Professor David Dockrell MD FRCPI FRCP(Glas) FACP
The University of Sheffield Medical School
Department of Infection and Immunity
Room K127, K Floor
Beech Hill Road
Tel: +44 (0)114 271 2160
Fax: +44 (0)114 271 3892
Secretary - Mrs Sue Clary
Tel: +44 (0)114 226 8961
I am a clinician scientist. My undergraduate degree was from Trinity College Dublin and I then trained in Dublin before undertaking specialty training in Infectious Diseases at the Mayo Clinic, USA. During this period I developed my interests in macrophage immunology and in the regulation of apoptosis.
I joined the University of Sheffield in 1998 and developed my research with a particular focus on how macrophage apoptosis regulates innate immune responses with particular emphasis on pneumococcal infection. In 2005 I received a Wellcome Senior Clinical fellowship.
I am currently a Professor of Infectious Diseases and a consultant in the department of Communicable Diseases at the Royal Hallamshire Hospital with an interest in HIV medicine and infections in immunocompromised hosts.
My research interests stem from understanding how macrophages contribute to the innate immune response against bacteria and viruses. We have developed a variety of tissue culture models as well as several in vivo models using the pneumococcus as a probe. We have applied these to a variety of other infections including Staphylococcus aureus, Neisseria meningitidis and Pseudomonas aeruginosa as well as HIV-1 and Influenza A virus infection. In particular we are investigating how the host response can utilize induction of apoptosis to enhance microbial killing and regulation of the inflammatory response and how this can be manipulated by specific pathogens.
Our current work focuses on understanding how microbial killing in organelles such as the phagolysosome sensitizes the macrophage to initiate a programme of apoptosis which involves downregualtion of the anti-apoptotic Bcl-2 family member Mcl-1 and ultimately leads to a mitochondrial pathway of apoptosis. We investigate how macrophage phenotype or specific pathogens can alter this host response.
We are also interested in how clinical diseases may alter susceptibility by modulating macrophage host responses. As part of the MRC-ABPI COPD consortium we are investigating how COPD modifies macrophage responses to respiratory bacteria. Our group also are examining how HIV-1 modifies macrophage responses to pneumococci in the lung.
Our work interdigitates closely with that of colleagues in our department. Studies on macrophage function and the pathogenesis of bacterial infection link closely with those of Prof Robert Read, investigation of apoptosis with Prof Moira Whyte, investigation of myeloid cell biology and the regulation of pulmonary inflammation and pulmonary disease with Prof Ian Sabroe and Prof Moira Whyte, and studies on in vivo models of inflammation with Dr Helen Marriott. Our proteomic studies are carried out in collaboration with Prof Phillip Wright (Chemical and Process Engineering).
I am also research lead for the South Yorkshire and North Trent HIV network and work closely with Dr Christine Bowman in co-ordinating local studies and our participation in national MRC sponsored clinical trials. These focus on the efficacy and complications associated with antiretroviral therapy.
My teaching focuses on the pathogenesis and clinical features of HIV and other infectious diseases.
- 2012- Chair South Yorkshire and Humber CLRN Microbiology and Infection Local Specialty Group
- 2012- External examiner Liverpool School of Tropical Medicine MSc in Infectious Diseases
- 2011/12 - Health Research Board Ireland panel member (2012 Senior clinical fellowship panel)
- 2011- Meningitis UK panel member
- 2010- Medicines and Healthcare Products Regulatory Agency, Member of expert advisory group: Anti-infectives, HIV and Hepatology
- 2009- NIHR Public Health Infections-Scientific Advisory Group
- 2008- Member, British Lung Foundation Scientific Committee
- 2008-10 Member, British HIV Association National Executive and co-editor of National Guidelines on the Management of Opportunistic Infections
- 2007- Member, Scientific Committee for British Infection Society/ Association of Medical Microbiology (Chair 2007-10)
- Mechanisms and consequences of host-mediated macrophage apoptosis in pneumococcal pneumonia.
- A proteomics approach to examine how bacteria inhibit macrophage apoptosis to subvert innate immune responses.
