Dr Sarah Walmsley MRCP PhD

Department of Infection and Immunity
K Floor
The University of Sheffield Medical School
Beech Hill Road
Sheffield
S10 2RX
United Kingdom

Tel: +44(0) 114 271 1725
Fax: +44(0) 114 271 3892
Email: s.walmsley@sheffield.ac.uk

Biography

I am a medical graduate of Edinburgh University.  My current position is Wellcome Senior Clinical Fellow, University of Sheffield; Honorary Senior clinical Lecturer and Honorary Consultant in Respiratory Medicine. I previously held a Wellcome Intermediate Clinical Fellowship with Professor Moira Whyte 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.

Research Interests

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.

Teaching Interests

I currently mentor a group of final year medical students and help with under graduate clinical training as part of their introduction to clinical skills and during their attachment to medical firms on the respiratory wards.

Professional Activities

Grants that I currently hold:

Regulation of neutrophilic inflammation by the HIF/PHD pathway.
Wellcome Trust Senior Research Fellowship in Clinical Science.
09/2012-08/2017
£1,811,427

Mechanisms and consequences of neutrophil survival in hypoxia.
Wellcome Trust Intermediate Fellowship
05/2006 – 11/2011
£741,138

In vivo regulation of neutrophil function by hypoxic signalling.
Co-supervisor on a Wellcome trust project grant
01/08/2007-31/07/2010
£188,853

The role of HIF-2 in neutrophilic inflammation
Supervisor on an MRC Clinical Research Training Fellowship
06/08/2009-05/08/2012
£254,412

An investigation of myeloid cell pro-inflammatory functions in patients with pulmonary hypertension
NIHR CVBRU funded 4 year PhD studentship
01/10/2008-30/09/2012
£86,268

Current Projects

• Mechanisms and consequences of neutrophil survival in hypoxia.
• The role of HIF-2 in neutrophilic inflammation.
• Investigation of myeloid cell pro-inflammatory functions in patients with pulmonary hypertension.
• Using zebra fish to investigate the molecular control of hypoxic signalling during inflammation.

Key Publications

1. Elks PM, van Eeden FJ, Dixon G, Wang X, Ingham PW, Whyte MKB, Walmsley SR, Renshaw SA.  HIF-1alpha delays inflammation resolution by promoting neutrophil persistence in a zebrafish inflammation model.  Blood 2011; 118:712-722.
2. Walmsley SR, Chilvers ER, Thompson AAR, Vaughan K, Marriott HM, Parker LC, Shaw G, Parmar S, Schneider M, Sabroe I, Dockrell DH, Milo M, Taylor CT, Johnson RS, Pugh CW, Ratcliffe PJ, Maxwell PH, Carmeliet P, Whyte MKB. Prolyl hydroxylase PHD3 is essential for hypoxic regulation of neutrophilic inflammation in humans and mice. J. Clin. Invest. 2011. doi: 10.1172/JCI43273. [Epub ahead of print].
3. Walmsley SR, Cowburn AS, Clatworthy MR, Morrell NW, Roper EC, Singleton V, Maxwell P, Whyte M, Chilvers ER. Neutrophils from patients with heterozygous germline mutations in the von Hippel Lindau protein (VHL) display delayed apoptosis and enhanced bacterial phagocytosis. Blood 2006; 108:3176-3178.
4. Walmsley SR, Print C, Farahi N, Peyssonnaux C, Johnson RS, Cramer T, Sobolewski A, Condliffe A, Cowburn AS, Johnson N, Chilvers ER. The role of HIF-1alpha and NF-kappaB in hypoxia-induced survival in human and murine neutrophils. J. Exp. Med. 2005; 201:105-115.
5. Walmsley SR, Cadwallader K, Chilvers ER. The role of HIF-1alpha in myeloid cell inflammation. Trends in Immunol. 2005; 26:434-439.
6. Mecklenburgh KI and Walmsley SR joint first author, Cowburn AS, Wiesener M, Reed BJ, Upton PD, Deighton J, Greening AP, Chilvers ER. Involvement of a ferroprotein sensor in hypoxia-mediated inhibition of neutrophil apoptosis. Blood 2002; 100 (8): 3008-16.