Research
My principal research interest is to understand the precise molecular signaling mechanisms underlying neutrophil (PMN) dysregulation in acute respiratory distress syndrome (ARDS). I am using a panel of novel small molecule PI3K class I isoform selective inhibitors to define the precise roles of individual PI3K isoforms on constitutive and modulated PMN apoptosis rates and their impact on downstream signalling pathways.
There is emerging evidence for the existence of functionally distinct PMN subpopulations with pro- or anti-inflammatory properties. I am developing methodologies to consistently identify/isolate PMN subtypes in order to delineate their precise functional capacity (i.e. oxidative burst, phagocytosis, NET production, adaptive immune function and bioenergetic/ lipidomic profiles) and define the downstream effector pathways regulating these functions.
These studies will inform our understanding of the role of PMN subtypes in innate and adaptive immunity and aid development of novel therapeutic strategies designed to limit the extent and duration of neutrophil-dominated inflammation without compromising host immunity.
Publications
Angulo I, Vadas O, Garçon F, Banham-Hall E, Plagnol V, Leahy TR, Baxendale H, Coulter T, Curtis J, Wu C, Blake-Palmer K, Perisic O, Smyth D, Maes M, Fiddler C, Juss J, Cilliers D, Markelj G, Chandra A, Farmer G, Kielkowska A, Clark J, Kracker S, Debré M, Picard C, Pellier I, Jabado N, Morris JA, Barcenas-Morales G, Fischer A, Stephens L, Hawkins P, Barrett JC, Abinun M, Clatworthy M, Durandy A, Doffinger R, Chilvers ER, Cant AJ, Kumararatne D, Okkenhaug K, Williams RL, Condliffe A, Nejentsev S. (2013 ) Phosphoinositide 3-kinase δ gene mutation predisposes to respiratory infection and airway damage.
Science. 342(6160):866-71.
Juss JK, Hayhoe RP, Owen CE, Bruce I, Walmsley SR, Cowburn AS, Kulkarni S, Boyle KB, Stephens L, Hawkins PT, Chilvers ER, Condliffe AM. (2012) Functional Redundancy of Class I Phosphoinositide 3-Kinase (PI3K) Isoforms in Signaling Growth Factor-Mediated Human Neutrophil Survival. PLoS One. 7(9):e45933.
Kulkarni S, Sitaru C, Jakus Z, Anderson KE, Damoulakis G, Davidson K, Hirose M, Juss J, Oxley D, Chessa TA, Ramadani F, Guillou H, Segonds-Pichon A, Fritsch A, Jarvis GE, Okkenhaug K, Ludwig R, Zillikens D, Mocsai A, Vanhaesebroeck B, Stephens LR, Hawkins PT. PI3Kβ plays a critical role in neutrophil activation by immune complexes.
Science Signalling. 2011; 4(168):ra23.
Farahi N, Uller L, Juss JK, Langton AJ, Cowburn AS, Gibson A, Foster MR, Farrow SN, Marco-Casanova P, Sobolewski A, Condliffe AM, Chilvers ER. (2011) Effects of the cyclin-dependent kinase inhibitor R-roscovitine on eosinophil survival and clearance. Clin Exp Allergy. 41(5):673-87.
Brode S, Farahi N, Cowburn AS, Juss JK, Condliffe AM, Chilvers ER. (2010) Interleukin-5 inhibits glucocorticoid-mediated apoptosis in human eosinophils.Thorax. 65(12):1116-7.
