Boston Children's Hospital
Center for Life Science Building, Room 3095
3 Blackfan Circle
Boston, MA 02215
The ability to distinguish “self” from “non-self” is fundamental to proper functioning of both the innate and adaptive immune systems. Several pattern recognition receptors (PRR) in the innate immune system are responsible for the initial detection of foreign molecules associated with pathogens such as bacterial cell wall components or viral nucleic acids. We are particularly interested in how PRRs efficiently and accurately discriminate between self and non-self RNAs that are made up of identical building blocks. It was traditionally believed that dsRNA structures, which are often present in viral RNAs, provide sufficient means for PRRs to selectively recognize viral RNAs against the background of cellular RNAs. However, accumulating evidence suggests that the mechanism for viral RNA detection is more complex than a simple duplex binding, and understanding the molecular mechanism would require more detailed structural and biochemical dissection at the level of both ligand-receptor as well as receptor-signaling adaptor interactions. Our lab uses a combination of crystallography, computational modeling and a variety of biochemical and biophysical methods to determine the structures, dynamics and functions of these receptors in isolation, in complex with RNAs and in higher order complexes with functional partners in the signaling pathway.
Peisley A*, Wu B*, Yao H, Walz T & Hur S. RIG-I forms signaling-competent filaments in an ATP-dependent and ubiquitin-independent manner. Molecular Cell, 2013, 51, 573-83, PMID: 23993742
Wu B and Hur S. Viral counterattack against the host innate immune system. Cell Research, 2013, 23, 735-6, PMID:23478300
Wu B, Peisley A, Richards C, Yao H, Zeng Z, Lin C, Chu F, Walz T & Hur S. Structural Basis for dsRNA recognition, filament formation and antiviral signaling by MDA5. Cell, 2013, 152, 276-89, PMID: 23273991
Feng Q, Hato SV, Langereis MA, Zoll J, Virgen-Slane R, Peisley A, Hur S, Semler BL, van Rij R & van Kuppeveld FJM. MDA5 detects the double-stranded RNA replicative form in picornavirus-infected cells, Cell Reports, (2012), 2, 1187-96, PMID:23142662
Peisley A*, Jo MH*, Lin C, Wu B, Orme-Johnson M, Walz T, Hohng S & Hur S. Kinetic Mechanism for Viral dsRNA Length Discrimination by MDA5 filament. Proc. Natl. Acad. Sci. U.S.A. (2012), 109, E3340-9, PMID:23129641 (* equal contribution)
Peisley A & Hur S. Multi-level regulation of cellular recognition of viral dsRNA. Cell Mol. Life Sci. (2013), 70, 1949-63, PMID:22960755
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. Proc. Natl. Acad. Sci. U.S.A. (2011), 108, 21010-5.
Last Update: 1/6/2014