Biao Wang

All Publications

• Optogenetic Regulation of Aqueous Outflow in Mouse Trabecular Meshwork Alvarado, J. A., Prosseda, P. P., Luo, N., Wang, B., Ning, K., He, W., Kowal, T., Sun, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018

  View details for Web of Science ID 000442932804178

• The role of inositol phosphatase OCRL in microtubule nucleation: Implications for Oculocerebrorenal Syndrome of Lowe Wang, B., Prosseda, P. P., He, W., Kowal, T., Alvarado, J. A., Ning, K., Sun, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018

  View details for Web of Science ID 000442912509107

• Loss of OCRL increases ciliary PI(4,5)P2 in Lowe oculocerebrorenal syndrome. Journal of cell science Prosseda, P. P., Luo, N., Wang, B., Alvarado, J. A., Hu, Y., Sun, Y. 2017; 130 (20): 3447?54

  Abstract

  Lowe syndrome is a rare X-linked disorder characterized by bilateral congenital cataracts and glaucoma, mental retardation, and proximal renal tubular dysfunction. Mutations in OCRL, an inositol polyphosphate 5-phosphatase that dephosphorylates PI(4,5)P2, cause Lowe syndrome. Previously we showed that OCRL localizes to the primary cilium, which has a distinct membrane phospholipid composition, but disruption of phosphoinositides in the ciliary membrane is poorly understood. Here, we demonstrate that cilia from Lowe syndrome patient fibroblasts exhibit increased levels of PI(4,5)P2 and decreased levels of PI4P. In particular, subcellular distribution of PI(4,5)P2 build-up was observed at the transition zone. Accumulation of ciliary PI(4,5)P2 was pronounced in mouse embryonic fibroblasts (MEFs) derived from Lowe syndrome mouse model as well as in Ocrl-null MEFs, which was reversed by reintroduction of OCRL. Similarly, expression of wild-type OCRL reversed the elevated PI(4,5)P2 in Lowe patient cells. Accumulation of sonic hedgehog protein in response to hedgehog agonist was decreased in MEFs derived from a Lowe syndrome mouse model. Together, our findings show for the first time an abnormality in ciliary phosphoinositides of both human and mouse cell models of Lowe syndrome.

  View details for PubMedID 28871046

• EGFR regulates iron homeostasis to promote cancer growth through redistribution of transferrin receptor 1 CANCER LETTERS Wang, B., Zhang, J., Song, F., Tian, M., Shi, B., Jiang, H., Xu, W., Wang, H., Zhou, M., Pan, X., Gu, J., Yang, S., Jiang, L., Li, Z. 2016; 381 (2): 331-340

  Abstract

  Dysregulation in iron metabolism can lead to a wide range of diseases including cancer. Iron-regulatory proteins (IRPs) and iron responsive elements (IREs) have been established as post-transcriptional regulators of intracellular iron homeostasis. The roles of other pathways involved in this process, however, remain largely unknown. Here we report that epidermal growth factor receptor (EGFR), an oncogenic driver, binds to and regulates the subcellular distribution of transferrin receptor 1(TfR1) through its tyrosine kinase activity and thus is required for cellular iron import. Inactivation of EGFR reduces the cell surface TfR1 expression, which leads to decreased iron import due to impaired TfR1-mediated iron uptake. This damaged iron assimilation results in cell cycle arrest and growth inhibition, which can be partially rescued by non-Tf-bound iron supplements. Evaluation of non-small cell lung cancer samples reveals a positive correlation between EGFR activation and membrane TfR1 expression. Our findings uncover a new role of EGFR in modulating cellular iron homeostasis through redistribution of TfR1, which is essential for cancer development and progression.

