MRC Centre for Inflammation Research
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Professor Sarah Walmsley

Sarah Walmsley's research focuses on the regulation of neutrophil apoptosis by hypoxia.

Professor Sarah Walmsley

Chair of Respiratory Medicine

  • MRC Centre for Inflammation Research
  • Research Theme: Tissue Remodelling and Regeneration

Contact details

Group Members

  • Patricia Coelho - Research Fellow
  • Rebecca Dickinson - MRC Clinical Research Training Fellow
  • Cathy Doherty - Research Assistant
  • Alison Harris - Postdoctoral Research Fellow
  • Ananda Mirchandani - Wellcome Postdoctoral Clinical Fellow
  • Fiona Murphy - Research Fellow
  • Tracie Plant - ECAT Fellow (jointly with Professor Moira Whyte)
  • Eilise Ryan – Clinical Research Fellow
  • Pranvera Sadiku - Research Fellow
  • Emily Watts - Clinical Research Fellow (jointly with Professor Moira Whyte)
  • Joseph Willson - EPSRC and MRC CDT in Optical Medical Imaging PhD student
  • Rob Grecian - CRUK ECAT Fellow
  • Jessie-May Morgan - OPTIMA PhD student

Research Overview

To date there are no effective treatments for neutrophilic inflammation which is central to the pathology of a number of important respiratory diseases including COPD, bronchiectasis and ARDS. Neutrophils as key effectors of the innate immune response are required to function at sites of inflammation that are relatively oxygen deplete – hypoxic. Unique to the neutrophil hypoxia is a profound survival stimulus. Neutrophils both sense oxygen and respond to changes in oxygenation via the HIF pathway, which involves regulation of the transcription factor hypoxia inducible factor (HIF) by von Hippel Lindau protein and a group of oxygen sensitive hydroxylases – prolyl hydroxylase domain (PHD) containing enzymes and factor inhibiting HIF (FIH). Preliminary data suggest a direct role for this oxygen sensing pathway in the regulation of neutrophil apoptosis at sites of hypoxia. I aim to elucidate the mechanisms regulating HIF-1alpha expression in neutrophils and determine the importance of these pathways for neutrophilic inflammation in vivo.

Current Projects

  • Regulation of neutrophilic inflammation by the HIF/PHD pathway
  • Neutrophil energetics and oxygen sensing
  • The role of hypoxia in determining cellular outcomes to pulmonary infection and its importance in the pathogenesis of COPD
  • The role of Sema3F in regulating neutrophil recruitment and retention at sites of inflammation
  • How does hypoxia, via the HIF pathway, regulate neutrophil activation and survival

Biographical Profile

I am a medical graduate of Edinburgh University.  My current position is Wellcome Senior Clinical Fellow, University of Edinburgh; Honorary Reader and Honorary Consultant in Respiratory Medicine.  I previously held a Wellcome Intermediate Clinical Fellowship with Professor Moira Whyte, University of Sheffield and prior to that held a MRC Training Fellowship with Professor Edwin Chilvers in the Division of Respiratory Medicine, University of Cambridge.  My research focuses on the regulation of neutrophil apoptosis by hypoxia.

I am a Wellcome Senior Clinical Fellow and practising Respiratory Physician.  Following a MRC Training Fellowship in Cambridge during which I obtained my PhD, I moved to the University of Sheffield where I was awarded a Wellcome Intermediate Clinical Fellowship. This enabled me to develop my research programme under the sponsorship of Professor Moira Whyte and complete my specialist clinical training in Respiratory Medicine, culminating in my award of a Wellcome Senior Clinical Fellowship and my move to the MRC/University of Edinburgh Centre for Inflammation Research.  My research focuses on defining how oxygen sensing and metabolic regulation influence phagocyte host defence. More specifically through a better understanding of the mechanisms by which hypoxia regulates key neutrophil functions and survival responses, I aim to validate the therapeutic potential of selective manipulation of these pathway in patients with chronic neutrophil-dominant inflammatory lung diseases.

Publications

Hypoxia determines survival outcomes of bacterial infection through HIF-1α–dependent reprogramming of leukocyte metabolism. Science Immunology  10 Feb 2017:Vol. 2, Issue 8, DOI: 10.1126/sciimmunol.aal2861

 

Sources of Funding

More information on funding at Sarah Walmsley's Research Explorer profile.