Professor Joseph Keane

  Apoptosis   Host, Pathogen interactions   Infectious diseases   Innate immunology   Lung Cancer   Medicine   Respiratory System

THE HOST RESPONSE TO TUBERCULOSIS

Macrophage Responses We asses the macrophage response to infection using in vitro and ex vivo models of human alveolar macrophages infected with Mycobacterium tuberculosis. We have used these experiments to define the role of macrophage cytokine production, bacterial killing, phagolysosome maturation, and cell death in the immune response to tuberculosis. By using human alveolar macrophages from subjects undergoing bronchoscopy we have been able to define clinically relevant innate immune responses to this important organism.

Cell Mediated Immunity Using human and murine models of disease we have been able to characterise both the pro and anti inflammatory immune response to Mycobacterium tuberculosis. Specifically we have demonstrated new mechanism whereby human alveolar macrophages generate a tolerogenic response to Mtb infection; which is reflected in T-cell changes that can potentially accommodate the invading pathogen.

The study of tuberculosis susceptible human hosts In our translational work; we have characterised the immune response of patients taking TNF-Blockers, cigarette smokers, and patient deficient in vitamin D. In this regard we have helped define their unique host susceptibility to disease with Mycobacterium tuberculosis.

Dublin TB group Our lab is an integral part of the Trinity College Immunology Research centre, including investigators who do TB research such as L O'Neill, K. Mills, P. Fallon, E. Lavelle and C. O'Farrelly. We co-supervise work on new inhalable TB therapies for TB with Dr. Sally Ann Cryan (RCSI). These PI's and a critical mass of TB investigators across Dublin are available to collaborate on future grant calls, and include Prof. Stephen Gordon, mycobateriologist, UCD.

Clinical Tuberculosis Research With on-site access to the largest TB cohort in Ireland, we have been in a position to define the role of new diagnostic and therapeutic options for TB. We have reported on the use of EBUS-TBNA in the diagnosis of isolated mediastinal tuberculous lymphadenopathy. We have also defined the public health hazard of prolonged infectiousness seen in our patients who smoke cigarettes after commencement of anti-TB treatment.

New TB Diagnostics The role of IGRA in the diagnosis of Latent TB infection: We are undertaking bench experiments to improve the signal to noise ratio and potentially shorten the blood incubation period in IGRA tests. In our clinics, we are testing IGRA performance in selected populations that are uniquely susceptible to progression from LTBI to tuberculosis disease.

TB research is funded by SFI, HRB and the RCDH Trust

Lung Cancer

• The genetic basis of lung cancer: At St. James's we see 25% of the Irish lung cancer patients. My lab is collaborating with Boston University who are looking at the genetic profile of cells from these patients to address the questions 'Why do some smoker get lung cancer, and some smokers do not'. It is hope that this transcriptomics approach will allow for early detection for this disease that is almost always lethal because it presents late.
• The accurate staging of lung cancer using whole body MRI or PET