Professor Heather Wilson

Professor Heather Wilson
PhD

Chair in Immunology

Overview
Professor Heather Wilson
Professor Heather Wilson

Contact Details

Telephone
work +44 (0)1224 437350
Email
Address
The University of Aberdeen Room 3.24 School of Medicine, Medical Sciences & Nutrition, University of Aberdeen, Institute of Medical Sciences, Foresterhill Aberdeen Scotland AB25 2ZD

Biography

 

I graduated with a first class honours degree in Biochemistry  and was awarded a Carnegie prize scholarship to fund my PhD investigating lipid mediators driving coronary heart disease (awarded 1990). My early postdoctoral years focussed on factors mediating the pathophysiology of atherosclerosis and progression of glomerulonephritis to end stage renal disease. I was awarded MRC, Kidney Research UK and British Heart Foundation funding to continue my postdoctoral studies at Aberdeen University on the effects of macrophage inflammatory mediators on controlling glomerular extracellular matrix turnover and how increased deposition and/or decreased protease degradation resulted in renal scarring. A further MRC funded project focussed my research interests to the earlier inflammatory stage of nephritis and the cellular and molecular mechanisms controlling glomerular inflammation, focussing on the role of macrophages in experimental models. My current research is primarily directed towards understanding the signalling pathways that control macrophage activation, especially in nephritis, atherosclerosis and wound healing. I also have interests in macrophage signalling pathways relating to infection control. I am an active member of the Renal Association, British Society of Immunology and Biochemical Society. I teach on and coordinate BSc, MSc and MBChB courses.

 

Research

Research Interests

 

My research interests are directed towards a better understanding of the role of macrophages and other immune cells in controlling the pathogenesis of inflammatory and immune-mediated diseases. I have focussed primarily on the factors that polarise macrophages to pro- or anti-inflammatory subsets and the ways in which differentially activated macrophage subsets regulate tissue injury or tissue repair, especially in rodent models of nephritis and human atherosclerosis and wound healing. The aim is to be able to control immune and inflammatory mediated diseases by manipulating macrophage function. For this I am dissecting the role of the intracellular signalling pathways that direct macrophage activation, and how these pathways can be switched to exploit macrophage reparative attributes and restore regulation to the inflammatory response. I have developed a multitude of techniques to efficiently isolate tissue infiltrating macrophages and analyse their intracellular signalling pathways and using these have, for example, demonstrated that inhibiting the SOCS3 and PTP1B induces macrophages to become profoundly anti-inflammatory when exposed an inflamed environment.  

 

Current Research

 

My research is currently focussed on manipulating macrophage function using more physiological inhibitors of cytokine signalling and using siRNA knockdown technology and adenoviral based gene over-expression systems have identified how suppressor of cytokine signalling (SOCS)1 and SOCS3 proteins can deviate macrophage function in vitro (Liu et al Journal of Immunology, 2008, Whyte et al J Leuk Biol). I am also determining effects of nrf2 inducers to alter macrophage properties and foam cell formation. Ultimately, I aim to translate our findings and use "switching" of the function of physiological macrophages via small molecule drugs, for treatment of inflammatory diseases. I am also exploring potential biomarkers of macrophage activity in macrophage mediated diseases (glomerulonephritis, atherosclerosis, wound healing and cancer) to establish the phenotype, function and balance of M1 and M2 macrophage functional subsets throughout the pathogenesis of these diseases to provide pointers as to the most effective therapeutic strategies to manipulate macrophage activity and restore tissue homeostasis.

When tissues are wounded, direct current extracellular electric fields are established. Moreover synthetically applied electric fields can speed up healing and reduce inflammation in chronic wounds. The group is also determining how small electric fields, influence the polarisation and antibacterial/wound reparative properties of macrophages and activation and proliferation of T cell subsets.

A third area of research is determining how manipulating immune cell function, for example using clinical drugs, can change the susceptibility to infection and the pathways essential for this. For example, we are currently researching and have shown that inhibition of PTP1B is important in regulating infection susceptibility to Candida albicans.

Research Grants

The role of macrophage SOCS3 in the pathogenesis of renal disease. Kidney Research UK. 2013-15.                                                       

The role of sphingolipids in monocyte binding: a potential therapeutic target in restenosis. British Heart Foundation 2013-2016                            

Effects of Dietary Methionine Restriction on Kidney Pathology and Insulin NHS Grampian Endowment Funds. 2014-2015  

Effects of protein tyrosine phosphatase 1B (PTP1B) inhibition on inflammation and atherosclerosis development. British Heart Foundation 2015-2017                        

Monocyte subset markers as biomarkers in asthma . NHS Grampian Endowment Funds. 2015-2016 

Electrical stimulation to enhance macrophage function and accelerate wound healing NHS Grampian Endowment Funds. 2015-2016

PTP1B Inhibition: A potential new target in the treatment of atherosclerosis. NHS Grampian Endowment Funds. 2015-2016                                                                                  

A study into the inflammatory mechanisms and protracted recovery of tako-tsubo cardiomyopathy. BHF Project Grant; 2016-2019;

Interleukin-27 responses in inflammatory bowel disease - a potential new therapeutic? CIRCA PhD studentship; 2016-2020

New treatments for diabetic nephropathy. NHS Grampian Endowment Funds. 2017-2018,

 Interleukin 27 (IL-27) as a new therapy for inflammatory bowel disease-defining IL-27 evoked responses in the gastrointestinal epithelial barrier. NHS Grampian Endowment Funds. 2017-2018,

Unravelling the role of innate cell PTP1B in controlling susceptibility to fungal infection.  ISSF@Aberdeen Seedcorn Award.

