Dr Sharon Dewitt

Lecturer

School of Dentistry

Mae'r cynnwys hwn ar gael yn Saesneg yn unig.

Research theme

Oral and biomedical sciences

Research group

Matrix Biology and Tissue Repair

Research interests

The focus of my research is to identify the early cellular events that occur in disease processes such as arthritis. These early events can then be exploited as indicators of disease to enable early diagnosis and treatment; or as a means of manipulation and modification of the disease process.

Associated research within the School of Dentistry is focused on how extracellular matrix guides cellular responses in physiological processes but also how alterations in its constituents contribute to major diseases including arthritis.

Areas of expertise:

  • Calcium imaging
  • Confocal microscopy
  • Single cell Imaging
  • Image analysis and 3D Reconstruction (Imaris)
  • Neutrophil biology
  • Micromanipulation
  • Microinjection (SLAM)

Selected projects

Medical Research Council

Control of neutrophil infiltration into inflamed airways in chronic obstructive pulmonary disease.

Background: This is a jointly funded PhD Studentship awarded by MRC and British Lung Foundation as part of the MRC Capacity Building Studentship Competition (with MB Hallett)

Aims: To investigate the cell biological mechanism by which neutrophils infiltrate into inflamed airways and especially to establish the role of mu-calpain activation as a step common in neutrophils extravasation

Wellcome Trust

Leukocyte trafficking in calpain-1 null mice.

Background: Calpain-1 is a cytosolic Ca2+-activated protease implicated in cellular adhesion and motility, and specifically in immune cells including neutrophils and lymphocytes. The evidence accumulating for the signalling role of calpain-1, however, has largely depended on pharmacological inhibition. It is therefore important to establish the biology of cells from genetically-modified animals which do not express calpain-1 (with MB Hallett and AS Williams).

Aims: To establish whether a reduction in experimentally-induced inflammatory cell trafficking can be demonstrated in calpain-1 deficient animals

Wellcome Trust

The role of calpain in the control of phagocytosis by neutrophils.

Background: Phagocytosis of microbes by neutrophils is an important event in combating infection. Surprisingly, the mechanism by which phagocytosis occurs is not fully understood. Evidence has accumulated that Ca2+ activation of mu- calpain plays a role in neutrophil phagocytosis (with MB Hallett).

Aims: To establish the role of calpain activation during phagocytosis by neutrophils and establish the molecular events leading to membrane expansion as a permissive step in phagocytosis.

Career profile

1999: First degree in Pharmacology, UWCM

2003: PhD from the University of Wales College of Medicine, Cardiff (Phagocytosis by Neutrophils: The Roles of Ca2+)

2004;   2010: Wellcome Trust funded Postdoctoral role in the Neutrophil Signalling Group, Cardiff University to investigate the mechanisms of neutrophil function

Awarded a Wellcome Trust VIP award to further research in neutrophil phagocytosis.

Successful co-applicant of a Wellcome Trust grant, investigating the role of calpain in the control of phagocytosis by neutrophils (with Prof. MB Hallett).

Successful co-applicant for a PhD studentship awarded by the MRC and British Lung Foundation as part of the MRC Capacity Building Studentship Competition (with Prof. MB Hallett).

2010: ARC Cardiff Academic Fellowship (Cardiff University, School of Dentistry) working with Prof Aeschlimann and the ARCBBC team to develop biomarker assays that predict pathology, pain, inflammation and changes in joint function in musculoskeletal diseases

2015: Appointment to Lecturer in School of Dentistry, Cardiff University

Teaching profile

Postgraduate supervision:

PhD Co-supervisor:

  • Control of neutrophil infiltration into inflamed airways in chronic obstructive pulmonary disease
  • Cytosolic signalling and behaviour of oral neutrophils
  • Regulation of calpain activity in human neutrophils.

PhD Supervisory Team:

  • Signalling shut-down in apoptotic neutrophils

Undergraduate teaching:

Year 2 (Bioscience) BI2251 Cellular and Molecular Aspects of Blood.

Year 2 BDS: Oral Ecosystems

ME3031 Undergraduate Research Project Supervision (co-supervisor).

Awards / Prizes

Grants awarded

Medical Research Council Control of neutrophil infiltration into inflamed airways in chronic obstructive pulmonary disease. Capacity Building Studentship (MB Hallett & S Dewitt) 2008-2011.

Wellcome Trust Leukocyte trafficking in calpain-1 null mice. Knockout Mouse Funding Committee (MB Hallett, S Dewitt, AS Williams) 2007.

Wellcome Trust The role of calpain in the control of phagocytosis by neutrophils (S Dewitt & MB Hallett) 2006-2010.

Wellcome Trust Visualisation and manipulation of calpain activity in human neutrophils. Value In People (VIP) Award (S Dewitt) 2004

UWCM Research Initiative Visualisation and manipulation of calpain activity in human neutrophils (S Dewitt) 2004

Personal awards

Wellcome Trust Value In People (VIP) Award, UWCM. April 2004.

Research Initiative Award, UWCM. April 2004.

1st Prize Oral Presentation at the UWCM 16th Annual Postgraduate Research Day, 2001.

Presentations:

American Society of Cell Biology 46th Annual Meeting, San Diego, 2006. &lcirc; -Calpain Activation and Re-distribution in Myeloid Cells Induced by Elevated Cytosolic Free Ca2+ and Phagocytosis

Infection, Immunity and Inflammation IRG Annual Meeting, Principality Stadium Cardiff, 2006. Regulation of neutrophil infiltration into rheumatoid joints by mu-calpain

ASCB San Francisco 45th Annual Meeting, 2005. Localised PI(3,4,5)P3 at the Phagocytic Cup in HL60 Neutrophils.

European Society Clinical Investigation Meeting, Utrecht 2004. Calpain activity during beta-2 integrin-mediated phagocytosis.

Biochemical Society, Calcium Oscillations and the 5th UK Calcium Signalling Conference, Liverpool 2003. Multi-component Ca2+ signalling accompanies phagocytosis by neutrophils.

Royal Microscopical Society Annual Cell Biology and Histochemistry Meeting, London 2003. Complex Ca2+ signalling in neutrophils co-ordinates their phagocytic and oxidative activity.

UWCM 16th Annual Postgraduate Research Day, 2001. Cytosolic free Ca2+ changes and calpain activity are required for integrin-accelerated phagocytosis by neutrophils.

UWCM 15th Annual Postgraduate Research Day, 2000. Dissecting neutrophil phagocytosis: The role of Ca2+ signalling.

Year 2 BDS: Oral Ecosystems