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Faculty Affairs: Faculty Interests Database Irving M. Shapiro, BDS, PhD

Orthopaedic Surgery
Thomas Jefferson University
Jefferson Medical College
Department of Orthopaedic Surgery
Professor of Orthopaedic Surgery, Biochemistry and Molecular Biology

Mailing Address Contact Information
1015 Walnut Street, Curtis Building, Suite 501
Philadelphia, Pennsylvania 19107
United States
Phone: (215) 955-7217
Fax: (215) 955-9159
Ph.D., University of London, Biochemistry, 1969

B.D.S., L.D.S.R.C.S. (Eng), 1964

Expertise and Research Interests
Mechanism of Bone Growth and Repair: Despite decades of study, the mechanism by which a thin layer of cartilage, the epiphyseal growth plate, regulates long bone growth remains poorly understood. Our earlier observation that the oxygen tension is a potent regulator of chondrocyte activity and mediated by the oxygen sensitive transcription factor, HIF-1, provided a new understanding of the regulatory process. The recent finding that HIF-2 is required for chondrocyte maturation and that it serves to regulate a previously unrecognized step in the maturation pathway, autophagy, holds promise of providing new insights into phase co-ordination that is especially relevant to the growth process. Our ongoing studies are directed at examining the impact of these proteins on the maturation, the extent of hypertrophy and the induction of chondrocyte mineralization and apoptosis, as well as promoting the proliferation of new cells into the maturation cascade.

Tissue Engineering of the Intervertebral Disc: Back pain, a significant source of morbidity in our society, is directly related to the pathology of the degenerate intervertebral disc. At present, the treatment of degenerative disc disease consists of therapies that are aimed at symptomatic relief. However, recent advances in the understanding of tissue repair and stem cell biology indicates that it may be possible to rebuild diseased or degenerate tissues using endogenous stem cells. The goal of our investigation is to characterize disc progenitor cells (DPC) from both normal and diseased discs. Then, to define the environmental conditions that enhance DPC differentiation into cells that exhibit the phenotypic characteristics of the inner tissue, the nucleus pulposus. Experiments are in progress to repopulate the disc in vivo by promoting the recruitment and differentiation of these endogenous stem cells.

Creating Bioactive Surfaces for Repair of Fractured and Infected Bone: The aim of this work is to develop a new generation of smart implants that promote osteogenesis and prevent bacterial infection. This study relies heavily on the development of new chemical techniques to generate linkages between metals and bioactive molecules and uses imaging techniques such as micro-tomography light, electron and X-ray imaging to evaluate efficacy of healing.