  View details for DOI 10.1016/j.canlet.2016.08.006

  View details for Web of Science ID 000385332400007

  View details for PubMedID 27523281

• Weak binding to E3 ubiquitin ligase c-Cbl increases EGFRvA protein stability FEBS LETTERS Song, F., Zhou, M., Wang, B., Shi, B., Jiang, H., Zhang, J., Li, Z. 2016; 590 (9): 1345-1353

  Abstract

  Recently, we have identified a novel epidermal growth factor receptor isoform (EGFRvA), which has higher tumor-promoting capacity than EGFR. However, the underlying mechanism is not well understood. Here, we demonstrate that EGFRvA is more stable than EGFR. Interestingly, we observe that EGFRvA binds less to E3 ubiquitin ligase c-Cbl than EGFR does, although Y1045, a direct binding site of c-Cbl, is well phosphorylated in both of them. Further study reveals that EGFRvA cannot bind to Grb2, an important binding mediator between EGFR and c-Cbl. Thus, our study finds that EGFRvA is more stable than EGFR because of its decreased binding to c-Cbl.

  View details for DOI 10.1002/1873-3468.12166

  View details for Web of Science ID 000375528800006

  View details for PubMedID 27059931

• Combination of an anti-EGFRvIII antibody CH12 with Rapamycin synergistically inhibits the growth of EGFRvIII(+)PTEN(-) glioblastoma in vivo ONCOTARGET Xu, W., Bi, Y., Kong, J., Zhang, J., Wang, B., Li, K., Tian, M., Pan, X., Shi, B., Gu, J., Jiang, H., Kong, X., Li, Z. 2016; 7 (17): 24752-24765

  Abstract

  There are still unmet medical needs for the treatment of glioblastoma (GBM), the most frequent and aggressive brain tumor worldwide. EGFRvIII, overexpressed in approximately 30% of GBM, has been regarded as a potential therapeutic target. In this study, we demonstrated that CH12, an anti-EGFRvIII monoclonal antibody, could significantly suppress the growth of EGFRvIII+ GBM in vivo; however, PTEN deficiency in GBM reduced the efficacy of CH12 by attenuating its effect on PI3K/AKT/mTOR pathway. To overcome this problem, CH12 was combined with the mTOR inhibitor rapamycin, leading to a synergistic inhibitory effect on EGFRvIII+PTEN- GBM in vivo. Mechanistically, the synergistic antitumor effect was achieved via attenuating EGFR and PI3K/AKT/mTOR pathway more effectively and reversing the STAT5 activation caused by rapamycin treatment. Moreover, the combination therapy suppressed angiogenesis and induced cancer cell apoptosis more efficiently. Together, these results indicated that CH12 and rapamycin could synergistically suppress the growth of EGFRvIII+PTEN- GBM, which might have a potential clinical application in the future.

  View details for DOI 10.18632/oncotarget.8407

  View details for Web of Science ID 000377706200137

  View details for PubMedID 27029073

  View details for PubMedCentralID PMC5029739

• Synergistic antitumor efficacy against the EGFRvIII(+)HER2(+) breast cancers by combining trastuzumab with anti-EGFRvIII antibody CH12 ONCOTARGET Xu, W., Bi, Y., Zhang, J., Kong, J., Jiang, H., Tian, M., Li, K., Wang, B., Chen, C., Song, F., Pan, X., Shi, B., Kong, X., Gu, J., Cai, X., Li, Z. 2015; 6 (36): 38840-38853

  Abstract

  Although Trastuzumab, an anti-HER2 antibody, benefits certain patients with HER2-overexpressing breast cancer, de novo or acquired trastuzumab resistance remains a haunting issue. EGFRvIII, co-expressing with HER2 in some breast tumors, indicates a poor clinical prognosis. However, the role of EGFRvIII in the function of trastuzumab is not clear. Here, we demonstrated that EGFRvIII overexpression contributed to de novo trastuzumab resistance and the feedback activation of STAT3 caused by trastuzumab also resulted in acquired resistance in EGFRvIII(+)HER2(+) breast cancers. CH12, a highly effective anti-EGFRvIII monoclonal antibody that preferentially binds to EGFRvIII, significantly suppressed the growth of EGFRvIII+HER2(+) breast cancer cells in vitro and in vivo. Importantly, CH12 in combination with trastuzumab had a synergistic inhibitory effect on EGFRvIII(+)HER2(+) breast cancers in vitro and in vivo via attenuating the phosphorylation of EGFR and HER2 and their downstream signal pathways more effectively and reversing STAT3 feedback activation. Moreover, the combination therapy suppressed angiogenesis and induced cell apoptosis significantly. Together, these results suggested a synergistic efficacy of the combination of trastuzumab with CH12 against EGFRvIII(+)HER2(+) breast cancers, which might be a potential clinical application in the future.

