP). (Accepted; European Society of Human Genetics (ESHG) Annual Meeting, Barcelona, Spain; May 2008.)
  24. Lounev, V.Y., E.M. Shore, L. Kan, D.J. Goldhamer, F.S. Kaplan, and D.L. Glaser. Endothelial/hematopoietic (Tek+) cell lineages participate in heterotopic ossification. (Accepted; International Society for Stem Cell Research (ISSCR) 6th Annual Meeting, Philadelphia, PA; June 11-14, 2008.)
  25. Huang A.H., N.A. Motlekar, A. Stein, E.M. Shore, S.L. Diamond, R.L. Mauck. High-throughput screening of chemical libraries for modulators of mesenchymal stem cell chondrogenesis. (Accepted; ASME 2008 Summer Bioengineering Conference, Marco Island, FL; June 25-29, 2008.) Selected for Oral Session Presentation.
  26. Shore, E.M., Q. Shen, S.C. Little, M. Xu, J. Haupt, C. Ast, A.H. Huang, R.L. Mauck, S. Mundlos, F.S. Kaplan, P. Seemann, M.C. Mullins. The ACVR1/ALK2 R206H mutation in fibrodysplasia ossificans progressiva (FOP) stimulates ligand independent BMP signaling and chondro/osseous differentiation. (Presented at the 7th International Conference on Bone Morphogenetic Proteins; Lake Tahoe, CA; July 9-13, 2008.) Selected for Oral Presentation.
  27. Kaplan, F.S., M. Xu, J. Groppe, E.M. Shore. Ossification syndromes caused by mutations in te BMP Type I receptor ACVR1/ALK2. (Presented at the 7th International Conference on Bone Morphogenetic Proteins; Lake Tahoe, CA; July 9-13, 2008.) Selected for Oral Presentation.
  28. Wang, H., E.M. Shore, F.S. Kaplan, J. Groppe, R.J. Pignolo. Hypoxia promotes ligand-independent activation of the ACVR1 (R206H) mutant receptor in C2C12 cells. (Accepted; the American Society for Bone and Mineral Research Annual Meeting; Montreal, Canada; September 2008.)
  29. Lounev, V.Y., D.L. Glaser, E.M. Shore, and F.S. Kaplan. Connective tissue progenitor cell contribution to ectopic skeletogenesis. (Accepted; the American Society for Bone and Mineral Research Annual Meeting; Montreal, Canada; September 2008.) Selected for Plenary Poster Presentation.
  30. Chakkalakal, S., D. Zhang, T. Raabe, J. Richa, K. Hankenson, Frederick S. Kaplan, and E.M. Shore. ACVR1 knock-in mouse model for fibrodysplasia ossificans progressiva (FOP). (Accepted; the American Society for Bone and Mineral Research Annual Meeting; Montreal, Canada; September 2008.) Selected for Oral Session Presentation.
  31. Kaplan, F.S., E.M. Shore. Fibrodysplasia ossificans progressiva: When one skeleton is enough. NIH First Advances in Rare Bone Diseases Conference, Bethesda, MD. October 22-24, 2008. Selected for Oral Session Presentation.
  32. Chakkalakal, S., D. Zhang, T. Raabe, J. Richa, K. Hankenson, Frederick S. Kaplan, and E.M. Shore. ACVR1 knock-in mouse model for fibrodysplasia ossificans progressiva (FOP). 7th Annual Postdoc Research Symposium, Penn SOM; October 24, 2008. Selected for Oral Presentation.
  33. Kaplan, F.S., E.M. Shore. Cells That Build a Second Skeleton: Principles of the Metamorphosis. International Symposium on Ectopic Ossification, Royal College of Surgeons of England; London, UK. November, 2008. Invited Oral Presentation.
  34. Kaplan, F.S., E.M. Shore. FOP and its Variants. International Symposium on Ectopic Ossification, Royal College of Surgeons of England; London, UK. November, 2008. Invited Oral Presentation.
  35. Shore, E.M., F.S. Kaplan. In vivo models for fibrodysplasia ossificans progressiva. International Symposium on Ectopic Ossification, Royal College of Surgeons of England; London, UK. November, 2008. Invited Oral Presentation.
  36. Shore, E.M., F.S. Kaplan. Progressive osseous heteroplasia (POH). International Symposium on Ectopic Ossification, Royal College of Surgeons of England; London, UK. November, 2008. Invited Oral Presentation.
  37. Shore, E.M. Progressive osseous heteroplasia - a role for G-protein signaling in bone formation. 1st International Workshop on cAMP signaling and phosphodiesterases: from genetics to function and human disease. National Institutes of Health, Bethesda, MD. June, 2009. . Invited Oral Presentation.
  38. Shore, E.M. ACVR1/ALK2 mutation in fibrodysplasia ossificans progressiva (FOP). FASEB Summer Research Conference, TGF-b Superfamily: Signaling in Development and Disease, Carefree, AZ. June, 2009. . Invited Oral Presentation.
  39. Shore, E.M. "TBD." First International Workshop: Modern Trends in BMP Signaling. Berlin, Germany. September, 2009. Invited Oral Presentation.
  40. Wang, H., M. Xu, J. Groppe, T. Katagiri, E.M. Shore, F.S. Kaplan, R.J. Pignolo. BMP-independent Activation of the ACVR1 (R206H) Mutant Receptor by Hypoxia in Fibrodysplasia Ossificans Progressiva (FOP). (Accepted, the American Society for Bone and Mineral Research Annual Meeting; Denver, Colorado; September 2009.) Selected for Oral Session Presentation Selected for Oral Session Presentation
  41. Kaplan, J., F.S. Kaplan and E.M. Shore. Development of Allele-specific RNAi as a Therapeutic Strategy for Fibrodysplasia Ossificans Progressiva (FOP). (Accepted, the American Society for Bone and Mineral Research Annual Meeting; Denver, Colorado; September 2009.)
  42. Zhang, S., M. Xu, F.S. Kaplan, R.J. Pignolo, E.M. Shore. G protein-cAMP Pathway Regulates Early Stage Embryonic Stem Cell-derived Osteoblast Differentiation. (Accepted, the American Society for Bone and Mineral Research Annual Meeting; Denver, Colorado; September 2009.)

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