Shapiro, Irving M.
Irving M. Shapiro, BDS, PhD
Curtis Building, Suite 501
Philadelphia, PA 19107
(215) 955-9159 fax
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.
Apoptosis; autophagy; Arthritis; Biochemistry; Biomineralization; Bone; Cartilage; Growth Plate; Matrix Vesicles; Intervertebral disc, Annulus Fibrosus; HIF; Nucleus Pulposus; Orthopedics; Surgery; Tissue Engineering
Most Recent Peer-Reviewed Publications
- Expression of Carbonic Anhydrase III, a Nucleus Pulposus Phenotypic Marker, is Hypoxia-responsive and Confers Protection from Oxidative Stress-induced Cell Death
- Bicarbonate Recycling by HIF-1–Dependent Carbonic Anhydrase Isoforms 9 and 12 Is Critical in Maintaining Intracellular pH and Viability of Nucleus Pulposus Cells
- The Impact of Incorporating Antimicrobials into Implant Surfaces
- Glycosaminoglycan synthesis in the nucleus pulposus: Dysregulation and the pathogenesis of disc degeneration
- A novel mouse model of intervertebral disc degeneration shows altered cell fate and matrix homeostasis
- Lack of evidence for involvement of TonEBP and hyperosmotic stimulus in induction of autophagy in the nucleus pulposus
- PHD3 is a transcriptional coactivator of HIF-1a in nucleus pulposus cells independent of the PKM2-JMJD5 axis
- TNF-α promotes nuclear enrichment of the transcription factor TonEBP/NFAT5 to selectively control inflammatory but not osmoregulatory responses in nucleus pulposus cells
- 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?
- Hypoxia promotes noncanonical autophagy in nucleus pulposus cells independent of MTOR and HIF1A signaling
- Class i and IIa HDACs Mediate HIF-1α Stability Through PHD2-Dependent Mechanism, while HDAC6, a Class IIb Member, Promotes HIF-1α Transcriptional Activity in Nucleus Pulposus Cells of the Intervertebral Disc
- Syndecan-4 in intervertebral disc and cartilage: Saint or synner?
- Circadian factors BMAL1 and RORα control HIF-1α transcriptional activity in nucleus pulposus cells: Implications in maintenance of intervertebral disc health
- TGFβ regulates Galectin-3 expression through canonical Smad3 signaling pathway in nucleus pulposus cells: Implications in intervertebral disc degeneration
- Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)
- Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356
- Matrix vesicles: Are they anchored exosomes?
- Porphyrin-adsorbed Allograft Bone: A Photoactive, Antibiofilm Surface
- The proteasome inhibitor carfilzomib suppresses parathyroid hormone-induced osteoclastogenesis through a RANKL-mediated signaling pathway
- Staphylococcal persistence due to biofilm formation in synovial fluid containing prophylactic cefazolin