Caspase Activation and Cellular Programs

Project Description

Inflammasomes activate caspase family proteases, and thereby trigger caspase-dependent cellular programs, such as cytokine maturation and secretion, pyroptotic cell death and apoptotic cell death. We aim to understand precisely how inflammasomes control the activity of inflammatory caspases, and the proteolytic cascades that control cellular programs such as pyroptotic cell death and unconventional protein secretion.

 

Projects:

  • Mechanisms of inflammatory caspase activation and deactivation
  • Caspase-1-dependent unconventional protein secretion

 

Select Publications:

  1. Chan AH, Schroder K. (2020).
    Inflammasome signaling and regulation of interleukin-1 family cytokines. Journal of Experimental Medicine. 2020 Jan 6;217(1). pii: e20190314. doi: 10.1084/jem.20190314. PubMed PMID: 31611248. Pubmed
     
  2. Ross C, Chan AH, Von Pein J, Boucher D, Schroder K (2018).
    Dimerization and auto-processing induce caspase-11 protease activation within the non-canonical inflammasome. Life Science Alliance ADec 6;1(6):e201800237. Pubmed
     
  3. Chen KW1, Monteleone M1, Boucher D1, Sollberger G, Ramnath D, Condon ND, von Pein JB, Broz P, Sweet MJ, Schroder K. (2018).
    Noncanonical inflammasome signaling elicits gasdermin D-dependent neutrophil extracellular traps. Science Immunology Aug 24;3(26). pii: eaar6676. 1Joint contribution. Pubmed
     
  4. Monteleone M, Stanley AC, Chen KW, Brown DL, Bezbradica JS, von Pein JB, Holley CL, Boucher D, Shakespear MR, Kapetanovic R, Rolfes V, Sweet MJ, Stow JL, Schroder K. (2018).
    Interleukin-1β Maturation Triggers Its Relocation to the Plasma Membrane for Gasdermin-D-Dependent and -Independent Secretion. Cell Reports Aug 7;24(6):1425-1433. Pubmed
     
  5. 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
     
  6. Chen KW, Lawlor KE, von Pein JB, Boucher D, Gerlic M, Croker BA, Bezbradica J, Vince JE, Schroder K. (2018).
    IAP inhibition sensitizes neutrophils to TNF but not LPS-mediated cell death and IL-1β secretion. Journal of Immunology In press. Pubmed
     
  7. Boucher D, Chan A, Ross C, Schroder K. (2018).
    Quantifying Caspase-1 Activity in Murine Macrophages. Methods in Molecular Biology 1725:163-176. Pubmed
     
  8. 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 K2, 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, 2Joint Contribution. Pubmed
     
  9. Monteleone M, Stow JL, & Schroder K (2015).
    Mechanisms of unconventional secretion of IL-1 family cytokines. Cytokine 74(2):213-218. Pubmed
     
  10. Boucher D, Chen KW, & Schroder K (2015).
    Burn the house, save the day: pyroptosis in pathogen restriction. Inflammasome 2(1):1-6. Inflammasome
     
  11. Chen KW, Gross CJ, Sotomayor FV, Stacey KJ, Tschopp J, Sweet MJ, & Schroder K (2014).
    The neutrophil NLRC4 inflammasome selectively promotes IL-1beta maturation without pyroptosis during acute Salmonella challenge. Cell Reports 8(2):570-582. Pubmed
     
  12. Sagulenko V, Thygesen SJ, Sester DP, Idris A, Cridland JA, Vajjhala PR, Roberts TL, Schroder K, Vince JE, Hill JM, Silke J, & Stacey KJ (2013).
    AIM2 and NLRP3 inflammasomes activate both apoptotic and pyroptotic death pathways via ASC. Cell Death and Differentiation 20(9):1149-1160. Pubmed
     
  13. Schroder K & Tschopp J (2010).
    The inflammasomes. Cell 140(6):821-832. Pubmed

 

Image: Three-dimensional protein structures of the Caspase1 dimer. Image credit: Image generated in pymol by Dr Dave Boucher, using the 1ICE structure from the Protein Data Bank.

Categories: 
Molecular biology
Cell biology