Hierarchy of higher order assemblies in immunity is a relatively fresh concept, which states that only upstream molecules can trigger the assembly of downstream molecules. This leads to a tightly regulated “all-or-none” response in the cell , which is characteristic for immune pathways, and provide protection against malignant cells. Therefore, “mistakes” in immune pathways may result in tumor cells escaping immune surveillance and elimination. Additionally, dysregulation of immune pathways, for example of proteins involved in T and B lymphocyte signaling and inflammatory pathways, may result in inflammatory environment beneficial for the survival of malignant cells and therefore cancer development and propagation. The lab is aimed to mechanistically elucidate molecular pathways in immunity and cancer that require the formation of high-order assemblies by combining cutting edge techniques in biochemistry, structural biology (crystallography & cryo-EM microscopy) and cell biology including live cell imaging and super-resolution microscopy.

David L, Borges LP, Hollingsworth LR, Volchuck A, Jansen I, Steinberg BE, Wu H. NINJ1 mediates plasma membrane rupture through formation of nanodiscs-like rings. Biorxiv 2023. 2. Du G*, Healy L*, David L#, Walker C, Fontana P, Dong Y, Devant P, Puthenveetil R, Ficarro S, Banerjee A, Kagan J, Lieberman J, Wu H#. ROS-dependent palmitoylation is an obligate licensing signal for GSDMD pore formation. Biorxiv 2023. * Contributed equally, # co-corresponding author

David L#, Fuentes L, Xi Q, Kooshesh K, Zhang Y, Shah VJ, Wu H# and Maas RL#. Piezo Mechanosensory channels regulate centrosome integrity and mitotic entry. Proc Natl Acad Sci U S A Jan 3, 120(1) (2023). 2. Xia M*, David L*, Teater. M, Gutierrez. J, Wang. X, Meydan. C, Onder. O, Elenitoba-Johnson. K, Zamponi. N. Cerchietti, Lu. TB, Philippar. U, Fontan L, Wu H, Melnick AM. BCL10 mutations define distinct dependencies guiding precision therapy for DLBCL. Cancer Discov (12:1-20) (2022).

Andreeva L, David L, Rawson. S, Shen. C, Pasricha. T, Pelegrin. P, Wu. H NLRP3 cages revealed by full-length mouse NLRP3 structure control pathway activation. Cell 184:6299-6312 (2021). 4. Hollingsworth LR*, David L*, Li Y*, Griswold AR, Ruan J, Sharif H, Fontana P, Orth-He EL, Fu T, Bachovchin DA & Wu H. Novel mode of filament formation in UPA-promoted CARD8 and NLRP1 Inflammasomes. Nat Commun (12(1):189) (2021).

Hauseman ZJ, Harvey EP, Newman CE, Wales TE, Bucci JC, Mintseris J, Schweppe DK, David L, Fan L, Cohen DT, Herce HD, Mourtada R, Ben-Nun Y, Bloch NB, Hansen SB, Wu H, Gygi SP, Engen JR, Walensky LD. Homogeneous Oligomers of Pro-apoptotic BAX Revels Structural Determination of Mitochondrial Membrane Permeabilization. 6. Stinson JR, Dorjbal B, McDaniel DP, David L, Wu H, Snow AL. Gain-of-function mutations in CARD11 promotes enhanced aggregation and idiosyncratic signalosome assembly. Cell Immunol (353:104129) (2020). 7. David L., Li, Y., Ma. J., Zhang, X., Garner E. and Wu H. Assembly mechanism of the CARMA1-BCL10- MALT1-TRAF6 signalosome. Proc Natl Acad Sci U S A, 115:1499-1504 (2018).

Zhang L, Chen S, Ruan J, Wu J, Yin Q, Li Y, David L, Lu A, Wang W, Marks C, Ouyang Q, Zhang X, Mao Y and Wu H. Cryo-EM Structure of the Activated PrgJ/NAIP2/NLRC4 Inflammasome reveals nucleated polymerization. Science, 350:404-9 (2015). 9. Qiao Q, Yang C, Zheng C, Fontán L, David L, Yu X, Bracken C, Rosen M, Melnick A, Egelman EH, Wu H. Structural Architecture of the CARMA1/Bcl10/MALT1 Signalosome: Nucleation Induced Filamentous Assembly. Mol Cell, 26;51(6):766-79 (2013).

Technion, Israel Institute of Technology, 2012