2017 (Jan) Lecturer in Immunology and Ageing, School of Biosciences and Medicine, University of Surrey, Guildford, UK
2010-2017 Senior Postdoctoral Research Associate, Division of Infection and Immunity, UCL, UK
2006-2010 PhD Candidate, School of Sport and Exercise Sciences, University of Birmingham, UK
My research is focused on understanding endocrine regulation of the immune system and how the immune system changes with age, with a particular focus on T cell immunology. Senescence of the immune system is believed to contribute to immune function decline with age, resulting in increased illness and infection in older individuals. As the proportion of over 65 year olds in the UK is expected to increase to >25% of the population by 2030, there is an urgent need to understand how the immune system changes with ageing, why these changes occur and, importantly, how we may intervene to reverse of prevent loss of immune function in the elderly.
Every-day physiological and psychological stressors can greatly affect T cell immunity, and therefore our health in general. The two main mediators of this stress response are the hormones adrenaline and cortisol, which are both important regulators of T cell immunity and the immune system in general. These hormones modulate almost every aspect of T cell immunity, including the anatomical distribution of cells, and cell functions such as, cytokine production. Disruptions of normal circadian rhythmicity of adrenaline and cortisol secretion, as is seen in shift workers and during psychological stress, can thus have profound effects on T cell immunity and this is particularly true in elderly individuals. Furthermore, prolonged stress has been found to cause premature and accelerated ageing of the immune system.
Using a combination of human in-vivo and in-vitro systems my research aims to identifying the immune alterations brought about by endocrine control of T cell immunity and the cellular mechanism involved. The overarching aim is to find novel interventions to manipulate endocrine regulation of T cells and promote desirable immune outcomes.
• Dr Sian Henson, Centre for Microvascular Research, Queen Marys, University of London, UK. T cell metabolism and immunosenescence.
• Prof Arne Akbar, Infection and Immunity, UCL, UK. T cell immunosenescence, cell signalling and human skin challenge model.
• Dr Anis Larbi, Singapore Immunology Network (SIgN), A*STAR Institute, Singapore. Telomere analysis, deep immunophenotyping, gene expression arrays and proteomics characterisation of immunosenescence.
• Prof Gary Frost and Dr Ed Chambers, Department of Investigative Medicine, Imperial College London, UK. Effects of nutrition, the microbiome and shift work on immune function.
• Prof Daniel Gomes, Universidade Federal do Espírito Santo, Brazil. Impact of immune ageing and neuroendocrine factors on Leishmania immunology.
• Dr Jos Bosch, Department of Clinical Psychology, University of Amsterdam. Netherlands. Experimental and epidemiological studies of psychoneuroimmunology.
Academic lead for FACS facility
BMS2045: Introduction to Immunology
MMIM023: Medical Microbiology
MMVM001: Veterinary Microbiology
Postgraduate research supervision
Supervision of BSc, MSc and PhD research projects
Current Group Members:
Phillip Morgan (PhD Student)
The results show that Sal reduced the percentage of IFN-³+ CD4 and IFN-³+ CD8 T cells both when applied directly to isolated T cells, and indirectly via treatment of APC. These inhibitory effects were mediated via a ß2 adrenergic-dependent pathway and were stronger for CD8 as compared to CD4 T cells. Similarly, the results show that Sal suppressed cytotoxicity of both CD8 T and NK cells in vitro following stimulation with Chinese hamster ovary cell line transfected with MICA*009 (T-CHO) and the human erythromyeloblastoid leukemic (K562) cell line. The inhibitory effect on cytotoxicity following stimulation with T-CHO was stronger in NK cells compared with CD8 T cells.
