Philadelphia University + Thomas Jefferson University


Highlighted Publications

Johnson ZI, Shapiro IM, Risbud MV. (2016) 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? J Biol Chem 291(52):26686.

This study shows that TonEBP an osmoregulatory transcription factor also controls expression of several inflammatory and catabolic genes in nucleus pulposus

Choi H, Merceron C, Mangiavini L, Seifert EL, Schipani E, Shapiro IM, Risbud MV. (2016) Hypoxia promotes noncanonical autophagy in nucleus pulposus cells independent of MTOR and HIF1A signaling. Autophagy 12(9):1631.

This study, for the first time, demonstrates that NP cells do not regulate autophagy through HIF-1α under hypoxia, and that this autophagy is also uniquely MTOR-independent.

Li J, Yuan W, Jiang S, Ye W, Yang H, Shapiro IM, Risbud MV. (2015) Prolyl-4-hydroxylase domain protein 2 controls NF-κB/p65 transactivation and enhances the catabolic effects of inflammatory cytokines on cells of the nucleus pulposus. J Biol Chem 290(11):7195.

We clearly demonstrated that PHD2 forms a regulatory circuit with TNF-α via NF-κB, and therefore may play an important role in enhancing this pro-inflammatory signal during disc degeneration.

Merceron C, Mangiavini L, Robling A, Wilson TL, Giaccia AJ, Shapiro IM, Schipani E, Risbud MV. (2014) Loss of HIF-1α in the notochord results in cell death and complete disappearance of the nucleus pulposus. PLoS One 9(10):e110768.

This is the first report describing phenotype of NP-specific HIF-1α knockout mice. This study unequivocally demonstrates that HIF-1α is essential for NP cell survival and maintaining the tissue homeostasis.

Hirose Y, Johnson ZI, Schoepflin ZR, Markova DZ, Chiba K, Toyama Y, Shapiro IM, Risbud MV. (2014) FIH-1-Mint3 axis does not control HIF-1 transcriptional activity in nucleus pulposus cells. J Biol Chem 289(30):20594.

This study shows that FIH-1 activity does not regulate HIF-1-dependent transcription in NP cells, possibly as an adaptation to their unique hypoxic niche.

Recent 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

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

New horizons in spine research: Intervertebral disc repair and regeneration

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

New Horizons in Spine Research: Disc biology, spine biomechanics and pathomechanisms of back pain

Molecular mechanisms of biological aging in intervertebral discs

N-cadherin is key to expression of the nucleus pulposus cell phenotype under selective substrate culture conditions

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?

The mRNA-binding protein HuR promotes hypoxia-induced chemoresistance through posttranscriptional regulation of the proto-oncogene PIM1 in pancreatic cancer cells

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

Matrix vesicles: Are they anchored exosomes?

Understanding nucleus pulposus cell phenotype: A prerequisite for stem cell based therapies to treat intervertebral disc degeneration