Full Text Journal Articles by
Author Chih Chi Andrew Hu

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STING regulates BCR signaling in normal and malignant B cells.

Chih-Hang Anthony Tang, Avery C Lee, Shiun Chang, Qin Xu, Andong Shao, Yun Lo, Walker T Spalek, Javier A Pinilla-Ibarz, Juan R Del Valle, Chih-Chi Andrew Hu,

STING is an endoplasmic reticulum (ER)-resident protein critical for sensing cytoplasmic DNA and promoting the production of type I interferons; however, the role of STING in B cell receptor (BCR) signaling remains unclear. We generated STING V154M knock-in mice and showed that B cells carrying constitutively activated STING specifically degraded ... Read more >>

Cell Mol Immunol (Cellular & molecular immunology)
[2020, :]

Cited: 0 times

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Clarifying the translational potential of B-I09.

Juan R Del Valle, Brian C Betts, Xue-Zhong Yu, Sophie Janssens, Bart N Lambrecht, M Celeste Simon, Chih-Chi Andrew Hu,

Nat Chem Biol (Nature chemical biology)
[2020, 16(11):1152]

Cited: 0 times

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Development of tumor-targeting IRE-1 inhibitors for B cell cancer therapy.

Andong Shao, Qin Xu, Walker T Spalek, Christopher F Cain, Chang Won Kang, Chih-Hang Anthony Tang, Juan R Del Valle, Chih-Chi Andrew Hu,

The IRE-1 kinase/RNase splices the mRNA of the XBP-1 gene, resulting in the spliced XBP-1 (XBP-1s) mRNA that encodes the functional XBP-1s transcription factor that is critically important for the growth and survival of B-cell leukemia, lymphoma and multiple myeloma (MM). Several inhibitors targeting the expression of XBP-1s have been ... Read more >>

Mol Cancer Ther (Molecular cancer therapeutics)
[2020, :]

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Sel1L-Hrd1 ER-associated degradation maintains β cell identity via TGF-β signaling.

Neha Shrestha, Tongyu Liu, Yewei Ji, Rachel B Reinert, Mauricio Torres, Xin Li, Maria Zhang, Chih-Hang Anthony Tang, Chih-Chi Andrew Hu, Chengyang Liu, Ali Naji, Ming Liu, Jiandie D Lin, Sander Kersten, Peter Arvan, Ling Qi,

β Cell apoptosis and dedifferentiation are 2 hotly debated mechanisms underlying β cell loss in type 2 diabetes; however, the molecular drivers underlying such events remain largely unclear. Here, we performed a side-by-side comparison of mice carrying β cell-specific deletion of ER-associated degradation (ERAD) and autophagy. We reported that, while ... Read more >>

J Clin Invest (The Journal of clinical investigation)
[2020, 130(7):3499-3510]

Cited: 0 times

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The interdomain helix between the kinase and RNase domains of IRE1α transmits the conformational change that underlies ER stress-induced activation

Daniela Ricci, Stephen Tutton, Ilaria Marrocco, Mingjie Ying, Daniel Blumenthal, Daniela Eletto, Jade Vargas, Sarah Boyle, Hossein Fazelinia, James Paton, Adrienne Paton, Chih-Hang Anthony Tang, Chih-Chi Andrew Hu, Tali Gidalevitz, Yair Argon,

Abstract The unfolded protein response (UPR) plays an evolutionarily conserved role in homeostasis, and its dysregulation often leads to human disease, including diabetes and cancer. IRE1α is a major transducer that conveys endoplasmic reticulum (ER) stress to biochemical signals, yet major gaps persist in our understanding of how the detection ... Read more >>

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Inhibition of Human Dendritic Cell ER Stress Response Reduces T Cell Alloreactivity Yet Spares Donor Anti-tumor Immunity.

