Dr Matt O'Shea MBChB, MRCP, FRCPath, DPhil (Oxon), DTM&H

• Certificate of Completion of Training (CCT) in Infectious Diseases and Clinical Microbiology, 2019
• Fellow of the Royal College of Pathologists (FRCPath), 2019
• Doctor of Philosophy (DPhil), University of Oxford, 2016
• Diploma in Tropical Medicine and Hygiene (DTM&H) (Distinction), Liverpool School of Tropical Medicine & Hygiene, 2010
• Member of the Royal College of Physicians (MRCP), 2009
• Bachelor of Medicine and Bachelor of Surgery (MBChB), University of Birmingham, 2003
• Master of Philosophy (MPhil) in Infection, University of Birmingham & Naval Health Research Center San Diego, 2002
• Bachelor of Science (BSc) in Medical Biochemistry (First Class Hons), University of Birmingham, 1996

Dr O’Shea received his BSc in Biochemistry from the University of Birmingham in 1996 and then went on to study Medicine there (1997-2003). Interested in academic medicine and, in particular, infectious diseases and tropical medicine from an early stage, he undertook an MPhil by Research in Infection at NHRC in San Diego (2000-2001).

After qualifying in Medicine (MBChB, 2003) he undertook clinical rotations in Birmingham and Worcester. In 2009 he completed MRCP and subsequently started specialty clinical training in Infectious Diseases in the West Midlands Deanery (Heartlands Hospital). Dr O’Shea completed the DTM&H at the Liverpool School of Tropical Medicine and Hygiene (2010) and has undertaken clinical work in resource-poor settings (Malawi, Afghanistan and Sierra Leone).

Having been awarded a Wellcome Trust Research Training Fellowship and Senior Scholarship (Corpus Christi College, Oxford) he completed his DPhil at the Jenner Institute (University of Oxford) in 2016 on Tuberculosis (TB) immunology (The characterisation of mycobacterial control profiles and underlying immune signatures in patients with latent tuberculosis infection and active disease).

Dr O’Shea then returned to Birmingham to complete clinical training and to take up an Honorary Clinical Lectureship role in the IMI. During this time he established a research group with a portfolio of clinically-relevant, infection-related research, primarily focussed on TB and gastrointestinal helminths. Dr O’Shea was elected FRCPath in 2019 and dual accredited as a Consultant in Infectious Diseases and Clinical Microbiology thereafter.

In addition, Dr O’Shea is a military clinician (Royal Navy and Defence Medical Services) and has deployed extensively since commissioning in 1999. He is the Inaugural Lecturer in Defence Pathology and a member of the Academic Department of Military Medicine at the Royal Centre for Defence Medicine, Birmingham.

Dr O’Shea teaches on the MBChB, BMedSc and Postgraduate courses on various aspects of infection diseases and microbiology. He also delivers clinical bedside teaching to medical students and junior doctors on the wards.

• Intercalated BMedSc
• MBChB - years 3-5 ward-based clinical teaching

Dr O’Shea supervises Doctoral students in clinically-relevant, infection-related research, primarily focussed on the human host immune response to mycobacteria (M.tuberculosis), vaccine development and novel TB diagnostics and therapeutic approaches.

If you are interesting in studying any of these subject areas please contact Dr Matt O'Shea directly, or
for any general doctoral research enquiries, please email mds-gradschool@contacts.bham.ac.uk

For a full list of available Doctoral Research opportunities, please visit our Doctoral Research programme listings  

Current members

Dr Erin Aldera – Post-Doctoral Scientist

Erin pursued both her undergraduate and postgraduate studies at the University of Cape Town, graduating with a BSc specialising in Physiology and Microbiology in 2011, BSc (Med)(Hons) in 2012 and PhD in 2018. For her doctoral studies she investigated early-life immunity and the susceptibility of children to mycobacteria by relating vaccine- and helminth-specific antibody responses to their mycobacterial infection outcome. Erin joined the O’Shea group in early 2019 as a Newton International Fellow. Erin is examining the role that helminth-induced eosinophils play in the host immune response to mycobacterial infection by exploring whether these innate cells (classically linked to helminth infection control) can inhibit mycobacterial growth and the mechanisms used.

