Experimental

Before clinical trials are undertaken for a potential drug, vaccine, medical device, or diagnostic assay, the product is tested extensively in pre-clinical studies.  Such studies are lab-based, sometimes known as experimental research, and involve in vitro (test tube or cell culture) and in vivo (animals).

Our pre-clinical research is aimed at understanding disease pathways at the cellular, molecular, genetic, biochemical, physiological and pathological levels focused on identifying novel biomarkers to guide precision medicine and novel targets for drug development.

Interstitial lung disease

  • Investigation of matrix regulation in chronic lung disease:
    • Chronic respiratory disease is characterised by lung scarring or fibrosis. This work investigates the development of scar tissue in disease as diverse as pulmonary fibrosis, asthma and tuberculosis. By understanding the mechanisms that underlie the scarring process, we can help to develop drugs to overcome it.
  • Autoantibodies and pulmonary fibrosis:
    • Studying the role of auto-antibodies (antibodies that the body makes against its own organs) in pulmonary fibrosis. In particular, we are developing ways to looking for auto-antibodies that attack patients’ own blood vessels in patients with interstitial lung diseases including IPF and rheumatoid arthritis associated ILD.
  • Circulating white blood cells:
    • We have shown that a specific type of circulating white blood cells, called neutrophils, are different in patients with IPF and can help us predict which patients will do less well than others. We are trying to find out more about why this happens and whether the abnormal neutrophils are the result of, or the cause of, the lung disease.
  • Activation of white blood cells in the lung:
    • We have shown that white blood cells are activated in the lungs of patients with pulmonary fibrosis and are carrying out studies to find out what causes this activation and whether it can be reversed. In particular, we are investigating the effect of low oxygen concentration on white cell activation in IPF and other diseases.
  • Airway epithelial project:
    • We are able to look at the interactions of white cells and the lung epithelium and compare the white cells from patients with pulmonary fibrosis to those from control patients with no lung disease. We are particularly interested in how the mucin Muc5B (that gives sputum it’s ‘stringy’ quality) might influence these interactions. We are also looking at whether genetic material from the lung can be detected in blood of patients with IPF allowing a test for earlier diagnosis, and to measure response to novel treatments.
  • Platelets and pulmonary fibrosis:
    • Investigating the role of platelets in IPF and other ILDs. We have studies looking at whether platelets accumulate in the lungs of patients with lung fibrosis, and whether platelets are abnormally ‘sticky’ in these patients.
  • An investigation into the mechanisms of lung injury and repair in inflammatory, infective, fibrotic and destructive lung disease:
    • We aim to understand more about how the lung is able to recover from damage caused by infection, inhaled toxins (including pollution), inflammation and other diseases.
  • The coagulation cascade in Idiopathic Pulmonary Fibrosis – the manipulation of the coagulation cascade using dabigatran and assessing the contribution of this biological pathway in IPF by performing PET scans pre- and post- treatment:
    • For many years, it has been recognised that patients with IPF are at increased risk of blood clots. We are looking at whether patients derive benefits from taking drugs that ‘thin’ the blood to prevent clots. A special scanner called a PET CT (positron emission topography, computerised topography) is able to give more information about the lungs of patients with scarring. This scanning technique will be used to see if blocking coagulation helps treat the disease.We are completing a study this year and hope to publish the results and apply for a bigger study.

Lung infections

  • Pneumonia:
    • Professor Brown leads an internationally recognised research group into the pneumococcus aiming to identify why it can cause pneumonia, and to develop new vaccines or other treatments to prevent pneumonia. The research is mainly laboratory-based. His group has published multiple research papers on pneumonia or the pneumococcus, including recent papers describing new methods of trying to prevent infections using novel vaccine approaches.
  • Tuberculosis:
    • It is important to grow colonies of TB bacteria in the laboratory using special culture techniques from the specimens we ask patients to provide, this confirms the diagnosis and also tells us which antibiotics the bacteria are sensitive to. Growing TB bacteria can take up to 6 weeks and samples from glandular TB are more difficult to culture – over half of these samples never grow and therefore treatment proceeds on the basis of clinical probability. As a result, we need better methods of confirming a diagnosis of TB, and this is an active area of research at University College London.

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