Brian C Betts, Frederick L Locke, Elizabeth M Sagatys, Joseph Pidala, Kelly Walton, Meghan Menges, Jordan Reff, Asim Saha, Julie Y Djeu, John V Kiluk, Marie C Lee, Jongphil Kim, Chang Won Kang, Chih-Hang Tang, Jeremy Frieling, Conor C Lynch, Alan List, Paulo C Rodriguez, Bruce R Blazar, Jose R Conejo-Garcia, Juan R Del Valle, Chih-Chi Hu, Claudio Anasetti,

Acute graft- vs. -host disease (GVHD) is an important cause of morbidity and death after allogeneic hematopoietic cell transplantation (HCT). We identify a new approach to prevent GVHD that impairs monocyte-derived dendritic cell (moDC) alloactivation of T cells, yet preserves graft- vs.-leukemia (GVL). Exceeding endoplasmic reticulum (ER) capacity results in ... Read more >>

Front Immunol (Frontiers in immunology)
[2018, 9:2887]

Cited: 6 times

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Phosphorylation of IRE1 at S729 regulates RIDD in B cells and antibody production after immunization.

Chih-Hang Anthony Tang, Shiun Chang, Adrienne W Paton, James C Paton, Dmitry I Gabrilovich, Hidde L Ploegh, Juan R Del Valle, Chih-Chi Andrew Hu,

To relieve endoplasmic reticulum (ER) stress, IRE1 splices XBP1 messenger RNA (mRNA) or engages regulated IRE1-dependent decay (RIDD) of other mRNAs. Upon XBP1 deficiency, IRE1 switches to perform RIDD. We examined IRE1 in XBP1-deficient B cells and discovered that IRE1 undergoes phosphorylation at S729. We generated an anti-phospho-S729 antibody to ... Read more >>

J. Cell Biol. (The Journal of cell biology)
[2018, 217(5):1739-1755]

Cited: 8 times

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Correction: Deregulation of KSHV latency conformation by ER-stress and caspase-dependent RAD21-cleavage.

Alessandra De Leo, Horng-Shen Chen, Chih-Chi Andrew Hu, Paul M Lieberman,

[This corrects the article DOI: 10.1371/journal.ppat.1006596.]. ... Read more >>

PLoS Pathog. (PLoS pathogens)
[2018, 14(4):e1007027]

Cited: 1 time

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Secretory IgM Exacerbates Tumor Progression by Inducing Accumulations of MDSCs in Mice.

Chih-Hang Tang, Shiun Chang, Ayumi Hashimoto, Yi-Ju Chen, Chang Won Kang, Anthony R Mato, Juan R Del Valle, Dmitry I Gabrilovich, Chih-Chi Hu,

Chronic lymphocytic leukemia (CLL) cells can secrete immunoglobulin M. However, it is not clear whether secretory IgM (sIgM) plays a role in disease progression. We crossed the Eμ-TCL1 mouse model of CLL, in which the expression of human TCL1 oncogene was driven by the V(H) promoter-Ig(H)-Eμ enhancer, with MD4 mice ... Read more >>

Cancer Immunol Res (Cancer immunology research)
[2018, 6(6):696-710]

Cited: 4 times

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IRE1α RNase-dependent lipid homeostasis promotes survival in Myc-transformed cancers.

Hong Xie, Chih-Hang Anthony Tang, Jun H Song, Anthony Mancuso, Juan R Del Valle, Jin Cao, Yan Xiang, Chi V Dang, Roy Lan, Danielle J Sanchez, Brian Keith, Chih-Chi Andrew Hu, M Celeste Simon,

Myc activation is a primary oncogenic event in many human cancers; however, these transcription factors are difficult to inhibit pharmacologically, suggesting that Myc-dependent downstream effectors may be more tractable therapeutic targets. Here, we show that Myc overexpression induces endoplasmic reticulum (ER) stress and engages the inositol-requiring enzyme 1α (IRE1α)/X-box binding ... Read more >>

J Clin Invest (The Journal of clinical investigation)
[2018, 128(4):1300-1316]

Cited: 7 times

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Inhibition of the IRE-1α/XBP-1 pathway prevents chronic GVHD and preserves the GVL effect in mice.

