Hao Wu

Hao Wu

Professor of Biological Chemistry and Molecular Pharmacology; Professor of Pediatrics

Boston Children's Hospital
Clsb-3098
3 Blackfan Circle
Boston, MA 02115
Tel: 617-713-8160
Email: hao.wu@childrens.harvard.edu

Website: wulab.tch.harvard.edu 
Lab Size: Between 15 and 20

Summary

The Wu laboratory of structural and mechanistic immunology focuses on elucidating the molecular and cellular mechanisms that govern the assembly, regulation and therapeutic intervention of supramolecular complexes in innate immunity. Our current research focuses on inflammasomes, which are cellular machineries for activating inflammatory caspases. Activated caspases process the IL-1 family cytokines and the pore forming protein gasdermin D (GSDMD), and GSDMD pores release the mature cytokines and cause pyroptotic cell death. We also have ongoing projects on mechanism and therapeutic intervention in tumor necrosis factor (TNF) and Toll-like receptor (TLR) signaling pathways.

There are three pillars for the research in the lab, 1) cryo-EM, condensate or phase separation assays, and other biophysical methods for detailed understanding of molecular complexes, including a large number of membrane proteins, 2) drug screening and validation for potential therapeutics in immune diseases and cancer, and 3) cellular imaging and other tools for the assembly of supramolecular complexes in cells.

Publications

Fontana P, Du G, Zhang Y, Zhang H, Vora SM, Hu JJ, Shi M, Tufan AB, Healy LB, Xia S, Lee DJ, Li Z, Baldominos P, Ru H, Luo HR, Agudo J, Lieberman J, Wu H. Small-molecule GSDMD agonism in tumors stimulates antitumor immunity without toxicity. Cell. 2024 Sep 2:S0092-8674(24)00898-5. doi: 10.1016/j.cell.2024.08.007. Epub ahead of print. PMID: 39243763.

David L, Borges JP, Hollingsworth LR, Volchuk A, Jansen I, Garlick E, Steinberg BE, Wu H. NINJ1 mediates plasma membrane rupture by cutting and releasing membrane disks. Cell. 2024 Apr 25;187(9):2224-2235.e16. doi: 10.1016/j.cell.2024.03.008. Epub 2024 Apr 12. PMID: 38614101.

Dong Y, Bonin JP, Devant P, Liang Z, Sever AIM, Mintseris J, Aramini JM, Du G, Gygi SP, Kagan JC, Kay LE, Wu H. Structural transitions enable interleukin-18 maturation and signaling. Immunity. 2024 Jul 9;57(7):1533-1548.e10. doi: 10.1016/j.immuni.2024.04.015. Epub 2024 May 10. PMID: 38733997.

Du G, Healy LB, David L, Walker C, El-Baba TJ, Lutomski CA, Goh B, Gu B, Pi X, Devant P, Fontana P, Dong Y, Ma X, Miao R, Balasubramanian A, Puthenveetil R, Banerjee A, Luo HR, Kagan JC, Oh SF, Robinson CV, Lieberman J, Wu H. ROS-dependent S-palmitoylation activates cleaved and intact gasdermin D. Nature. 2024 Jun;630(8016):437-446. doi: 10.1038/s41586-024-07373-5. Epub 2024 Apr 10. PMID: 38599239.

Devant P, Dong Y, Mintseris J, Ma W, Gygi SP, Wu H, Kagan JC. Structural insights into cytokine cleavage by inflammatory caspase-4. Nature. 2023 Dec;624(7991):451-459. doi: 10.1038/s41586-023-06751-9. Epub 2023 Nov 22. Erratum in: Nature. 2024 Jan;625(7995):E17. doi: 10.1038/s41586-023-06942-4. PMID: 37993712.

Xiao L, Magupalli VG, Wu H. Cryo-EM structures of the active NLRP3 inflammasome disc. Nature. 2023 Jan;613(7944):595-600. doi: 10.1038/s41586-022-05570-8. Epub 2022 Nov 28. PMID: 36442502.

Dong Y, Pi X, Bartels-Burgahn F, Saltukoglu D, Liang Z, Yang J, Alt FW, Reth M, Wu H. Structural principles of B cell antigen receptor assembly. Nature. 2022 Dec;612(7938):156-161. doi: 10.1038/s41586-022-05412-7. Epub 2022 Oct 13. PMID: 36228656.

Fontana P, Dong Y, Pi X, Tong AB, Hecksel CW, Wang L, Fu TM, Bustamante C, Wu H. Structure of cytoplasmic ring of nuclear pore complex by integrative cryo-EM and AlphaFold. Science. 2022 Jun 10;376(6598):eabm9326. doi: 10.1126/science.abm9326. Epub 2022 Jun 10. PMID: 35679401.