Professor Derek Macallan is a principal investigator in the Infection and Immunity Research Institute, as well as a practising clinician in infectious diseases.
He is also the clinical lead for the Clinical Infection Unit at St George’s University Hospitals NHS Foundation Trust and sees patients with complex infection problems, especially those related to tuberculosis and HIV. His research investigates the kinetics of immune cells within the body. The broad goal is to understand how the right number and right type of immune cells are maintained in the right place at the right time. This is the basis of the concept of “immune homeostasis”. We also want to know why and how things go wrong in situations such as ageing, HIV infection, and leukaemia.
The focus of Derek Macallan’s research group is the investigation of human lymphocyte dynamics using in vivo stable isotope labelling, a method developed by Derek Macallan during a research attachment at University of Berkeley, California. The group’s use deuterium-labelled glucose and heavy water (deuterium oxide) labelling to measure the turnover rates of T-cell populations. This is achieved by oral dosing of volunteers, followed by isolation of cell subtypes (identified by FACS or antibody-coated magnetic bead adhesion), DNA extraction and analysis of nucleotide derivatives for deuterium content by gas-chromatography mass-spectrometry (GCMS). Deuterium compounds are ideal for such studies because of their lack of toxicity (being non-radioactive and naturally-occurring). Analysis is performed at a dedicated in-house GCMS facility. Mathematical modelling approaches have been developed with collaboration with Becca Asquith’s group at Imperial College, London.
This approach has many potential applications and can be adapted to measure turnover rates of cells in solid tumours as well as circulating cells , and to RNA as well as DNA. Professor Macallan’s group’s main application is to develop our understanding of how memory populations are maintained and the kinetic mechanisms of immunopathology in HIV infection, ageing and leukaemia.
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 subpopulations4.
An investigation of why HIV-2 infection usually causes less pathology than HIV-1 infection. This study was conducted at the MRC Laboratories in The Gambia.(Revised manuscript under submission to Journal of Infectious Diseases)
An investigation of how memory populations are structured and whether this can be investigated by contrasting heavy water with heavy glucose labelling approaches, in collaboration with Imperial College, London and Professor David Price at Cardiff University.
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, in collaboration with Professor Devereux at King’s College, London.
The group’s future goals include development of models for immune ageing, application to investigate cells of the innate immune system and investigation of inter-relationships between innate markers such as KIR-genotype and memory cell lifespan.
Professor Macallan trained in medicine at University College, Oxford and the London Hospital Medical College and completed postgraduate medical training in London and Oxford. He completed his PhD on the metabolic effects of chronic infection in 1994. This focussed on human immunodeficiency virus (HIV) and tuberculosis (TB) as catabolic states, using stable isotopes tracers as tools to investigate in vivo kinetic processes.
During a Medical Research Council (MRC) travelling fellowship to the University of California, Berkeley, Professor Macallan applied these tracer technologies to the study of human cell turnover and developed a novel isotopic method for measuring rates of cell proliferation in vivo which could be applied in clinical studies.
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.
Since 2011, he has been clinical lead for the Clinical Infection Unit at St George’s Hospital and sees patients with complex infection problems, especially those related to TB and HIV.
Honours and awards
2009: Fulbright Commission, Distinguished Scholar Award.
2005: Nomination: "Community Hero Award": UK coalition of People living with HIV/AIDS.
1997: Sir David Cuthbertson Medal: Nutrition Society, for research in Nutrition and Metabolism.
1996: Travelling Fellowship to University of California, Berkeley: MRC.
1992: Nutritional Research Foundation Travelling Fellowship: Metabolic effects of TB in India.
Wake RM, Poulikakos P, Groth J, Harrison TS, Macallan DC. Evaluation of a pro-active strategy for managing tuberculosis-HIV co-infection in a UK tertiary care setting. Int J STD AIDS. 2013 May 1. [Epub ahead of print] PubMed PMID: 23635810.
Nyamweya S, Hegedus A, Jaye A, Rowland-Jones S, Flanagan KL, Macallan DC. Comparing HIV-1 and HIV-2 infection: Lessons for viral immunopathogenesis. Rev Med Virol. 2013 Feb 26. doi: 10.1002/rmv.1739. [Epub ahead of print] PubMed PMID: 23444290.
Vukmanovic-Stejic M, Zhang Y, Akbar AN, Macallan DC. Measurement of proliferation and disappearance of regulatory T cells in human studies using deuterium-labeled glucose. Methods Mol Biol. 2011;707:243-61. doi: 10.1007/978-1-61737-979-6_16. PubMed PMID: 21287340.
Zhang Y, de Lara C, Worth A, Hegedus A, Laamanen K, Beverley P, Macallan D. Accelerated In Vivo Proliferation of Memory Phenotype CD4(+) T-cells in Human HIV-1 Infection Irrespective of Viral Chemokine Co-receptor Tropism. PLoS Pathog. 2013 Apr;9(4):e1003310. doi: 10.1371/journal.ppat.1003310. Epub 2013 Apr 18. PubMed PMID: 23637601; PubMed Central PMCID: PMC3630096.
Wallace DL, Masters JE, De Lara CM, Henson SM, Worth A, Zhang Y, Kumar SR, Beverley PC, Akbar AN, Macallan DC. Human cytomegalovirus-specific CD8(+) T-cell expansions contain long-lived cells that retain functional capacity in both young and elderly subjects. Immunology. 2011 Jan;132(1):27-38. doi:10.1111/j.1365-2567.2010.03334.x. Epub 2010 Aug 25. PubMed PMID: 20738423; PubMed
Central PMCID: PMC3015072.
Macallan DC, Asquith B, Zhang Y, de Lara C, Ghattas H, Defoiche J, Beverley PC. Measurement of proliferation and disappearance of rapid turnover cell populations in human studies using deuterium-labeled glucose. Nature Protocols.2009;4(9):1313-27. doi: 10.1038/nprot.2009.117. Epub 2009 Aug 20. PubMed PMID: 19696750.
Professor Derek Macallan’s research group currently consists of Yan Zhang, Senior Research Assistant, and Raya Ahmed, PhD student.
He also co-supervises a Phd student at the National Institutes for Health, Bethesda, USA. His joint PhD student with Royal Holloway, University of London, Andrea Hegedus, completed her PhD in 2013.
Prof David Price, Dr Kristin Ladell (Cardiff University)
Becca Asquith, Prof Charles Bangham (Imperial College, London)
Prof Vincent Jansen (Royal Holloway, University of London)
Prof Steve Devereux (King’s College, London)
Dr Robert Busch (University of Cambridge)
Prof Peter Beverley (Jenner Institute, University of Oxford)
Prof Arne Akbar (University College, London)
Rick Koup, Costas Petrovas (Vaccine Research Centre, NIH, Bethesda, USA)
Professor Macallan’s group are supported by:
Leukaemia & Lymphoma Research
Medical Research Council
Professor Macallan is actively involved in teaching clinical undergraduate medical students, as well as being a teacher and educational supervisor for Infectious Diseases trainees on the SW London training programme.