Steven D Schutt, Yongxia Wu, Chih-Hang Anthony Tang, David Bastian, Hung Nguyen, M Hanief Sofi, MengMeng Zhang, Chen Liu, Kris Helke, Carole Wilson, Lynn M Schnapp, Juan R Del Valle, Chih-Chi Andrew Hu, Xue-Zhong Yu,

Hematopoietic stem cell transplantation (HCT) is a curative procedure for hematological malignancies, but chronic graft-versus-host disease (cGVHD) remains a major complication after allogeneic HCT. Because donor B cells are essential for cGVHD development and B cells are sensitive to endoplasmic reticulum (ER) stress, we hypothesized that the IRE-1α/XBP-1 pathway is ... Read more >>

Blood Adv (Blood advances)
[2018, 2(4):414-427]

Cited: 8 times

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Regulated IRE1-dependent mRNA decay sets the threshold for dendritic cell survival.

Simon J Tavernier, Fabiola Osorio, Lana Vandersarren, Jessica Vetters, Nele Vanlangenakker, Gert Van Isterdael, Karl Vergote, Riet De Rycke, Eef Parthoens, Lianne van de Laar, Takao Iwawaki, Juan R Del Valle, Chih-Chi Andrew Hu, Bart N Lambrecht, Sophie Janssens,

The IRE1-XBP1 signalling pathway is part of a cellular programme that protects against endoplasmic reticulum (ER) stress, but also controls development and survival of immune cells. Loss of XBP1 in splenic type 1 conventional dendritic cells (cDC1s) results in functional alterations without affecting cell survival. However, in mucosal cDC1s, loss ... Read more >>

Nat Cell Biol (Nature cell biology)
[2017, 19(6):698-710]

Cited: 26 times

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Site-specific Proteolysis Mobilizes TorsinA from the Membrane of the Endoplasmic Reticulum (ER) in Response to ER Stress and B Cell Stimulation.

Chenguang Zhao, Rebecca S H Brown, Chih-Hang Anthony Tang, Chih-Chi Andrew Hu, Christian Schlieker,

Torsin ATPases are the only representatives of the AAA+ ATPase family that reside in the lumen of the endoplasmic reticulum (ER) and nuclear envelope. Two of these, TorsinA and TorsinB, are anchored to the ER membrane by virtue of an N-terminal hydrophobic domain. Here we demonstrate that the imposition of ... Read more >>

J Biol Chem (The Journal of biological chemistry)
[2016, 291(18):9469-9481]

Cited: 12 times

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Agonist-Mediated Activation of STING Induces Apoptosis in Malignant B Cells.

Chih-Hang Anthony Tang, Joseph A Zundell, Sujeewa Ranatunga, Cindy Lin, Yulia Nefedova, Juan R Del Valle, Chih-Chi Andrew Hu,

Endoplasmic reticulum (ER) stress responses through the IRE-1/XBP-1 pathway are required for the function of STING (TMEM173), an ER-resident transmembrane protein critical for cytoplasmic DNA sensing, IFN production, and cancer control. Here we show that the IRE-1/XBP-1 pathway functions downstream of STING and that STING agonists selectively trigger mitochondria-mediated apoptosis ... Read more >>

Cancer Res (Cancer research)
[2016, 76(8):2137-2152]

Cited: 53 times

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Aging: mitigation and intervention strategies.

Chi-Feng Hung, Jorge Azofeifa-Navas, Huanran Tan, Chih-Chi Andrew Hu, Nicole Clarke,

Biomed Res Int (BioMed research international)
[2015, 2015:276539]

Cited: 0 times

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Inhibition of ER stress-associated IRE-1/XBP-1 pathway reduces leukemic cell survival.