Charlotte Jones – Senior Laboratory Technician

Charlotte joined the O'Shea group in August 2016, after working for Professor Adam Cunningham on immune responses to Salmonella Typhimurium. Charlotte's background is in microbiology after graduating from the University of Birmingham in Cell and Molecular Biology (BMedSci, 2010). As she has always enjoyed studying, Charlotte undertook a Masters of Biomedical Science by flexible learning with Nottingham Trent University in 2015, graduating in 2017. Since her graduate degree, she has developed an interest in Mycobacterium tuberculosis, particularly the immunological relationship between latent infection and active disease. Charlotte was thrilled to take her current position to study this area using clinical samples and a variety of laboratory techniques (e.g. ELISAs, ELISpot/FluoroSpot, flow cytometry and BACTEC MGIT system).

Dr Danai Papakonstantinou – PhD Student

Danai graduated from the Medical School of the University of Athens (Greece) with an MD in 2005 and went on to complete a Master’s Degree and the Diploma in Tropical Medicine (DTM&H) at the London School of Hygiene and Tropical Medicine (2008-2009). Danai has worked as a medical doctor in Greece and the UK for more than 10 years and specialises in Infectious Diseases and General Internal Medicine in the West Midlands. Danai holds an honorary contract with Heartlands Hospital (Birmingham) as a Senior Registrar in Infectious Diseases and holds a specialty certificate in Infectious Diseases (British Infection Association and Royal College of Physicians). Danai is currently a PhD student in the O’Shea group (co-supervisors Professor Alan McNally and Professor Adam Cunningham) and holds a Global Challenges Scholarship (University of Birmingham). Danai is using bioinformatics to study the Mycobacterium tuberculosis genome to identify novel TB vaccine candidates and antigens for TB diagnostics.

Dr Gabby Morley – PhD Student

Gabby graduated from the University of Birmingham in 2015 with Honours in Medicine and Surgery (MBChB Hons). Through her work as a medical doctor, she developed a keen interest in infectious diseases, however seeing first-hand how certain infections were becoming more challenging to treat due to the rise of antimicrobial resistance. This interest led Gabby to apply for the Wellcome Trust Antimicrobial and Antimicrobial Resistance Doctoral Training Programme and start work in Dr Matt O’Shea’s group, at the University of Birmingham, investigating human immune responses to Mycobacterium tuberculosis (M.tb; co-supervisor Professor Adam Cunningham). Gabby's work aims to increase understanding of the human-M.tb interaction, with particular emphasis on the humoral response to M.tb, to facilitate novel management strategies for tackling drug-resistant M.tb.

Recent past members

Roxanne Pillay – Visiting Research Student

Roxanne is a registered Medical Technologist with the Health Professions Council of South Africa (HPCSA), specialising in Clinical Pathology and Chemical Pathology. She obtained a National Diploma (Biomedical Technology) and Bachelor of Technology (Biomedical Technology) from Durban University of Technology, South Africa, in 2006 and 2012 (respectively). She has since worked as a medical technologist in various pathology laboratories in South Africa. Roxanne has extensive experience in diagnostic testing in clinical pathology and also in implementation and maintenance of quality assurance systems for medical laboratories (ISO15189) and laboratory management. Her academic career began in 2017 when she joined the Mangosuthu University of Technology, South Africa as an NGAP lecturer. She was, until recently, a visiting research student at University of Birmingham (Dr Matt O’Shea’s lab) and is participating in an ongoing collaboration between South Africa and Birmingham as part of her Masters and PhD studies. Roxanne's research focuses on the direct interactions between helminths and bacteria with the aim of identifying novel antimicrobial agents.

Themes

Tuberculosis, helminths, B cells, antibodies, T cells, generation and maintenance of adaptive responses, vaccination, immune homeostasis, immune modulation.

Lay summary

Our work aims to understand how the human immune system responds to infection with Mycobacterium tuberculosis. We also study how other pathogens influence this immune response and whether they have an enhancing or diminishing effect. By increasing our knowledge of these processes, we can generate new vaccines and treatments to tackle the huge burden of TB.

