Xiaonan Dong
University of Texas Southwestern Medical Center
Network
Latest external collaboration on country level. Dive into details by clicking on the dots.
Publication
Featured researches published by Xiaonan Dong.
Journal of Innate Immunity | 2013
Xiaonan Dong; Beth Levine
The autophagy pathway is an essential component of host defense against viral infection, orchestrating pathogen degradation (xenophagy), innate immune signaling, and certain aspects of adaptive immunity. Single autophagy proteins or cassettes of the core autophagy machinery can also function as antiviral factors independently of the canonical autophagy pathway. Moreover, to survive and propagate within the host, viruses have evolved a variety of strategies to evade autophagic attack and manipulate the autophagy machinery for their own benefit. This review summarizes recent advances in understanding the antiviral and proviral roles of autophagy and previously unappreciated autophagy-independent functions of autophagy-related genes.
Trends in Cell Biology | 2015
Beth Levine; Rong Liu; Xiaonan Dong; Qing Zhong
The Beclin family, including yeast Atg6 (autophagy related gene 6), its orthologs in higher eukaryotic species, and the more recently characterized mammalian-specific Beclin 2, are essential molecules in autophagy and other membrane-trafficking events. Extensive studies of Beclin orthologs have provided considerable insights into the regulation of autophagy, the diverse roles of autophagy in physiology and disease, and potential new strategies to modulate autophagy in a variety of clinical diseases. In this review we discuss the functions of Beclin orthologs, the regulation of such functions by diverse cellular signaling pathways, and the effects of such regulation on downstream cellular processes including tumor suppression and metabolism. These findings suggest that Beclin orthologs serve as crucial molecules that integrate diverse environmental signals with membrane trafficking events to ensure optimal responses of the cell to stressful stimuli.
Oncogene | 2015
Haiyan Dong; Linlu Tian; Rui Li; Chunying Pei; Y Fu; Xiaonan Dong; Fucan Xia; Chaodong Wang; Wei Li; Xize Guo; Changcong Gu; Bin Li; A Liu; Huan Ren; Hongwei Xu
Interferon gamma (IFNg) has been known as the regulator for both tumor immune surveillance and tumorgenesis. However, mechanisms underlying the resistance of tumor cell to IFNg have yet been fully understood. In the current study, we showed that immunity-related GTPase family member 1 (mouse: Irgm1; human: IRGM) is essential for IFNg-mediated regulation of tumor cell growth in melanoma. IRGM/Irgm1 was highly expressed in human and mouse melanoma. IFNg and starvation synergistically induced Irgm1 expression in melanoma B16 cells. In vivo, injection of Irgm1-siRNA-treated cells significantly reduced the number of tumor nodules and prolonged the mice survival. In vitro, knockdown endogenous or IFNg-induced Irgm1 significantly decreases the proliferation and increases apoptosis of B16 cells. In addition, suppressing Irgm1 decreased the IFNg/starvation-induced autophagy, while overexpressing Irgm1 significantly increased autophagy and rescued starvation-challenged cells. Moreover, IFNg and starvation-induced the co-localization of Irgm1 with Bax-interacting factor 1 (Bif-1). Knockdown of Bif-1 decreased Irgm1-mediated tumor cell autophagy. Taken together, these data reveal an Irgm1-dependent mechanism that promotes the tumorigenesis of melanoma via dual regulation of apoptosis and Bif-1-dependent autophagy.
Proceedings of the National Academy of Sciences of the United States of America | 2016
Xiaonan Dong; Adam Cheng; Zhongju Zou; Yih Sheng Yang; Rhea Sumpter; Chou Long Huang; Govind Bhagat; Herbert W. Virgin; Sergio A. Lira; Beth Levine
Significance We show that the autophagy-related protein Beclin 2 functions as a newly described cellular regulator of viral G protein-coupled receptors (GPCRs) and as a suppressor of viral GPCR-driven tumorigenesis. Beclin 2 functions in regulating Kaposi’s sarcoma-associated herpesvirus-encoded GPCR levels, proinflammatory signaling, and oncogenic activity in mice by facilitating viral GPCR endolysosomal trafficking. This Beclin 2-dependent endolysosomal trafficking and degradation of an oncogenic viral protein may represent a broader and heretofore unappreciated role of the endolysosomal trafficking machinery in innate immunity (by defending against microbial virulence factors) and in tumor suppression (by degrading oncogenic cell surface receptors). The ubiquitin-proteasome system degrades viral oncoproteins and other microbial virulence factors; however, the role of endolysosomal degradation pathways in these processes is unclear. Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi’s sarcoma, and a constitutively active viral G protein-coupled receptor (vGPCR) contributes to the pathogenesis of KSHV-induced tumors. We report that a recently discovered autophagy-related protein, Beclin 2, interacts with KSHV GPCR, facilitates its endolysosomal degradation, and inhibits vGPCR-driven oncogenic signaling. Furthermore, monoallelic loss of Becn2 in mice accelerates the progression of vGPCR-induced lesions that resemble human Kaposi’s sarcoma. Taken together, these findings indicate that Beclin 2 is a host antiviral molecule that protects against the pathogenic effects of KSHV GPCR by facilitating its endolysosomal degradation. More broadly, our data suggest a role for host endolysosomal trafficking pathways in regulating viral pathogenesis and oncogenic signaling.
Journal of Biomolecular Screening | 2015
Rui Zhong; Xiaonan Dong; Beth Levine; Yang Xie; Guanghua Xiao
High-throughput RNA interference (RNAi) screening has opened up a path to investigating functional genomics in a genome-wide pattern. However, such studies are often restricted to assays that have a single readout format. Recently, advanced image technologies have been coupled with high-throughput RNAi screening to develop high-content screening, in which one or more cell image(s), instead of a single readout, were generated from each well. This image-based high-content screening technology has led to genome-wide functional annotation in a wider spectrum of biological research studies, as well as in drug and target discovery, so that complex cellular phenotypes can be measured in a multiparametric format. Despite these advances, data analysis and visualization tools are still largely lacking for these types of experiments. Therefore, we developed iScreen (image-Based High-content RNAi Screening Analysis Tool), an R package for the statistical modeling and visualization of image-based high-content RNAi screening. Two case studies were used to demonstrate the capability and efficiency of the iScreen package. iScreen is available for download on CRAN (http://cran.cnr.berkeley.edu/web/packages/iScreen/index.html). The user manual is also available as a supplementary document.
Cell | 2013
Congcong He; Yongjie Wei; Kai Sun; Binghua Li; Xiaonan Dong; Zhongju Zou; Yang Liu; Lisa N. Kinch; Shaheen Khan; Sangita C. Sinha; Ramnik J. Xavier; Nick V. Grishin; Guanghua Xiao; Eeva-Liisa Eskelinen; Philipp E. Scherer; Jennifer L. Whistler; Beth Levine
Cell | 2016
Rhea Sumpter; Shyam Sirasanagandla; Álvaro F. Fernández; Yongjie Wei; Xiaonan Dong; Luis H. Franco; Zhongju Zou; Christophe C. Marchal; Ming Yeh Lee; D. Wade Clapp; Helmut Hanenberg; Beth Levine
PMC | 2016
Rhea Sumpter; Shyam Sirasanagandla; Álvaro F. Fernández; Yongjie Wei; Xiaonan Dong; Luis H. Franco; Zhongju Zou; Christophe C. Marchal; Ming Yeh Lee; D. Wade Clapp; Helmut Hanenberg; Beth Levine
Autophagy, Infection, and the Immune Response | 2014
Xiaonan Dong; Beth Levine