Chih-Hang Anthony Tang, Sujeewa Ranatunga, Crystina L Kriss, Christopher L Cubitt, Jianguo Tao, Javier A Pinilla-Ibarz, Juan R Del Valle, Chih-Chi Andrew Hu,

Activation of the ER stress response is associated with malignant progression of B cell chronic lymphocytic leukemia (CLL). We developed a murine CLL model that lacks the ER stress-associated transcription factor XBP-1 in B cells and found that XBP-1 deficiency decelerates malignant progression of CLL-associated disease. XBP-1 deficiency resulted in ... Read more >>

J. Clin. Invest. (The Journal of clinical investigation)
[2014, 124(6):2585-2598]

Cited: 75 times

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IgG1+ ovalbumin-specific B-cell transnuclear mice show class switch recombination in rare allelically included B cells.

Stephanie K Dougan, Souichi Ogata, Chih-Chi Andrew Hu, Gijsbert M Grotenbreg, Eduardo Guillen, Rudolf Jaenisch, Hidde L Ploegh,

We used somatic cell nuclear transfer (SCNT) to generate a mouse from the nucleus of an IgG1(+) ovalbumin-specific B cell. The resulting OBI mice show generally normal B-cell development, with elevated percentages of marginal zone B cells and a reduction in B-1 B cells. Whereas OBI RAG1(-/-) mice have exclusively ... Read more >>

Proc. Natl. Acad. Sci. U.S.A. (Proceedings of the National Academy of Sciences of the United States of America)
[2012, 109(34):13739-13744]

Cited: 22 times

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Synthesis and evaluation of substituted hexahydronaphthalenes as novel inhibitors of the Mcl-1/BimBH3 interaction.

Young B Kim, Maria E Balasis, Kenichiro Doi, Norbert Berndt, Courtney DuBoulay, Chih-Chi Andrew Hu, Wayne Guida, Hong-Gang Wang, Saïd M Sebti, Juan R Del Valle,

Mcl-1, an anti-apoptotic member of the Bcl-2 protein family, is overexpressed in a broad range of human cancers and plays a critical role in conferring resistance to chemotherapy. In the course of screening a natural product-like library of sesquiterpenoid analogs, we identified substituted hexahydronaphthalenes that showed activity against the Mcl-1/BimBH3 ... Read more >>

Bioorg Med Chem Lett (Bioorganic & medicinal chemistry letters)
[2012, 22(18):5961-5965]

Cited: 3 times

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Overexpression of TCL1 activates the endoplasmic reticulum stress response: a novel mechanism of leukemic progression in mice.

Crystina L Kriss, Javier A Pinilla-Ibarz, Adam W Mailloux, John J Powers, Chih-Hang Anthony Tang, Chang Won Kang, Nicola Zanesi, Pearlie K Epling-Burnette, Eduardo M Sotomayor, Carlo M Croce, Juan R Del Valle, Chih-Chi Andrew Hu,

Chronic lymphocytic leukemia (CLL) represents 30% of adult leukemia. TCL1 is expressed in ~ 90% of human CLL. Transgenic expression of TCL1 in murine B cells (Eμ-TCL1) results in mouse CLL. Here we show for the first time that the previously unexplored endoplasmic reticulum (ER) stress response is aberrantly activated ... Read more >>

Blood (Blood)
[2012, 120(5):1027-1038]

Cited: 32 times

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XBP-1-deficient plasmablasts show normal protein folding but altered glycosylation and lipid synthesis.

Annette M McGehee, Stephanie K Dougan, Elizabeth J Klemm, Guanghou Shui, Boyoun Park, You-Me Kim, Nicki Watson, Markus R Wenk, Hidde L Ploegh, Chih-Chi Andrew Hu,

The accumulation of misfolded secreted IgM in the endoplasmic reticulum (ER) of X-box binding protein 1 (XBP-1)-deficient B cells has been held responsible for the inability of such cells to yield plasma cells, through the failure to mount a proper unfolded protein response. LPS-stimulated B cells incapable of secreting IgM ... Read more >>

J Immunol (Journal of immunology (Baltimore, Md. : 1950))
[2009, 183(6):3690-3699]

Cited: 27 times

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XBP-1 regulates signal transduction, transcription factors and bone marrow colonization in B cells.

