Philadelphia University + Thomas Jefferson University

Shapiro, Irving M.

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Irving M. Shapiro, BDS, PhD

Contact Dr. Shapiro

1015 Walnut Street
Curtis Building, Suite 501
Philadelphia, PA 19107

(215) 955-7217
(215) 955-9159 fax

Medical School

PhD, University of London, Biochemistry - 1969
BDS, LDSRCS (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.

Keywords

Apoptosis; autophagy; Arthritis; Biochemistry; Biomineralization; Bone; Cartilage; Growth Plate; Matrix Vesicles; Intervertebral disc, Annulus Fibrosus; HIF; Nucleus Pulposus; Orthopedics; Surgery; Tissue Engineering

Publications

Most Recent Peer-Reviewed Publications

  1. RNA sequencing reveals a role of TonEBP transcription factor in regulation of pro-inflammatory genes in response to hyperosmolarity in healthy nucleus pulposus cells a homeostatic response?
  2. Hypoxia promotes noncanonical autophagy in nucleus pulposus cells independent of MTOR and HIF1A signaling
  3. Syndecan-4 in intervertebral disc and cartilage: Saint or synner?
  4. Matrix vesicles: Are they anchored exosomes?
  5. Porphyrin-adsorbed Allograft Bone: A Photoactive, Antibiofilm Surface
  6. eNOS transfection of adipose-derived stem cells yields bioactive nitric oxide production and improved results in vascular tissue engineering
  7. Loss of HIF-1α in the notochord results in cell death and complete disappearance of the nucleus pulposus
  8. FIH-1-Mint3 axis does not control HIF-1α transcriptional activity in nucleus pulposus cells
  9. CCN2 suppresses catabolic effects of interleukin-1β through α5β1 and αVβ3 Integrins in nucleus pulposus cells: Implications in intervertebral disc degeneration
  10. Prosthesis Selection
  11. Introduction to the structure, function, and comparative anatomy of the vertebrae and the intervertebral disc
  12. Microenvironmental control of disc cell function: Influence of hypoxia and osmotic pressure
  13. The intervertebral disc: Molecular and structural studies of the disc in health and disease
  14. Role of cytokines in intervertebral disc degeneration: Pain and disc content
  15. Extracellular osmolarity regulates matrix homeostasis in the intervertebral disc and articular cartilage: Evolving role of TonEBP
  16. Boning up on autophagy :The role of autophagy in skeletal biology
  17. Tumor necrosis factor-α- and interleukin-1β-dependent matrix metalloproteinase-3 expression in nucleus pulposus cells requires cooperative signaling via syndecan 4 and mitogen-activated protein kinase-NF-κB axis: Implications in inflammatory disc disease
  18. Xylosyltransferase-1 expression is refractory to inhibition by the inflammatory cytokines tumor necrosis factor α and IL-1β in nucleus pulposus cells: Novel regulation by AP-1, Sp1, and Sp3
  19. HIF-1-PHD2 axis controls expression of syndecan 4 in nucleus pulposus cells
  20. Prosthesis selection