Inflammasomes are assembled by innate immune receptor proteins (e.g. Nod-like receptors) but the underlying molecular mechanisms are largely unknown. We seek to understand how inflammasome scaffolds sense cellular ‘danger’ signals, and nucleate the formation of inflammasome complexes.

Projects:

• Mechanisms of NLRP3 activation
• Molecular determinants of inflammasome assembly

Select Publications:

1. Coll RC, Hill JR, Day CJ, Zamoshnikova A, Boucher D, Massey NL, Chitty JL, Fraser JA, Jennings MP, Robertson AAB, Schroder K (2019).
   MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition. Nature Chemical Biology 15(6):556-559. PDF Pubmed
    
2. Boucher D, Monteleone M¹, Coll RC¹, Chen KW¹, Ross CM, Teo JL, Gomez GA, Holley CL, Bierschenk D, Stacey KJ, Yap AS, Bezbradica JS and Schroder K. (2018).
   Caspase-1 self-cleavage is an intrinsic mechanism to terminate inflammasome activity. Journal of Experimental Medicine 215(3):827-840. ¹Joint contribution. Pubmed
    
3. Bezbradica JS¹, Coll R¹, Schroder K (2017).
   Sterile signals generate weaker and delayed macrophage NLRP3 inflammasome responses relative to microbial signals. Cellular & Molecular Immunology. 14:118-126. ¹Joint contribution. Pubmed
    
4. Chen KW, Bezbradica JS, Gross CJ, Wall AA, Sweet MJ, Stow JL, Schroder K (2016).
   The murine neutrophil NLRP3 inflammasome is activated by soluble but not particulate or crystalline agonists. European Journal of Immunology 46(4):1004-10. Pubmed
    
5. Groß CJ, Mishra R, Schneider KS, Médard G, Wettmarshausen J, Dittlein DC, Shi H, Gorka O, Koenig PA, Fromm S, Magnani G, Ćiković T, Hartjes L, Smollich J, Robertson AA, Cooper MA, Schmidt-Supprian M, Schuster M, Schroder K, Broz P, Traidl-Hoffmann C, Beutler B, Kuster B, Ruland J, Schneider S, Perocchi F, Groß O. (2016).
   K+ Efflux-Independent NLRP3 Inflammasome Activation by Small Molecules Targeting  Mitochondria. Immunity. Oct 18;45(4):761-773. Pubmed
    
6. Baker PJ¹, Boucher D¹, Bierschenk D, Tebartz C, Whitney PG, D'Silva DB, Tanzer MC, Monteleone M, Robertson AA, Cooper MA, Alvarez-Diaz S, Herold MJ, Bedoui S, Schroder K^2, Masters SL² (2015).
   NLRP3 inflammasome activation downstream of cytoplasmic LPS recognition by both caspase-4 and caspase-5. European Journal of Immunology 45:2918-26. ^{1, 2}Joint Contribution. Pubmed
    
7. Guarda G, Zenger M, Yazdi AS, Schroder K, Ferrero I, Menu P, Tardivel A, Mattmann C, & Tschopp J (2011).
   Differential expression of NLRP3 among hematopoietic cells. Journal of Immunology 186(4):2529-2534. Pubmed
    
8. Schroder K, Zhou R, & Tschopp J (2010).
   The NLRP3 inflammasome: a sensor for metabolic danger? Science 327(5963):296-300. Pubmed
    
9. Tschopp J & Schroder K (2010).
   NLRP3 inflammasome activation: The convergence of multiple signalling pathways on ROS production? Nature Reviews Immunology 10(3):210-215. Pubmed
    
10. Schroder K, Muruve DA, & Tschopp J (2009).
    Innate immunity: cytoplasmic DNA sensing by the AIM2 inflammasome. Current Biology 19(6):R262-265. Pubmed

Image: Artwork represents an activated inflammasome.