PI3K signalling in COPD
Research type
Research Study
Full title
PI3K SIGNALING AND ABERRANT NEUTROPHIL FUNCTION IN COPD; IMPLICATIONS FOR DISEASE SUSCEPTIBILITY, PROGNOSIS AND THERAPEUTIC TARGETING.
IRAS ID
162164
Contact name
Elizabeth Sapey
Contact email
Sponsor organisation
University of Bimingham
Duration of Study in the UK
3 years, 0 months, 4 days
Research summary
COPD is a pulmonary disease, associated with chronic morbidity and extensive health care utilisation. Treatment strategies are limited. New treatments are needed, but mechanisms of disease remain poorly understood. Neutrophils (PMN) are white cells that fight infection. They can cause tissue damage if they are abnormally activated. There is increasing evidence of abnormal PMN function in COPD, present across disease severities but not seen in other chronic inflammatory pulmonary conditions. Our data strongly suggest this is caused by aberrant Phosphoinositide 3 Kinase (PI3K) signaling. We hypothesise that abnormal neutrophil function contributes to COPD progression and is the result of aberrant signalling in the PI3K pathway.
We aim to identify the mechanism that causes abnormal PMN functions in COPD and determine if this is a susceptibility factor in disease development, both an important therapeutic target for drug development and a potential screening target for disease susceptibility.
Key questions to be addressed are:
1. Does defective PMN functioning predict the onset, progression or clinical phenotype of COPD?
2. Is the defect due to aberrant PI3K signaling?
3. What is the molecular basis of the defect?We will assess blood PMN function in COPD and healthy controls. We will assess if the defect persists during acute exacerbations (associated with heightened inflammation and poorer health) and in PMNs that have transmigrated to the lung.
We will assess if the defect is present in family members of patients with COPD. If so, this would suggest a genetic association for COPD and PMN behavior, supporting our belief that altered PMN function is inherent in the development of COPD. Identified mechanisms could then be used to screen at risk individuals. We will assess PI3K signaling in COPD and healthy smoker control PMNs to determine if altered protein signaling is directly associated with the defective cell behavior.
REC name
East Midlands - Nottingham 1 Research Ethics Committee
REC reference
14/EM/1230
Date of REC Opinion
12 Dec 2014
REC opinion
Further Information Favourable Opinion