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Professor Derek Macallan

Professor of Infectious Diseases
Honorary Consultant Physician

Professor Derek Macallan is a Principal Investigator in the Infection and Immunity Research Institute, as well as a practising clinician in Infectious Diseases at St George's Hospital.

 

Derek Macallan trained in medicine at University College, Oxford and at the London Hospital Medical College before completing his postgraduate medical training in London and Oxford. He first came to St George’s in 1988 as a Registrar in Medicine and at that stage had a keen interest in Infectious Diseases, specifically in the way in which the body responds to and defends itself against infections. He joined George Griffin’s group to study the metabolic effects of HIV (AIDS wasting syndrome as it was then known) and tuberculosis and this formed the basis for his PhD, awarded in 1994.

During his research in metabolism he learned to use and apply stable (non-radioactive) isotope tracers in human studies. These are amazingly potent tools for investigating physiological and biochemical processes in vivo in clinical human studies. He then undertook a Medical Research Council (MRC) travelling fellowship to the University of California, Berkeley, where he developed a novel isotopic method for measuring rates of cell proliferation in vivo which could be applied in clinical studies. The context of these studies, in the late 1990’s) was an urgent need to understand the reason CD4 cells are lost in HIV infection.

Returning to the UK, Professor Macallan took up an MRC clinician scientist fellowship at St George’s, then a Senior Lectureship and was appointed Professor in 2007. He has continued to focus his research activities on in vivo lymphocyte kinetics and principally applied this approach to develop novel kinetic models of immune memory and HIV pathogenesis.

Clinical work has always been important to Derek. He was appointed an Honorary Consultant at St George’s Hospital in 1998. About half of his time is spent in clinical work – he looks after inpatients with infectious diseases on our specialist unit (McEntee Ward) and conducts a weekly HIV outpatient clinic in the Courtyard Clinic on the St George’s site.

More recently (2019) he was appointed a Non-Executive Director at Epsom and St Helier University Hospitals NHS Trust. He is a member of the British HIV Association Education and Scientific Subcommittee.

Personal Awards

2018:     Winston Churchill Memorial Trust Travelling Fellowship to Peter Doherty Institute, Melbourne, Australia.

2008:     Fulbright Commission, Distinguished Scholar Award to National Institutes for Health, Bethesda, MD. USA.

2005:    "Community Hero Award" nomination: UK coalition of People living with HIV/AIDS

1997:     Sir David Cuthbertson Medal: Nutrition Society, for research in Nutrition and Metabolism

1996:     MRC Travelling Fellowship to University of California, Berkeley. USA

1992:     Nutritional Research Foundation Travelling Fellowship: “Metabolic effects of TB in India”; Bangalore, India.

1977:     War Memorial Open Scholarship, University College, Oxford.

We know that white cells are critical for ensuring that we can fight infections, but how does the human body maintain the right number and the right types of white cell at all times? How do we still achieve this balance even in the face of challenges such as infections and ageing? How do we retain “memories” of past infections so as to defend ourselves better the next time we encounter them?

These are the type of broad questions that the Macallan research group is trying to answer. The specific focus of Derek’s research group is the investigation of human lymphocyte dynamics using in vivo stable isotope labelling. We use deuterium-labelled glucose and heavy water (deuterium oxide) to measure the turnover rates of cell populations in human clinical studies. We give these tracers orally to volunteers and then sample blood to obtain specific cell subpopulations of interest (isolated by flow cytometry or antibody-coated magnetic bead adhesion). We then extract cellular DNA and analyse nucleotide derivatives for deuterium content by gas-chromatography mass-spectrometry (GC-MS). Deuterium compounds are ideal for such studies because of their lack of toxicity (being non-radioactive and naturally-occurring) and ease of detection, even at very low abundances. Adding mathematical modelling (in collaboration with Becca Asquith at Imperial College, London) allows us to estimate cell division ad death rates and create models of how immune cells develop and are maintained.

Our main applications include, developing our understanding of how memory populations are maintained, the kinetic mechanisms underlying CD4 loss in HIV infection, immune changes in ageing, the dynamics of leukaemia cells in CLL and the effect of Lymphoedema on lymphocyte development. Recently completed and ongoing studies include:

  • An investigation of how different strains of HIV (CCR5-tropic versus CXCR4-tropic) affect the turnover rates of different lymphocyte subpopulations.
  • A study of why HIV-2 infection usually causes less pathology than HIV-1 infection. This study was conducted at the MRC Laboratories in The Gambia.
  • Investigations of how ageing affects the immune system, specifically whether “old” immune cells, defined according to CD28 and CD57 expression, continue to divide or enter a natural death cycle (apoptosis).
  • A study of how long leukaemic cells survive in chronic lymphocytic leukaemia (CLL) and whether agents to treat CLL affect the lifespan of such cells.
  • Exploration of the contribution of KIR (Killer cell immunoglobulin-like receptors) to T-cell memory.
  • Studies of the impact of lymphoedema on T-cell survival.
  • Elucidation of the relationship between classical, intermediate and non-classical monocytes in health and in sepsis.

 

Derek has received funding from MRC, Wellcome Trust, Jefferiss Trust, and Bloodwise (formerly Leukaemia Lymphoma Research).

Collaborations have been pivotal to Derek’s research programme. Collaborating with Peter Beverley at the Edward Jenner Institute for Vaccine Research was key to establishing his research portfolio His principal collaboration currently is with Becca Asquith at Imperial College. Other key collaborations include Cardiff University (David Price, Kristin Ladell), UCL (Arne Akbar, Simon Yona), King’s College London (Stephen Devereux), University of Roehampton (Robert Busch) and Institut Gustave Roussy in Paris (Eric Solary). Internally at SGUL, Derek has an exciting collaborative project with Pia Ostergaard and Peter Mortimer looking at lymphocyte dynamics in lymphoedema.

Derek has a keen interest in teaching. He regularly teaches undergraduate and postgraduates "at the bedside" on the infectious diseases unit and in clinic. His development of "Clinical PBL" as a teaching tool was published in Medical Education: A model of clinical problem-based learning for clinical attachments in medicine. Med Educ. 2009 Aug;43(8):799-807

https://www.ncbi.nlm.nih.gov/pubmed/19659494

He also teaches project students and PhD students within SGUL – a role he very much enjoys.

 

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