Wu, Bin - Nanyang Technological University - School of Biological Sciences

个人简介

Education B.Sc. in Biological Sciences, 2002.07-2006.06, School of Biological Sciences, Nanyang Technological University, Singapore Ph.D. in Biochemistry, Biophysics and Structural Biology, 2006.07-2010.02, School of Biological Sciences, Nanyang Technological University, Singapore Professional Experience Nanyang Assistant Professor, School of Biological Sciences, NTU 2015.03-present Charles A. King Research fellow Harvard Medical School & Boston Children’s Hospital 2013.10-2015.02 GSK-IDI Research fellow Harvard Medical School 2010.02-2013.09

研究领域

Auto-immune Diseases, including a range of chronic conditions from mild Allergies and Arthritis (8-40% population), to more severe conditions like Crohn’s Disease and Systemic Lupus Erythomatosus (SLE, ~0.1% population), have become a increasing burden in developed countries, particularly in ageing societies. Despite the urgencies of the rising trend of Auto-immune Diseases, current treatments of such conditions are largely passive and only relieve the symptoms temporarily. Accumulating evidences suggested that an imbalanced innate immunity is the root of most of the symptoms. Understanding the regulatory mechanisms of the innate immunity will provide us with the right tools and knowledge to cure Auto-immune Diseases. Only until recent years, new discoveries and characterizations of a variety of cellular receptors have filled in the gaps of our understanding about how innate immunity works. These receptors are present in a wide range of cell types in human body, not only in specialized immune cells, capable of sensing almost all pathogens and initiating the defense mechanism. There are several classes of pathogen recognition receptors (PRRs), including the well-known Toll-like receptors (TLRs), and more recently characterized RIG-I like RNA helicases (RLRs), C-type lectin receptors (CLRs), NOD-like receptors (NLRs), and AIM-2 like receptors (ALRs). These PRRs target specific types of pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs). In many cases, PRRs have redundant and overlapping substrate specificities. Once activated, they will interact with their respective downstream signaling proteins called ‘adaptors’. Different pathways can often crosstalk with each other to initiate a robust and coordinated immune response. These sophisticated signal processing and amplification are usually carefully regulated at the adaptor level. A weakened cellular innate immune system will compromise the host’s function in effectively detecting and clearing the pathogens and maintaining health. However, a hyperactive or an imbalanced innate immune system contributes to undesirable autoimmune diseases. For example, in the case of Crohn’s disease, accumulating evidence suggest that mutations in several PRRs (including RLRs and NLRP3) result in the clinical symptoms. In these cases, the equilibrium among the immune system, the symbiotic microbes and the environmental factors is disrupted. In addition, mutations in MDA5 (a member of RLR) will result in elevated Interferon levels in patients and cause Aicardi-Goutieres Syndrome (AGS) and SLE. However, the detailed mechanisms of how to balance signals from multiple PRRs remain largely unclear, particularly the mechanism of activation threshold of these pathways, and the potential crosstalk and feedback between different signaling pathways. My research will focus on understanding these specific innate immune signaling pathways, with an ultimate goal of curing autoimmune diseases, using a combination of biochemical, structural and cellular approaches.

近期论文

查看导师最新文章（温馨提示：请注意重名现象，建议点开原文通过作者单位确认）

Wu B, Peisley A, Tetrault D, Li Z, Egelman EH, Magor K, Thomas Walz T, Penczek P, Hur S. Molecular imprinting as a signal activation mechanism of the viral RNA sensor RIG-I. Molecular Cell. 2014 Aug 21;55(4):511-23. PMID: 25018021 Peisley A, Wu B, Hui X, Chen ZJ and Hur S. Structural basis for ubiquitin-mediated antiviral signal activation by RIG-I. Nature. 2014 May 1; 509:110-114. PMID: 24590070 Peisley A*, Wu B*, Yao H, Walz T and Hur S. RIG-I forms signaling-competent filaments in an ATP-dependent and ubiquitin-independent manner. Molecular Cell. 2013 Sep 12;51(5):573-83. Wu B, Hur S. Viral counterattack against the host innate immune system. Cell Res. 2013 June, 23 (6), 735-736. Wu B, Peisley A, Richards C, Yao H, Zeng X, Lin C, Chu F, Walz T and Hur S. Structural Basis for dsRNA recognition, filament formation and antiviral signaling by MDA5. Cell. 2013 Jan 17;152(1-2):276-89. Peisley A*, Jo M*, Lin C, Wu B, Orme-Johnson M, Walz T, Hohng S & Hur S. Kinetic Mechanism for Viral dsRNA Length Discrimination by MDA5 Filament. U S AProc Natl Acad Sci U S A. 2012:109 (49): 19884-19885. Chua EY, Vasudevan D, Davey GE, Wu B, Davey CA. The mechanics behind DNA sequence-dependent properties of the nucleosome. Nucleic Acids Research. 2012;40(13):6338-52. Peisley A, Lin C, Wu B, Orme-Johnson M, Liu M, Walz T, Hur S. Cooperative assembly and dynamic disassembly of MDA5 filaments for viral dsRNA recognition. U S A.Proc Natl Acad Sci U S A. 2011:108(52):21010-5. Wu B, Davey GE, Nazarov A, Dyson PJ, Davey CA. Specific DNA structural attributes modulate platinum anticancer drug site selection and cross-link generation. Nucleic Acids Research. 2011;39(18):8200-12. Wu B, Ong MS, Groessl M, Adhireksan Z, Hartinger CG, Dyson PJ, Davey CA. A ruthenium antimetastasis agent forms specific histone protein adducts in the nucleosome core. Chemistry. 2011;17(13):3562-6. Wu B, Mohideen K, Vasudevan D, Davey CA. Structural insight into the sequence dependence of nucleosome positioning. Structure. 2010;18(4):528-36. Wu B, Davey CA. Using soft X-rays for a detailed picture of divalent metal binding in the nucleosome. Journal of Molecular Biology. 2010;398(5):633-40. Davey GE*, Wu B*, Dong Y, Surana U, Davey CA. DNA stretching in the nucleosome facilitates alkylation by an intercalating antitumour agent. Nucleic Acids Research. 2010;38(6):2081-8. Wu B, Davey CA. Platinum drug adduct formation in the nucleosome core alters nucleosome mobility butnot positioning. Chemistry & Biology. 2008 Oct 20;15(10):1023-8. PMID: 18940663. Wu B, Droge P, Davey CA. Site selectivity of platinum anticancer therapeutics. Nature Chemical Biology 2008;4(2):110-2. Profiled in “Research highlight.” Nature. 2008 Jan 10;451:111. PMID: 18157123.