Hao Wu, Ph.D.

Hao Wu, Ph.D.

Asa and Patricia Springer Professor, Department of Biological Chemistry and Molecular Pharmacology
Department of Pediatrics, Harvard Medical School
Senior Investigator, Program in Cellular and Molecular Medicine, Boston Children’s Hospital
Hao Wu, Ph.D.

The Wu laboratory of structural immunology focuses on elucidating the molecular mechanism of signal transduction by immune receptors, especially innate immune receptors.

Research Interests:

The Wu laboratory of structural immunology focuses on elucidating the molecular mechanism of signal transduction by immune receptors, especially innate immune receptors. The lab began its studies on the signaling of a classical cytokine produced by the innate immune system, tumor necrosis factor (TNF), which induces diverse cellular responses such as NF-κB activation and cell death. Receptors for TNF belong to the large TNF receptor (TNFR) superfamily. The second pursuit of the lab has been the Toll-like receptor (TLR)/interleukin-1 receptor (IL-1R) superfamily, which induces signaling pathways overlapping with those of the TNFR superfamily. TLRs are transmembrane receptors that sense a discrete collection of molecules of microbial origin in the extracellular space and endosomes and members of IL-1R family are receptors for cytokines IL-1 and IL-18. TLRs and IL-1Rs share similar cytoplasmic domains. The lab recently expanded its research to a number of cytosolic pattern recognition receptors that provide intracellular surveillance of infections. Some of these intracellular sensors can induce pathways overlapping with those of TLRs such as activation of NF-κB and interferon regulatory factors. Others mediate the formation of inflammasomes that control activation of caspase-1, which in turn regulates maturation of the proinflammatory cytokines IL-1 and IL-18 and induces pyroptosis, a rapid inflammatory form of cell death.  

The overall objective of the Wu lab has been to determine how macromolecular interactions mediate the transmission of signals from receptors to effectors to direct innate immune responses using the core approaches of structural biology. These structural studies challenge the traditional view of signal transduction as a string of recruitment and allosteric events. As a recurrent theme, the lab’s research revealed that upon ligand stimulation, many innate immune receptors assemble large oligomeric intracellular signaling complexes, or “signalosomes” to induce the activation of caspases, kinases and ubiquitin ligases, leading to cell death, cytokine maturation or expression of gene products for immune and inflammatory responses. The different scaffolds identified by these structural studies provide a molecular foundation for understanding the formation of microscopically visible signaling clusters in cells.

Selected Publications:

Lu A, Magupalli VG, Ruan J, Yin Q, Atianand MK, Vos MR, Schröder GF, Fitzgerald KA, Wu H*, Egelman EH (2014). Unified Polymerization Mechanism for the Assembly of ASC-Dependent Inflammasomes. Cell. 6: 1193-206. *Corresponding author

 Qiao Q, Yang C, Zheng C, Fontan L, David L, Yu X, Bracken C, Rosen M, Melnick A, Egelman E, Wu H (2013) Structural Architecture of the CARMA1/Bcl10/MALT1 Signalosome: Nucleation-Induced Filamentous Assembly. Mol Cell. 51:766-779

 Yin Q, Sester DP, Tian Y, Hsiao YS, Lu A, Cridlan JA, Sagulenko V, Thygesen SJ, Chouhey D, Hornung V, Walz T, Stacey KJ, Wu H (2013). Molecular Mechanism for p202-mediated Specific Inhibition of AIM2 Inflammasome Activation. Cell Reports 4: 327-39

 Wu H (2013). Higher-Order Assemblies in a New Paradigm of Signal Transduction Cell 153: 287-292

Jixi Li, Thomas McQuade, Ansgar B. Siemer, Johanna Napetschnig, Kenta Moriwaki, Yu-Shan Hsiao, Ermelinda Damko, David Moquin, Thomas Walz, Ann McDermott, Francis Ka-Ming Chan, and Hao Wu (2012). The RIP1/RIP3 necrosome forms a functional amyloidal signaling complex required for programmed necrosis. Cell, 150: 339-350. 

Contact Information

Immune Disease Institute,
Center for Life Sciences Building
3 Blackfan Circle, 3rd Floor, Room 3099
Boston, MA 02115
p: 617 713-8160 f: 617 713-8161

Faculty Alphabetical