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Dr Alison Condliffe

Dr Alison Condliffe

Alison Condliffe is accepting applications for PhD students.

Alison Condliffe is available for consultancy.


Research Interests

My research focuses on the role of neutrophil and eosinophil granulocytes as mediators of tissue injury in respiratory disease. I have a particular interest in the phenomenon of neutrophil priming, which increases potential of these cells to cause tissue injury and disease. My group also studies the effects of hypoxia (low oxygen levels) on granulocyte function, the mechanisms of glucocorticoid resistance in asthma, and the distribution and fate of eosinophils in health and in allergic disease as determined by novel imaging methodologies. One of my main clinical interests is the respiratory problems in primary immune deficiency, and this has led to a further major research initiative.

Both inflammatory cytokines such as GM-CSF, LPS, and TNFα, and also hypoxia, can lead to neutrophil priming. Primed neutrophils release approximately tenfold more reactive oxygen species and proteolytic enzymes such as neutrophil elastase when stimulated than do unprimed cells. We have shown that lipid second messengers generated by the phosphoinositide 3-hydroxykinase (PI3K) signaling system are critical in signaling the enhanced responses seen in primed cells, and in prolonging granulocyte lifespan in response to cytokines.

In collaboration with Dr Sergey Nejentsev (Department of Medicine), Dr Roger Williams (LMB), the Clinical Immunology Service (Addenbrooke’s Hospital), and with scientists at the Babraham Institute, I have identified and characterized a novel and severe immune deficiency syndrome termed ‘Activated PI3kinase delta Syndrome’ or APDS, that is caused by a a newly described autosomal dominant mutation in the gene coding for the catalytic subunit of PI3K delta. This mutation leads to increased constitutive and stimulated activity of this key signaling enzyme, and we are currently investigating precisely how this results in the very profound susceptibility to bacterial and viral infection that we see in the patients.

Ongoing projects in the laboratory include the effects of hypoxia on granulocyte signaling pathways, the role of hypoxia in glucocorticoid resistance, and the role of the PI3K pathway in immune dysfunction both in general, and in APDS in particular.

Group members:
Linsey Porter
Rosalind Simmonds
 

Keywords

eosinophils ; granulocytes ; hypoxia ; traffic ; neutrophils

Topics

  • Bronchiectasis
  • asthma
  • rheumatoid arthritis
  • arthritis
  • immunodeficiency
  • respiratory disease

Key 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 E, Cant AJ, Kumararatne D, Okkenhaug K, Williams RL, Condliffe A*, Nejentsev S*. Phosphoinositide 3-Kinase δ Gene Mutation Predisposes to Respiratory Infection and Airway Damage. Science. 2013 Oct 17. *shared senior authors

Juss JK, Hayhoe RP, Owen CE, Bruce I, Walmsley SR, Cowburn AS, Kulkarni S, Boyle KB, Stephens L, Hawkins PT, Chilvers ER, Condliffe AM. Functional Redundancy of Class I Phosphoinositide 3-Kinase (PI3K) Isoforms in Signaling Growth Factor-Mediated Human Neutrophil Survival. PLoS One. 2012;7(9):e45933.

Farahi N, Singh NR, Heard S, Loutsios C, Summers C, Solanki CK, Solanki K, Balan KK, Ruparelia P, Peters AM, Condliffe AM, Chilvers ER. Use of 111-Indium-labelled autologous eosinophils to establish the in vivo kinetics of human eosinophils in healthy subjects. Blood. 2012 Sep 19.

Wilczynska MM, Condliffe AM, McKeon DJ. Coexistence of Bronchiectasis and Rheumatoid Arthritis: Revisited. Respir Care. 2012 Jul 10.

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. Effects of the cyclin-dependent kinase inhibitor R-roscovitine on eosinophil survival and clearance. Clin Exp Allergy. 2011 May;41(5):673-87.

McGovern NN, Cowburn AS, Porter L, Walmsley SR, Summers C, Thompson AA, Anwar S, Willcocks LC, Whyte MK, Chilvers ER,* Condliffe AM.* Hypoxia selectively inhibits respiratory burst activity and killing of Staphylococcus aureus in human neutrophils. J Immunol 2011;186(1):453-63. *joint senior author

Condliffe AM*, Suire S*, Ferguson GJ, Ellson CD, Guillou H, Davidson K, Welch H, Coadwell J, Turner M, Chilvers ER, Hawkins PT, Stephens L. Gbetagammas and the Ras binding domain of p110gamma are both important regulators of PI(3)Kgamma signalling in neutrophils. Nat Cell Biol 2006; 8:1303-9. * Joint first authors.

 

Neutrophils (black arrow)

Eosinophils (white arrow)