Immunology Faculty Member - Hao Wu, PhD

Hao Wu, PhD

Harvard Medical School
Boston Children's Hospital
3 Blackfan Circle, CLSB, Room 3099
Boston, MA 02115
Tel: 617-713-8160
Fax: 617-713-8161

The Wu laboratory of structural immunology focuses on elucidating the molecular mechanism of signal transduction by immune receptors, especially innate immune receptors with a current focus on inflammasomes. The lab began its studies on the tumor necrosis factor (TNF) receptor superfamily and the Toll-like receptor (TLR)/interleukin-1 receptor (IL-1R) superfamily for their diverse cellular responses such as NF-κB activation and cell death. Inflammasomes are cytosolic supramolecular complexes that activate caspase-1 and other inflammatory caspases such as mouse caspase-11, and human caspase-4 and -5. They provide intracellular surveillance of infections and other types of danger, and alert the immune system by inducing the maturation of the proinflammatory cytokines IL-1 and IL-18 and pyroptosis, a rapid inflammatory form of cell death. We recently discovered that the downstream effector gasdermin D (GSDMD) of inflammasomes forms large pores on cells to promote cytokine secretion and 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.

Last Update: 6/20/2018


Qian Yin, David P. Sester, Yuan Tian, Yu-Shan Hsiao, Alvin Lu, Jasmyn A. Cridlan, Vitaliya Sagulenko, Sara J. Thygesen, Divaker Choubey, Veit Hornung, Thomas Walz, Katryn J. Stacey, and Hao Wu (2013). Molecular Mechanism for p202-mediated Specific Inhibition of AIM2 Inflammasome Activation. Cell Reports 4: 327-39

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

Yin Q, Tian Y, Kabaleeswaran V, Jiang X, Tu D, Eck MJ, Chen ZJ,
Wu H (2012). Cyclic di-GMP sensing via the innate immune signaling protein STING. Mol Cell 46: 735-45

Fontan L, Yang C, Kabaleeswaran V, Volpon L, Osborne MJ, Beltran E, Garcia M, Cerchietti L, Shaknovich R, Yang SN, Fang F, Gascoyne RD, Martinez-Climent JA, Glickman JF, Borden K,
Wu H, Melnick A (2012). MALT1 Small Molecule Inhibitors Specifically Suppress ABC-DLBCL In Vitro and In Vivo. Cancer Cell 22: 812-24

Li J, McQuade T, Siemer AB, Napetschnig J, Moriwaki K, Hsiao YS, Damko E, Moquin D, Walz T, McDermott A, Chan FK,
Wu H (2012). The RIP1/RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis. Cell 150: 339-50

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