Professor Alison Condliffe
Professor of Respiratory Medicine
& Deputy Head of Department
Department of Infection, Immunity & Cardiovascular Disease
University of Sheffield
Beech Hill Road
Tel: +44 (0)114 215 9519
Fax: +44 (0)114 271 1863
I am a clinician scientist with an interest in respiratory infection, immune deficiency and inflammation. I studied medicine in Cambridge and London, and undertook clinical training in London and Edinburgh. My PhD was supervised by Professor Chris Haslett and Professor Edwin Chilvers in Edinburgh, and identified a key role for the phosphoinositde 3-kinase (PI3K) signalling pathway in neutrophil priming and activation. I was awarded a Wellcome Trust Intermediate Fellowship to pursue this finding at the Inositide Laboratory at the Babraham Institute in Cambridge, with Dr Phill Hawkins and Dr Len Stephens. My subsequent appointment as a University Lecturer in Cambridge in 2007 enabled a more translational research focus, in particular studying the impact of hypoxia on neutrophil function and establishing novel imaging techniques using radiolabelled neutrophils and eosinophils in man; during this time I forged clinical and research links with the Department of Immunology in Cambridge. This collaboration facilitated the identification the ‘Activated PI3-kinase Delta Syndrome’ or APDS, a novel immune deficiency syndrome characterised by severe recurrent respiratory infection, viral infections, autoimmunity and lymphoproliferation, and caused by excessive PI3K delta signalling in immune cells. I was appointed as Professor of Respiratory Medicine at the University of Sheffield in 2015.
Defects in innate and adaptive immunity lead to infection with a predilection for the respiratory tract, yet immune cell infiltration underpins a range of inflammatory and allergic respiratory diseases such as chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS) and asthma. To clarify the role of dysregulated immunity in these diseases, I wish to address the following questions:
- How does immune cell function become deranged to promote disease pathogenesis rather than host defence?
- Can we identify cellular defects that predispose to recurrent respiratory infections?
- How can we use this knowledge to further diagnostic, prognostic and therapeutic interventions in diseases driven by aberrant immunity?
My current research funding encompasses the role of inappropriate neutrophil activation in COPD and ARDS, the impact of hypoxia on neutrophil function, and the role of PI3K delta in immune cell and airway biology.
I am committed to medical education and prior to my recent move to Sheffield was the Departmental lead for Educational Supervision. My teaching focuses on respiratory infection and host-pathogen interactions.
- Scientific Advisory Board member for the Institute of Ageing and Inflammation, University of Birmingham.
- MRC Clinical Research Training Fellowship panel member.
- External Examiner for Year 3 Medical Examinations, University of Edinburgh (2015-present).
- British Thoracic Society Scientific Committee member (2015–2018).
- British Thoracic Society Lung Infection Specialist Advisory Group member (2015-2018).
- British Lung Foundation Scientific Committee Member (2011-2017).
- Lead for Educational Supervision, Respiratory Medicine, Addenbrookes Hospital (2010-2015).
- Program Committee Member, American Thoracic Society, Respiratory Cell and Molecular Biology Assembly (2007-2011).
- Planning Committee Member, American Thoracic Society, Respiratory Cell and Molecular Biology Assembly (2009-2012).
- How does hypoxia impact on host-pathogen interactions?
- Contribution of hypoxic upregulation of neutrophil degranulation to airway disease and endothelial dysfunction in COPD
- Characterisation of a mouse model of the APDS (MRC program grant; with Dr Klaus Okkenhaug, Babraham Institute, Cambridge).
- Development of zebrafish models to characterise PI3K signalling in host-pathogen interactions (with Professor Steve Renshaw).
- Use of novel PI3Kδ inhibitors in APDS (MRC-Industrial Collaboration Award, GSK).).
- Identification of mutations in patients with bronchiectasis and/or recurrent infection (CTTV award with Dr David Michalovitch (GSK), Dr Paul Kelham (Wellcome Trust Sanger Centre) and Professor Andres Floto (Papworth Hospital NHS Foundation Trust)).
- Role of PI3K signalling in airway epithelial-mediated host defence.
- Role of hypoxia in driving antimicrobial evolution (with Professor Michael Brockhurst).
For key publications see below. For a full list of publications click here.
- PI3Kδ hyper‐activation promotes development of B cells that exacerbate Streptococcus pneumoniae infection in an antibody‐independent manner. Nature Communications, 9. View this article in WRRO
- British Lung Foundation/United Kingdom Primary Immunodeficiency Network Consensus Statement on the Definition, Diagnosis, and Management of Granulomatous-Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency Disorders. The Journal of Allergy and Clinical Immunology: In Practice, 5(4), 938-945. View this article in WRRO
- Clinical spectrum and features of activated phosphoinositide 3-kinase δ syndrome: A large patient cohort study.. J Allergy Clin Immunol, 139(2), 597-606.e4. View this article in WRRO
- Acute Respiratory Distress Syndrome Neutrophils Have a Distinct Phenotype and Are Resistant to Phosphoinositide 3-Kinase Inhibition. American Journal of Respiratory and Critical Care Medicine, 194(8), 961-973. View this article in WRRO
- Hypoxia upregulates neutrophil degranulation and potential for tissue injury. Thorax, 71(11), 1030-1038. View this article in WRRO
- PI3Kδ and primary immunodeficiencies. Nature Reviews Immunology. View this article in WRRO
- Phosphoinositide 3-Kinase Gene Mutation Predisposes to Respiratory Infection and Airway Damage. Science, 342(6160), 866-871.
- Use of Technetium-99m–labeled Eosinophils to Detect Active Eosinophilic Inflammation in Humans. American Journal of Respiratory and Critical Care Medicine, 188(7), 880-882.
- The Neutrophil in Chronic Obstructive Pulmonary Disease. Too Little, Too Late or Too Much, Too Soon?. American Journal of Respiratory Cell and Molecular Biology, 48(5), 531-539.
- Hypoxia Selectively Inhibits Respiratory Burst Activity and Killing of Staphylococcus aureus in Human Neutrophils. The Journal of Immunology, 186(1), 453-463.
- Gβγs and the Ras binding domain of p110γ are both important regulators of PI3Kγ signalling in neutrophils. Nature Cell Biology, 8(11), 1303-1309.
- RhoG Regulates the Neutrophil NADPH Oxidase. The Journal of Immunology, 176(9), 5314-5320.
- Sequential activation of class IB and class IA PI3K is important for the primed respiratory burst of human but not murine neutrophils. Blood, 106(4), 1432-1440.
- Moving in mysterious ways. Nature, 404(6774), 135-137.
- Functional Redundancy of Class I Phosphoinositide 3-Kinase (PI3K) Isoforms in Signaling Growth Factor-Mediated Human Neutrophil Survival. PLoS ONE, 7(9), e45933-e45933. View this article in WRRO