Staff Profile

From bedside to bench and back again - our research is all about what children with inborn errors of immunity can teach us about the normal immune system, and how that knowledge can help us look after patients better. I am a clinical paediatric immunologist at the Great North Children's Hospital, which is home to a supra-regional service for children with primary immunodeficiencies. My work is aimed at understanding the cellular and molecular basis of inborn errors of immunity and how this informs our knowledge of the normal immune system.

The human immune system has evolved to protect us from a bewildering array of germs, a job it usually performs unnoticed. We can think of the immune system as a network of armed forces that cooperate to defend us. When one element of these defences is weakened, it can leave us critically exposed to certain threats. Unusual or severe infections in young children can indicate a problem with the genes that determine how our immune system works. If affected children survive, they may suffer ongoing ill-health owing to chronic infection, stunted growth and lung damage. Sometimes this is accompanied by other problems such as the "friendly fire" of autoimmune disease or blood cancers. This type of immunodeficiency tends to run in families and is commoner in children whose parents are related to each other.

At the Great North Children's Hospital (GNCH), we care for hundreds of patients with inherited immunodeficiency, but the faulty gene can't always be pinpointed. Making a genetic diagnosis is important for two main reasons, one medical and one scientific:

(1) An accurate diagnosis can help doctors and families make the right treatment decisions. Many immunodeficiencies can now be cured by replacing the immune system with a bone marrow transplant. Unfortunately, this is an unpleasant and risky procedure. Scientists continue to work on smarter methods to replace or repair just the faulty gene. Where cure is not possible we may be able to use targeted treatments to replace the missing function. We can also be better prepared to prevent and treat complications if we know what to expect.

(2) Linking the faulty gene to the resulting pattern of disease tells us about its normal function. By studying individuals with inherited immunodeficiency, we can learn a great deal about what is important for human immunity. This knowledge can also help us understand the ways germs get round our immune system to cause disease.

My research addresses both these priorities by searching for the underlying cause of unexplained immunodeficiencies. We characterise the faulty immune system in detail to better describe how it is misbehaving. We use modern DNA sequencing methods to look for genetic changes that may link with disease. We test the strength of that link within the family and the wider population.   We try to find out how the genetic change interferes with normal immune function by experiments in the test tube.

As soon as a linked genetic change is confirmed, this can be fed back to the clinical team and inform patient care. Families can then benefit from genetic counselling and the possibility of early diagnosis for other affected family members. We share our research findings with the medical community at large so that patients with a similar disease pattern can be screened for the same genetic problem. We believe our work will lead to improved scientific understanding of human immunity, which is fundamentally important to health and disease.

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Group members:

Lab manager: Angela Grainger

Postdocs: Karin Engelhardt, Jarmila Spegarova, Rui Chen, Helen Griffin, Sarah Withers

PhD students: Katie Hatton, Alex Nicols, Matt Drummond, Lulu Wang

Clinical trainees: Ina Schim van der Loeff, Su Han Lum, Rachel Anderson, Manisha Ahuja, Tom Altmann

PIs: Sophie Hambleton, Chris Duncan, Becky Payne, Kate Madden

Postgraduate Supervision

We welcome postgraduate students who are interested in translational immunology research.

Funding (SH)

MRC DPFS grant 2022-2026

Wellcome Investigator Award 2018-2023

Sir Jules Thorn Charitable Trust Biomedical award 2013-2018

MRC clinician scientist award 2008-2012

Undergraduate Teaching

Extensive experience of mentoring, teaching and assessing students of medicine and biomedical sciences.

Postgraduate Teaching

I play an active role in postgraduate education within my clinical subspecialty including delivery of registrar training and running study days. I teach Immunobiology to MRes students and supervise research projects at all levels.  I participate in various clinical postgraduate courses including the ESID summer school, Advanced Immunology Winter School and the Oxford Paediatric Infectious Diseases Diploma.