Apoptosis; autophagy; Arthritis; Biochemistry; Biomineralization; Bone; Cartilage; Growth Plate; Matrix Vesicles; Intervertebral disc, Annulus Fibrosus; HIF; Nucleus Pulposus; Orthopedics; Surgery; Tissue Engineering
  • Cheng CC, Uchiyama Y, Hiyama A, Gajghate S, Shapiro IM, Risbud MV. PI3K/AKT regulates aggrecan gene expression by modulating Sox9 expression and activity in nucleus pulposus cells of the intervertebral disc. J Cell Physiol. 2009 Dec;221(3):668-76.
  • McIlhenny SE, Hager ES, Grabo DJ, Dimatteo C, Shapiro IM, Tulenko TN, Dimuzio PJ. "Linear" Shear Conditioning Improves Vascular Graft Retention of Adipose-Derived Stem Cells by Up-regulation of the alpha5beta1 Integrin. Tissue Eng Part A. 2009 Aug 21.
  • Bohensky J, Terkhorn SP, Freeman TA, Adams CS, Garcia JA, Shapiro IM, Srinivas V. Regulation of autophagy in human and murine cartilage: hypoxia-inducible factor 2 suppresses chondrocyte autophagy. Arthritis Rheum. 2009 May;60(5):1406-15.
  • Gilbert JR, Adams CS, Shapiro IM, Hickok NJ. A novel short hairpin RNA (shRNA) expression system promotes Sox9-dependent gene silencing. Plasmid. 2009 Jul;62(1):50-5.
  • Ketonis C, Parvizi J, Adams CS, Shapiro IM, Hickok NJ. Topographic features retained after antibiotic modification of Ti alloy surfaces: retention of topography with attachment of antibiotics. Clin Orthop Relat Res. 2009 Jul;467(7):1678-87.
  • Denison TA, Koch CF, Shapiro IM, Schwartz Z, Boyan BD. Inorganic phosphate modulates responsiveness to 24,25(OH)2D3 in chondrogenic ATDC5 cells. J Cell Biochem. 2009 May 1;107(1):155-62.
  • Srinivas V, Bohensky J, Zahm AM, Shapiro IM. Autophagy in mineralizing tissues: microenvironmental perspectives. Cell Cycle. 2009 Feb 1;8(3):391-3.
  • Hiyama A, Gajghate S, Sakai D, Mochida J, Shapiro IM, Risbud MV. Activation of TonEBP by calcium controls {beta}1,3-glucuronosyl-transferase-I expression, a key regulator of glycosaminoglycan synthesis in cells of the intervertebral disc. J Biol Chem. 2009 Apr 10;284(15):9824-34.
  • Gajghate S, Hiyama A, Shah M, Sakai D, Anderson DG, Shapiro IM, Risbud MV. Osmolarity and intracellular calcium regulate aquaporin2 expression through TonEBP in nucleus pulposus cells of the intervertebral disc. J Bone Miner Res. 2009 Jun;24(6):992-1001.
  • Adams CS, Antoci V Jr, Harrison G, Patal P, Freeman TA, Shapiro IM, Parvizi J, Hickok NJ, Radin S, Ducheyne P. Controlled release of vancomycin from thin sol-gel films on implant surfaces successfully controls osteomyelitis. J Orthop Res. 2009 Jun;27(6):701-9.
  • Agrawal A, Gajghate S, Smith H, Anderson DG, Albert TJ, Shapiro IM, Risbud MV. Cited2 modulates hypoxia-inducible factor-dependent expression of vascular endothelial growth factor in nucleus pulposus cells of the rat intervertebral disc. Arthritis Rheum. 2008 Dec;58(12):3798-808.
  • Freeman TA, Patel P, Parvizi J, Antoci V Jr, Shapiro IM. Micro-CT analysis with multiple thresholds allows detection of bone formation and resorption during ultrasound-treated fracture healing. J Orthop Res. 2009 May;27 5):673-9.
  • Toworfe GK, Bhattacharyya S, Composto RJ, Adams CS, Shapiro IM, Ducheyne P. Effect of functional end groups of silane self-assembled monolayer surfaces on apatite formation, fibronectin adsorption and osteoblast cell function. J Tissue Eng Regen Med. 2009 Jan;3(1):26-36.
  • Srinivas V, Bohensky J, Shapiro IM. Autophagy: a new phase in the maturation of growth plate chondrocytes is regulated by HIF, mTOR and AMP kinase. Cells, Tissues Organs. 2009;189(1-4):88-92.
  • Zahm AM, Bucaro MA, Srinivas V, Shapiro IM, Adams CS. Oxygen tension regulates preosteocyte maturation and mineralization. Bone. 2008 Jul;43(1):25-31.Epub 2008 Mar 29.
  • Antoci V Jr, Adams CS, Parvizi J, Davidson HM, Composto RJ, Freeman TA,Wickstrom E, Ducheyne P, Jungkind D, Shapiro IM, Hickok NJ. The inhibition of Staphylococcus epidermidis biofilm formation by vancomycin-modified titanium alloy and implications for the treatment of periprosthetic infection.Biomaterials. 2008 Dec;29(35):4684-90.
  • Uchiyama Y, Guttapalli A, Gajghate S, Mochida J, Shapiro IM, Risbud MV. SMAD3 functions as a transcriptional repressor of acid-sensing ion channel 3 (ASIC3) in nucleus pulposus cells of the intervertebral disc. J Bone Miner Res. 2008 Oct;23(10):1619-28.
  • Watanabe H, Bohensky J, Freeman T, Srinivas V, Shapiro IM. Hypoxic induction of UCP3 in the growth plate: UCP3 suppresses chondrocyte autophagy. J Cell Physiol. 2008 Aug;216(2):419-25.

Last Updated by Irving Shapiro, BDS, PhD: Tuesday, October 13, 2009 7:18:04 PM

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