Dr. Hao Wu

Biography

Wu laboratory of structural immunology focuses on elucidating the molecular mechanisms of signal transduction in immune receptors, particularly innate immune receptors. The lab studies the signaling of the classical cytokine tumor necrosis factor (TNF), which induces diverse cellular responses through NF-κB activation and cell death. TNF receptors belong to the large TNF receptor (TNFR) superfamily. The lab's research has expanded to include Toll-like receptor (TLR)/interleukin-1 receptor (IL-1R) superfamily receptors, which induce signaling pathways that overlap with those of the TNFR superfamily. TLRs are transmembrane receptors that sense a discrete collection of molecules of microbial origin present in the extracellular space and endosomes. The lab has recently begun investigating a number of cytosolic pattern recognition receptors that provide intracellular surveillance against infections. These intracellular sensors induce pathways that overlap with TLRs, activating NF-κB and interferon regulatory factors. This research mediates the formation of inflammasomes that control the activation of caspase-1, which regulates the maturation of proinflammatory cytokines IL-1 and IL-18 and induces pyroptosis, a rapid inflammatory form of cell death. The overall objective of the Wu lab is to determine the macromolecular interactions that mediate transmission of signals from receptors to effectors that direct innate immune responses, using core approaches in structural biology. The structural studies challenge the traditional view of signal transduction as a linear recruitment process and highlight the allosteric events involved. A recurrent theme in the lab's research is the observation that ligand stimulation leads to the assembly of large oligomeric intracellular signaling complexes, referred to as 'signalosomes,' which induce the activation of caspases, kinases, and ubiquitin ligases, thereby influencing cell death, cytokine maturation, and the expression of gene products involved in immune and inflammatory responses. The scaffolds identified through structural studies provide a molecular foundation for understanding the formation of microscopically visible signaling clusters within cells.

Research Interests