Inhibiting angiogenesis in human aortic valves: a new therapeutic target. British Heart Foundation studentship 2017-2020.

The role of innate cell PTP1B in susceptibility to infection. EastBio DTP studentship. 2017-2021

The role of HMBG1 in the pathogenesis of colorectal cancer. Friends of Anchor. 2017-2018

Inhibition of macrophage protein tyrosine phosphatase 1B (PTP1B) as a novel therapy for improved wound healing in diabetes. Diabetes UK 2017-2019

Stress-induced heart disease G17.10 Tenovus 2017-2018

Clinical benefits and mechanism of action of shock wave therapy for healing chronic venous ulcers. NHS Grampian Endowment Funds. 2018-2019

Using potential antigen-specific regulatory T cells as a novel therapeutic strategy to ameliorate autoimmune uveitis. Fight for Sight 2018-2020

Development of potential new diagnostics and therapies for sickle cell anaemia. Friends of Anchor 2018-2020.

2012-2016. Medical Research Scotland -Novel small molecule modulators of the antioxidant response pathway: potential for therapy in cancer/inflammatory disease.

2006-2010. Medical Research Council - Deviating macrophage activation in glomerulonephritis by SOCS proteins.

Teaching

Teaching Responsibilities

 

Year1 MBChB (medicine) Science for Medicine

Year 1 MBChB (medicine) Student selected component (Immunology & Infection) co-ordinator

BI25M7 Energy for Life

IM3501 Fundamentals of Immunology (deputy course co-ordinator)

IM3502 Applied Immunology - Human Health (deputy course co-ordinator)

Honours Immunology IM4007- Immunity and infection - course coordinator

Honours Immunology IM4005-Current Topics in Immunology-course coordinator

IM4006 current research in immunology - course coordinator

Honours Project Supervisor/examiner/tutor

MSc Immunology in Health and Disease

Further Info

External Responsibilities

Committees: Elected member of Renal Association, renal scientists working party (elected 2005 for 5 years) and education and training committee (2010)

Editorial Boards: Frontiers in Immunology, World Journal of Immunology

Ad hoc reviewer -Kidney International, Experimental Cell Research, Nephron-Experimental Nephrology, Journal of Leukocyte Biology, British Journal of Pharmacology, Journal of Immunology, European Journal of Neurology, Journal of Cellular and Molecular Medicine, Journal of Vascular Research, Journal of American Society of Nephrology.

Grant reviewer: Wellcome Trust, Medical Research Council (MRC), Heart Research UK, Medical Research Scotland 

Admin Responsibilities

Foresterhill Biological Safety committe chair

Academic line manager

Programme co-lead Immunity and infection

 

Potential PhD projects

SOCS3 expressing macrophages - a novel target for autoimmune and inflammatory disease

More specific and effective treatments for patients with progressive kidney disease are urgently required. Macrophages are a key feature in inflammatory diseases such as renal inflammation and atherosclerosis. Macrophages can cause tissue injury but are also important in repairing injured tissue. We aim to identify key molecules that switch macrophage function so instead of causing inflammation they promote healing. We have identified SOCS3 as one novel molecule and now we will establish whether manipulation of human macrophages via SOCS3 can reduce their pro-inflammatory properties and translate into important new therapies to treat susceptible patients.

Electric fields-novel regulators of immune cell responses

Tissue injury results in the generation of small endogenous EF, and recently these have been shown to be critical for wound healing via electrotaxis of cells such as epithelial cells and fibroblasts. Immune cells infiltrate sites of inflammation or tissue damage and therefore are also potential targets of EFs. The goals of the project are to characterise the responses of macrophages and T helper (Th) cells, two key immune cells that adopt either pro- or anti-inflammatory properties, to external EFs, and the immunological consequences of this in vivo. These studies will yield important new insights into the basic mechanisms underlying the role of EFs in directing the functional properties of immune cells and establish whether enhancing EFs provides a novel method for modulating their destructive, reparative or immunoregulatory properties.

The role of immune cell PTP1B in susceptibility to fungal infection.

Unravelling the molecular mechanisms and factors that regulate immune responses to fungi is critical for development of novel therapies to alleviate fungal infection. Host cells express pattern recognition receptors that sense the pathogen-associated molecular patterns (PAMPs) in fungi. However, the molecules controlling intracellular signalling mechanisms and outputs are unclear at present. In preliminary experiments, we have discovered a novel intracellular signalling molecule, protein tyrosine phosphatase 1B (PTP1B) that appears to play a role2. Knock out of this molecule, specifically in myeloid cells (neutrophils/monocytes/macrophages/dendritic cells) (LysM PTP1b-/-) renders mice more susceptible to systemic fungal (Candida albicans) infection. Research into the role of PTP1B in controlling immune responses and protecting against fungal infection is at an exciting stage. The aim of the studentship is now to fully characterise immune responses to fungal infection, focussing on PTP1B inhibited myeloid cells, either using clinical PTP1B inhibitors or bone marrow derived cells from LysM PTP1B-/- mice. We will compare the response of PTP1B inhibited/silenced immune cells to infection with Candida albicans with that of cells with intact PTP1B activity. The results will generate important data for driving the direction of this research in future studies and whether the PTP1B clinical inhibitors, currently in trials for breast cancer and diabetes, can change the susceptibility of patients to fungal infection.

 

Publications

Publications