Thus, targeting the ß2AR on lymphocytes and on APC leads to inhibition of inflammatory cytokine production and target cell killing. Moreover, there is a hierarchy of responses, with CD8 T cells and NK cells inhibited more effectively than CD4 T cells.
in-`ain L, Dechanet-Merville J, Derhovanessian E, Ferrando-Martinez S, Franceschi C, Frasca D, Fulöp T, Furman D, Gkrania-Klotsas E, Goodrum F, Grubeck-Loebenstein B, Hurme M, Kern F, Lilleri D, López-Botet M, Maier AB, Marandu T, Marchant A, Matheï C, Moss P, Muntasell A, Remmerswaal EBM, Riddell N, Rothe K, Sauce D, Shin E-C, Simanek AM, Smithey MJ, Söderberg-Nauclér C, Solana R, Thomas PG, van Lier R, Pawelec G, Nikolich-Zugich J (2014) New advances in CMV and immunosenescence, Experimental Gerontology 55 pp. 54-62 Elsevier
Stimuli that activate the sympathetic nervous system, such as acute psychological stress, rapidly invoke a robust mobilization of lymphocytes into the circulation. Experimental animal studies suggest that bone marrow-derived progenitor cells (PCs) also mobilize in response to sympathetic stimulation. Here we tested the effects of acute psychological stress and brief pharmacological ²-adrenergic (²AR) stimulation on peripheral PC numbers in humans.
In two studies, we investigated PC mobilization in response to an acute speech task (n = 26) and ²AR-agonist (isoproterenol) infusion (n = 20). A subset of 8 participants also underwent the infusion protocol with concomitant administration of the ²AR-antagonist propranolol. Flow cytometry was used to enumerate lymphocyte subsets, total progenitor cells, total haematopoietic stem cells (HSC), early HSC (multi-lineage potential), late HSC (lineage committed), and endothelial PCs (EPCs).
Both psychological stress and ²AR-agonist infusion caused the expected mobilization of total monocytes and lymphocytes and CD8+ T lymphocytes. Psychological stress also induced a modest, but significant, increase in total PCs, HSCs, and EPC numbers in peripheral blood. However, infusion of a ²AR-agonist did not result in a significant change in circulating PCs.
PCs are rapidly mobilized by psychological stress via mechanisms independent of ²AR-stimulation, although the findings do not exclude ²AR-stimulation as a possible cofactor. Considering the clinical and physiological relevance, further research into the mechanisms involved in stress-induced PC mobilization seems warranted.
t Cell Receptor Repertoire of Naïve
and Memory subsets Using an
Integrated experimental and
Computational Pipeline Which Is
Robust, economical, and Versatile, Frontiers in Immunology 8 1267 Frontiers Media
and non-infectious diseases. We describe a protocol for amplifying, sequencing, and
analyzing TCRs which is robust, sensitive, and versatile. The key experimental step is
ligation of a single-stranded oligonucleotide to the 32 end of the TCR cDNA. This allows
amplification of all possible rearrangements using a single set of primers per locus. It
also introduces a unique molecular identifier to label each starting cDNA molecule. This
molecular identifier is used to correct for sequence errors and for effects of differential
PCR amplification efficiency, thus producing more accurate measures of the true TCR
frequency within the sample. This integrated experimental and computational pipeline
is applied to the analysis of human memory and naive subpopulations, and results in
consistent measures of diversity and inequality. After error correction, the distribution of
TCR sequence abundance in all subpopulations followed a power law over a wide range
of values. The power law exponent differed between naïve and memory populations, but
was consistent between individuals. The integrated experimental and analysis pipeline
we describe is appropriate to studies of T cell responses in a broad range of physiological
and pathological contexts.
gut microbiota, has been shown to alter hepatic metabolic processes that reduce lipid storage. We
aimed to investigate the impact of raising colonic propionate production on hepatic steatosis in
adults with non-alcoholic fatty liver disease (NAFLD). Eighteen adults were randomised to receive
20g/day of an inulin-propionate ester (IPE), designed to deliver propionate to the colon, or an
inulin-control for 42-days in a parallel design. The change in intrahepatocellular lipid (IHCL)
following the supplementation period was not different between groups (P=0.082), however IHCL
significantly increased within the inulin-control group (20.9±2.9 to 26.8±3.9%; P=0.012; n=9), which
was not observed within the IPE group (22.6±6.9 to 23.5±6.8%; P=0.635; n=9). The predominant
SCFA from colonic fermentation of inulin is acetate, which in a background of NAFLD and a
hepatic metabolic profile that promotes fat accretion, may provide surplus lipogenic substrate to the
liver. The increased colonic delivery of propionate from IPE appears to attenuate this acetatemediated
increase in IHCL.