Wang Research

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Positions:
  • Associate Professor, Department of Medicine - Division of Endocrinology, Diabetes & Metabolic Diseases
  • Director, Animal Model Core, Center for Translational Medicine

1020 Locust Street
JAH, Room 543E
Philadelphia, PA 19107

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Highlighted Publications

Yang Y, Lei H, Wang B. Effect of the PTHrP(1-34) analog abaloparatide on inducing chondrogenesis involves inhibition of intracellular reactive oxygen species production. Biochem Biophys Res Commun. 2019 Feb 19;509(4):960-965. https://pubmed.ncbi.nlm.nih.gov › 30654932

The synthetic PTHrP(1-34) analog abaloparatide (ABL) is a newly approved drug for osteoporosis therapy. Data from this paper show that the effect of ABL on stimulation of chondrogenesis is involved in its inhibition of intracellular reactive oxygen species generation. These novel findings support the use of ABL for the damaged cartilage regeneration.  

Pera T, Deshpande DA, Ippolito M, Wang B, Gavrila A, Michael JV, Nayak AP, Tompkins E, Farrell E, Kroeze WK, Roth BL, Panettieri RA Jr., Benovic JL, An SS, Dulin NO, Penn RB. Biased signaling of the proton-sensing receptor OGR1 by benzodiazepines. FASEB journal, 2018; 32(2):862-874. https://www.ncbi.nlm.nih.gov › articles › PMC5888400

Data from this paper show that lorazepam that acts as a Gq-biased allosteric modulator of OGR1, but not sulazepam that acts as a Gs-biased allosteric modulator of OGR1, promotes calcium mobilization. Alternatively, sulazepam significantly increases CRE-Luc activity (reflective of chronic cAMP/PKA signaling) in UMR cells, whereas lorazepam is without effect. These findings suggest sulazepam biases OGR1 signaling to “tune” PTH receptor signaling toward its therapeutic pathway.

Yang Y, Lei H, Qiang YW, Wang B. Ixazomib enhances parathyroid hormone (PTH)-induced beta-catenin/T-cell factor (TCF) signaling by dissociating beta-catenin from the PTH receptor. Mol Biol Cell, 2017, 28:1792-1803. https://www.ncbi.nlm.nih.gov › articles › PMC5491187

CRISPR/Cas9 genome-editing technology was used to knock out beta-catenin expression in osteoblast-like cell line. Data from this paper show that ixazomib enhances PTH stimulation of beta-catenin/TCF signaling via cAMP-dependent activation, and this effect is due to its separating beat-catenin from the PTH receptor. These findings provide evidence that ixazomib may be used to improve the therapeutic efficacy of PTH for the treatment of osteoporosis and other resorptive bone diseases.

Yang Y, Blair HC, Shapiro IM, Wang B. The proteasome inhibitor carfilzomib suppresses parathyroid hormone-induced osteoclastogenesis through a RANKL-mediated signaling pathway. The Journal of biological chemistry. 2015; 290(27):16918-28 https://www.ncbi.nlm.nih.gov › articles › PMC4505437

Date from this paper show that carfilzomib blocks PTH-induced osteoclast formation and bone resorption by its additional effect to inhibit RANKL-mediated I kappa B degradation and NF-kappa B activation in osteoclasts. This study showed for the first time that carfilzomib targets both osteoblasts and osteoclasts to suppress PTH-induced osteoclast differentiation and bone resorption.

Yang Y, Wang B. Disruption of β-catenin binding to parathyroid hormone (PTH) receptor inhibits PTH-stimulated ERK1/2 activation. Biochemical and biophysical research communications. 2015; 464(1):27-32. https://www.ncbi.nlm.nih.gov › articles › PMC4509838

Data from this paper show that PTH-stimulated ERK1/2 activation is mostly mediated through Gq/PLC signaling pathway. Transfection of mutant PTH receptor decreased PTH-induced ERK1/2 activation by inhibiting Gq-mediated signaling. This study shows for the first time that the interference of beta-catenin binding to PTH receptor inhibits PTH-stimulated ERK1/2 phosphorylation.

Recent Publications

New role of calcium-binding fluorescent dye alizarin complexone in detecting permeability from articular cartilage to subchondral bone

PGE2 regulates expression of OATl in synoviocytes via EP4/PKA signaling pathway and effect of CP-25

Abaloparatide Maintains Normal Rat Blood Calcium Level in Part Via 1,25-Dihydroxyvitamin D/osteocalcin Signaling Pathway

Scribble scrambles parathyroid hormone receptor interactions to regulate phosphate and vitamin D homeostasis

Mutation of Methionine to Asparagine but Not Leucine in Parathyroid Hormone Mimics the Loss of Biological Function upon Oxidation

Specificity of NHERF1 regulation of GPCR signaling and function in human airway smooth muscle

Effect of the PTHrP(1-34) analog abaloparatide on inducing chondrogenesis involves inhibition of intracellular reactive oxygen species production

Biased signaling of the proton-sensing receptor OGR1 by benzodiazepines

PTH1R-CaSR Cross Talk: New Treatment Options for Breast Cancer Osteolytic Bone Metastases

Ixazomib enhances parathyroid hormone-induced ?-catenin/T-cell factor signaling by dissociating ?-catenin from the parathyroid hormone receptor

Disruption of ß-catenin binding to parathyroid hormone (PTH) receptor inhibits PTH-stimulated ERK1/2 activation

The proteasome inhibitor carfilzomib suppresses parathyroid hormone-induced osteoclastogenesis through a RANKL-mediated signaling pathway

Phosphorylation of ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) by Akt promotes stability and mitogenic function of S-phase kinase-associated protein-2 (Skp2)

Astragaloside IV possesses antiarthritic effect by preventing interleukin 1β-induced joint inflammation and cartilage damage

NHERF1 regulation of PTH-dependent bimodal Pi transport in osteoblasts

Ezrin-anchored protein kinase A coordinates phosphorylation-dependent disassembly of a NHERF1 ternary complex to regulate hormone-sensitive phosphate transport

Ubiquitination-deubiquitination balance dictates ligand-stimulated PTHR sorting

Dynamic Na +-H + exchanger regulatory factor-1 association and dissociation regulate parathyroid hormone receptor trafficking at membrane microdomains

A naturally occurring isoform inhibits parathyroid hormone receptor trafficking and signaling

Formation of a ternary complex among NHERF1, β-arrestin, and parathyroid hormone receptor

Na/H exchanger regulatory factors control parathyroid hormone receptor signaling by facilitating differential activation of Gα protein subunits

Generation of human PTH1R construct with flag epitope located internally: Comparison of two-fragment assembly by using PCR overlap extension or ligase

NHERF1 regulates parathyroid hormone receptor desensitization: Interference with β-arrestin binding

Sustained cyclic AMP production by parathyroid hormone receptor endocytosis

Na/H exchange regulatory factor 1, a novel AKT-associating protein, regulates extracellular signal-regulated kinase signaling through a B-Raf-mediated pathway