Hao Wu’s research focuses on elucidating the molecular mechanism of signal transduction by immune receptors, especially innate immune receptors, using core approaches of structural biology. Her contributions began in the TNF receptor pathway, which is inappropriately activated in autoimmune states. Dr Wu’s laboratory has elucidated precise structural bases for how TNF signaling occurs and, thereby, provided rational understandings on anti-TNF therapies, the most effective treatments for these conditions. Dr Wu has also elucidated the structural basis for signal transduction of the pro-inflammatory interleukin-1 receptor (IL-1R) family and the Toll-like receptor (TLR) family, which share a set of overlapping cytoplasmic signaling proteins with the TNF receptor family. Most recently, her laboratory performed structural studies on NLRP3, AIM2, NLRC4 and NLRP6 inflammasomes, which are supramolecular complexes that activate inflammatory caspases such as caspae-1. Her studies further revealed how gasdermin D (GSDMD), which is the downstream effector cleaved by inflammatory caspases, leads to membrane pore formation, cytokine release and pyroptotic cell death.
Dr Wu’s structural studies challenge the traditional view of signal transduction as a string of recruitment and allosteric events. As a recurrent theme, Dr Wu observed 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. A number of different scaffolds, including a helical scaffold by members of the death domain family, have been identified from these structural studies, which provide a molecular foundation for understanding the formation of microscopically visible signaling clusters in cells.
Dr Wu received her pre-medical training in Peking University from 1982 to 1985 and studied Medicine at Peking Union Medical College from 1985 to 1988. She obtained her PhD in Biochemistry from Purdue University in 1992 as an HHMI predoctoral fellow. After performing postdoctoral research at Columbia University as an Aaron Diamond Foundation Fellow, Dr Wu started her faculty appointment at Weill Cornell Medical College in 1997 and was promoted to Professor in 2003. In 2012, Dr Wu became the Asa and Patricia Springer Professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School and Boston Children’s Hospital.
Dr Wu received a number of honors including Pew Scholar Award, Rita Allen Scholar Award, New York Mayor’s Award for Excellence in Science and Technology, Biophysical Society Margaret Dayhoff Memorial Award, Protein Society Dorothy Crowfoot Hodgkin Award, International Cytokine and Interferon Society Seymour & Vivian Milstein Award, and Biophysical Society Fellows Award. She serves on the Scientific Advisory Council of Cancer Research Institute and the Editorial Board of Cancer Cell, and has been an elected member of the National Academy of Sciences since 2015.