  View details for Web of Science ID 000366114000032

  View details for PubMedID 26474285

  View details for PubMedCentralID PMC4770741

• Disturbance of Copper Homeostasis Is a Mechanism for Homocysteine-Induced Vascular Endothelial Cell Injury PLOS ONE Dong, D., Wang, B., Yin, W., Ding, X., Yu, J., Kang, Y. J. 2013; 8 (10)

  Abstract

  Elevation of serum homocysteine (Hcy) levels is a risk factor for cardiovascular diseases. Previous studies suggested that Hcy interferes with copper (Cu) metabolism in vascular endothelial cells. The present study was undertaken to test the hypothesis that Hcy-induced disturbance of Cu homeostasis leads to endothelial cell injury. Exposure of human umbilical vein endothelial cells (HUVECs) to concentrations of Hcy at 0.01, 0.1 or 1 mM resulted in a concentration-dependent decrease in cell viability and an increase in necrotic cell death. Pretreatment of the cells with a final concentration of 5 µM Cu in cultures prevented the effects of Hcy. Hcy decreased intracellular Cu concentrations. HPLC-ICP-MS analysis revealed that Hcy caused alterations in the distribution of intracellular Cu; more Cu was redistributed to low molecular weight fractions. ESI-Q-TOF detected the formation of Cu-Hcy complexes. Hcy also decreased the protein levels of Cu chaperone COX17, which was accompanied by a decrease in the activity of cytochrome c oxidase (CCO) and a collapse of mitochondrial membrane potential. These effects of Hcy were all preventable by Cu pretreatment. The study thus demonstrated that Hcy disturbs Cu homeostasis and limits the availability of Cu to critical molecules such as COX17 and CCO, leading to mitochondrial dysfunction and endothelial cell injury.

  View details for DOI 10.1371/journal.pone.0076209

  View details for Web of Science ID 000326029300014

  View details for PubMedID 24204604

  View details for PubMedCentralID PMC3799909

• Copper chaperone for superoxide dismutase-1 transfers copper to mitochondria but does not affect cytochrome c oxidase activity EXPERIMENTAL BIOLOGY AND MEDICINE Wang, B., Dong, D., Kang, Y. J. 2013; 238 (9): 1017-1023

  Abstract

  Copper chaperone for superoxide dismutase-1 (CCS-1) is present in the cytosol and in the intermembrane space of mitochondria. It transfers copper ions to superoxide dismutase 1 in the cytosol, but its function in the mitochondria is not clear. The present study was undertaken to test the hypothesis that CCS-1 functions in mitochondrial copper homeostasis. Mitochondria were isolated from human umbilical vein endothelial cells and copper concentrations in the mitochondria were measured in the CCS-1 deficient cells made by siRNA targeting the protein. Copper concentrations in the mitochondria were about 10 fold higher than its total concentrations in the cell and the CCS-1 deficiency significantly reduced the copper level in the mitochondria. However, this decrease in the mitochondrial copper concentration did not affect cytochrome c oxidase (CCO) activity. On the other hand, siRNA targeting COX17, a copper chaperone for the CCO, significantly increased the mitochondrial copper concentration, but suppressed the CCO activity. This study thus demonstrates that CCS-1 facilitates copper trafficking to the mitochondria, but does not affect the transfer of copper to the CCO. In addition, the COX17 not only functions in the copper shuttling to the CCO, but also may participate in the copper efflux from the mitochondria.

  View details for DOI 10.1177/1535370213497327

  View details for Web of Science ID 000324584000005

  View details for PubMedID 23900152