Inflammasomes in Disease

Project Description

Inflammasome dysregulation drives pathology in a wide variety of human diseases (e.g. septic shock, gout, diabetes, neurodegenerative diseases, various cancers). We seek to understand the mechanisms by which inflammasomes drive human diseases, and use this knowledge to develop new inflammasome inhibitors.

 

Projects:

  • Mechanisms of inflammasome activation in disease
  • Pathological inflammasome functions in disease
  • New drugs to treat human inflammasome-driven diseases

 

Select Publications:

  1. Gordon R, Albornoz EA, Christie DC, Langley MR, Kumar V, Mantovani S, Robertson AAB, Butler MS, Rowe DB, O'Neill LA, Kanthasamy AG, Schroder K, Cooper MA, Woodruff TM (2018).
    Inflammasome inhibition prevents α-synuclein pathology and dopaminergic neurodegeneration in mice. Science Translational Medicine In press. Pubmed
     
  2. Hill JR, Coll RC, Sue N, Reid JC, Dou J, Holley CL, Pelingon R, Dickinson JB, Biden TJ, Schroder K, Cooper MA, Robertson AAB. (2017).
    Sulfonylureas as Concomitant Insulin Secretagogues and NLRP3 Inflammasome Inhibitors. Chem Med Chem Sep 7;12(17):1449-1457. Pubmed
     
  3. Mridha AR, Wree A, Robertson AA, Yeh MM, Johnson CD, Van Rooyen DM, Haczeyni F, Teoh NC, Savard C, Ioannou GN, Masters SL, Schroder K, Cooper MA, Feldstein AE, Farrell GC. (2017).
    NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice. Journal of Hepatology 2017 May;66(5):1037-1046. Pubmed
     
  4. Deuis JR, Yin K, Cooper MA, Schroder K, Vetter I. (2017).
    Role of NLRP3 inflammasome in a model of acute burn-induced pain. Burns Mar;43(2):304-309. Pubmed
     
  5. Masters SL, Lagou V, Jéru I, Baker PJ, Van Eyck L, Parry DA, Lawless D, De Nardo D, Garcia-Perez JE, Dagley LF, Holley CL, Dooley J, Moghaddas F, Pasciuto E, Jeandel PY, Sciot R, Lyras D, Webb AI, Nicholson SE, De Somer L, van Nieuwenhove E, Ruuth-Praz J, Copin B, Cochet E, Medlej-Hashim M, Megarbane A, Schroder K, Savic S, Goris A, Amselem S, Wouters C, Liston A (2016).
    Familial autoinflammation with neutrophilic dermatosis reveals a regulatory mechanism of pyrin activation. Science Translational Medicine Mar 30;8(332):332ra45. Pubmed
     
  6. Coll RC, Robertson AAB, Chae JJ, Higgins SC, Muñoz-Planillo R, Inserra MC, Vetter I, Dungan LS, Monks BG, Stutz A, Croker DE, Butler MS, Haneklaus M, Sutton CE, Núñez G, Latz E, Kastner DL, Mills KHG, Masters SL, Schroder K, Cooper MA, O’Neill LAJ (2015).
    A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nature Medicine 21(3):248-55. Pubmed
     
  7. Sester DP, Sagulenko V, Thygesen SJ, Cridland JA, Loi YS, Cridland SO, Masters SL, Genske U, Hornung V, Andoniou CE, Sweet MJ, Degli-Esposti MA, Schroder K, Stacey KJ (2015).
    Deficient NLRP3 and AIM2 Inflammasome Function in Autoimmune NZB Mice. Journal of Immunology 195(3):1233-41. Pubmed
     
  8. Zeis T, Allaman I, Gentner M, Schroder K, Tschopp J, Magistretti PJ, Schaeren-Wiemers N (2015).
    Metabolic gene expression changes in astrocytes in Multiple Sclerosis cerebral cortex are indicative of immune-mediated signaling. Brain, Behavior, Immunity 48:313-25. Pubmed
     
  9. Irvine KM, Schroder K, Powell EE (2012).
    Liver repercussions of defective gut surveillance. Hepatology 56: 1174-1177. Pubmed
     
  10. Schroder K, Zhou R, Tschopp J (2010).
    The NLRP3 inflammasome: a sensor for metabolic danger? Science 327: 296-300. Pubmed

 

Patents:

  1. O'Neill LA, Coll RC, Cooper MA, Robertson AAB, Schroder K. MacLeod AM, Miller DJ (2017).
    Sulfonylureas and related compounds and use of same. PCT/EP2017/053498, Filing: 16/02/2017.
     
  2. O'Neill LA, Coll RC, Cooper MA, Robertson AAB, Schroder K (2016).
    Sulfonylureas and related compounds and use of same. PCT/AU2016/050103, Filing: 16/02/2016.

 

Image: Artwork represents the role of inflammasomes in human disease. Diabetes is shown as an example.

Categories: 
Genetics
In vivo biology