Chih-Chi Andrew Hu, Stephanie K Dougan, Annette M McGehee, J Christopher Love, Hidde L Ploegh,

XBP-1, a transcription factor that drives the unfolded protein response (UPR), is activated in B cells when they differentiate to plasma cells. Here, we show that in the B cells, whose capacity to secrete IgM has been eliminated, XBP-1 is induced normally on induction of differentiation, suggesting that activation of ... Read more >>

EMBO J. (The EMBO journal)
[2009, 28(11):1624-1636]

Cited: 99 times

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Profiling antibody responses by multiparametric analysis of primary B cells.

Craig M Story, Eliseo Papa, Chih-Chi Andrew Hu, Jehnna L Ronan, Kara Herlihy, Hidde L Ploegh, J Christopher Love,

Determining the efficacy of a vaccine generally relies on measuring neutralizing antibodies in sera. This measure cannot elucidate the mechanisms responsible for the development of immunological memory at the cellular level, however. Quantitative profiles that detail the cellular origin, extent, and diversity of the humoral (antibody-based) immune response would improve ... Read more >>

Proc Natl Acad Sci U S A (Proceedings of the National Academy of Sciences of the United States of America)
[2008, 105(46):17902-17907]

Cited: 33 times

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Synergism of Rana catesbeiana ribonuclease and IFN-gamma triggers distinct death machineries in different human cancer cells.

Chih-Hang Anthony Tang, Chih-Chi Andrew Hu, Chyou-Wei Wei, Jaang-Jiun Wang,

Rana catesbeiana ribonuclease (RC-RNase) possesses tumor-specific cytotoxicity, which can be synergized by IFN-gamma. However, it is unclear how RC-RNase and RC-RNase/IFN-gamma induce cell death. In this study, we use substrate cleavage assays to systematically investigate RC-RNase- and RC-RNase/IFN-gamma-induced caspase activation in HL-60, MCF-7, and SK-Hep-1 cells. We find that RC-RNase ... Read more >>

FEBS Lett. (FEBS letters)
[2005, 579(1):265-270]

Cited: 15 times

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Overexpression of tumor susceptibility gene TSG101 in human papillary thyroid carcinomas.

Rue-Tsuan Liu, Chao-Cheng Huang, Huey-Ling You, Fong-Fu Chou, Chih-Chi Andrew Hu, Fang-Ping Chao, Ching-Mei Chen, Jiin-Tsuey Cheng,

Functional inactivation of tumor susceptibility gene tsg101 leads to cellular transformation and tumorigenesis in mice. While human TSG101 is located in a region where frequent loss of heterozygosity can be detected in a variety of cancers, no genomic deletion in TSG101 gene has been reported, casting a doubt on the ... Read more >>

Oncogene (Oncogene)
[2002, 21(31):4830-4837]

Cited: 42 times

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Induction of differentiation rescues HL-60 cells from Rana catesbeiana ribonuclease-induced cell death.

Chyou Wei Wei, Chih Chi Andrew Hu, Chih Hang Anthony Tang, Ming Chieh Lee, Jaang Jiun Wang,

Rana catesbeiana ribonuclease (RC-RNase) exerted strong anti-tumor activity and its cytotoxicity was shown to correlate with differentiation stages of three different hepatoma cell lines. In this study, we demonstrate different RC-RNase cytotoxicity in undifferentiated HL-60 cells and in those that had been induced to differentiate by retinoic acid or dimethylsulfoxide. ... Read more >>

FEBS Lett. (FEBS letters)
[2002, 531(3):421-426]

Cited: 15 times

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