Overview 

Mycobacterium tuberculosis (M.tb), the bacterial pathogen which causes tuberculosis (TB), is an ancient disease and the leading cause of death from a single infectious agent globally.  The World Health Organisation estimates that TB accounts for over 10 million new infections and 1.3 million deaths per year. The staggering scale of the TB disease burden is compounded by HIV co-infection and the emergence of multi-, extensively- and now totally-drug resistant strains of M.tb. Furthermore, modelling suggests that almost 25% of the world’s population has latent (dormant) infection, representing a huge reservoir of potential new disease and thus infectiousness.

However, infections rarely occur in isolation and there is significant overlap between M.tb and other endemic diseases in certain regions of the world. For example, one third of the world’s population is thought to be infected with soil-transmitted helminths and the helminth-M.tb co-infection rate is estimated at 20-35% in some low-middle income countries. This highlights that the geographical overlap of these pathogens is not inconsequential and frequently effects very vulnerable individuals. Our current knowledge about how helminths might influence M.tb infection is limited.

It is widely acknowledged that improved diagnostic tests, novel antibiotics and therapeutics are required to tackle the global TB epidemic. While stopping TB transmission with effective anti-tuberculous treatment is one of the cornerstones of TB control programmes, the discovery of a new globally effective TB vaccine remains the most cost effective, long-term control strategy.

Improved understanding of human-M.tb interactions, and the influence of co-infections, will provide opportunities to exploit the immune response to M.tb and therefore has potential translational clinical application through the development of novel diagnostics and therapeutics.

Our research uses clinical samples, in vivo and ex vivo models of infection and a variety of techniques to study immune responses to mycobacteria. While our particular focus is on adaptive immunity, we are also engaged in studying the contribution of innate responses in the control of M.tb.

Some examples of current research themes in the O’Shea laboratory include:

1. How B cell and antibody responses to mycobacterial antigens develop and assessing their role in the control and pathogenesis of M.tb infection.
2. Characterisation of antibody response profiles to proteinaceous and non-proteinaceous M.tb antigens in clinical samples from patients with different forms of TB infection and disease at baseline and in response to therapy.
3. Generating monoclonal antibodies directed against mycobacterial antigens to study their role in modulating responses to M.tb and their application in novel diagnostics and therapeutics.
4. Using computational biology and bioinformatics to identify sub-dominant M.tb antigens as a novel approach to find targets for candidate vaccine development.
5. Understanding the human host immune response across the spectrum of latent infection and TB disease and its relationship to mycobacterial control and pathogenesis.
6. How gastrointestinal helminth infections affect host homeostasis, immune function and the modulation of responses to mycobacteria.
7. Whether helminth-activated eosinophils have an anti-mycobacterial role in the control of M.tb infection.

Our work has shown that patients with active disease have the greatest control of mycobacterial growth in a whole blood mycobacterial growth inhibition assay, whilst there is a continuum of responses among latently infected patients, likely related to the degree of immune activation in response to bacillary load. The improved control we have observed is correlated with multiple factors including inflammatory monocytes, activated and atypical memory B cells, IgG1 responses to M.tb-specific antigens and serum cytokines/chemokines. Our findings are important as they offer a method to stratify subclinical TB infections and the future potential to identify individuals most at risk of progressing to active disease. In addition, we have identified a significant negative association between gastrointestinal hookworm and latent TB infections. Blood from individuals with hookworm have a greater ability to control virulent mycobacterial growth in vitro than from those without, which is lost following hookworm treatment. An eosinophil-associated differential gene expressioncharacterises the whole blood transcriptome of hookworm infection and correlates with improved mycobacterial control. These data suggest a possible anti-mycobacterial role for helminth-induced eosinophils which are investigating further.

Dr O’Shea’s other activities include:

• Reviewer for a number of internationally-competitive journals and funding agencies in the UK and abroad
• Member of the IMI Management Board
• Examiner for PhD and MD candidates in UK and overseas
• Member of the Military Infection Working Group

Professional memberships include:

• Royal College of Physicians
• Royal College of Pathologists
• Royal Society of Medicine
• British Infection Association
• British Society of Immunology
• Hospital Infection Society
• The Acid Fast Club