- Investigating the role of HIV infection on the macrophage's apoptotic response to bacterial infection (MRC Training Fellowship to Paul Collini)
- The role of the alveolar macrophage and neutrophils in the pathogenesis of Staphylococcus aureus pneumonia (with Mike Boots as part of the Infectious Disease Cross Cutting Network led by Simon Foster)
- Investigation of mechanisms, impact and therapeutic targeting of microbial colonisation in COPD (with Profs Whyte and Sabroe and MRC-ABPI consortium collaborators)
- American Physiology Lung
- Current Opinion in Infectious Diseases-HIV section
- Monocytes Regulate the Mechanism of T-cell death by Inducing Fas-mediated Apoptosis During Bacterial Infection. M. Daigneault, T.I. de Silva, M.A. Bewley, J.A. Preston, H.M. Marriott, A.M. Mitchell, T.J. Mitchell, R.C. Read, M.K.B. Whyte and D.H. Dockrell. PLoS Pathogens 2012 July: 8 (7); e1002814
- A Decoy Receptor 3 Analogue Reduces Localized Defects in Phagocyte Function in Pneumococcal Pneumonia. H.M. Marriott, M. Daigneault, A.A.R. Thompson, S.R. Walmsley, S.K. Gill, D.R. Witcher, V.J. Wroblewski, P.G. Hellewell, M.K.B. Whyte and D.H. Dockrell. Thorax 2012: 2012: In press
- Roles of neutrophils in the regulation of the extent of human inflammation through delivery of IL-1 and clearance of chemokines. A. Basran, M. Jabeen, L. Bingle, C.A. Stokes, D.H. Dockrell, M.K.B. Whyte, S.R. Walmsley, K.R.Higgins, S.N. Vogel, H.L. Wilson, L.R. Prince, E.C. Prestwich, R.A. Sabroe, L.C. Parker, and I. Sabroe. J. Leukoc Biol 2012:
- Deficiency of Tumour Necrosis Factor-Related Apoptosis-Inducing Ligand Exacerbates Lung Injury and Fibrosis. E.E. McGrath, A. Lawrie, H.M. Marriott, P. Mercer, S.S. Cross, N. Arnold, V. Singleton, A.A. Thompson, S.R. Walmsley, S.A. Renshaw, I. Sabroe, R.C. Chambers, D.H. Dockrell and M.K.B. Whyte. Thorax 2012: 67; 796-803
- IL-1beta regulates CXCL8 release and influences disease outcome in response to Streptococcus pneumoniae, defining intracellular cooperation between pulmonary epithelial cells and macrophages. H.M. Marriott, K.A. Gascoyne, R. Gowda, I. Geary, M.J. Nicklin, F. Iannelli, G. Pozzi, T.J. Mitchell, M.K. Whyte, I. Sabroe and D.H. Dockrell. Infection and Immunity. 2012: 80; 1140-49
- TNF-Related Apoptosis Inducing Ligand (TRAIL) regulates inflammatory neutrophil apoptosis and enhances resolution of inflammation. E.E. McGrath, H.M. Marriott, A. Lawrie, S.E. Francis, I. Sabroe, S.A. Renshaw, D.H. Dockrell and M.K.B. Whyte. Journal of Leukocyte Biology 2011: 90; 855-65
- Proteomic evaluation and validation of cathepsin D regulated proteins in macrophages exposed to Streptococcus pneumoniae M.A. Bewley, T.K. Pham, H. M. Marriott, J. Noirel, H-P. Chu, S. Y. Ow, A.G. Ryzanov, R. C. Read, M.K.B. Whyte, B. Chain, P.C. Wright and D. H. Dockrell Molecular and Cellular Proteomics 2011: 10(6):M111.008193; 1-14
- A Cardinal Role for Cathepsin D in Co-ordinating the Host-mediated Apoptosis of Macrophages and Killing of Pneumococci M. A. Bewley, H. M. Marriott, C. Tulone, S. E. Francis, T. J. Mitchell, R. C. Read, B. Chain, G. Kroemer, M.K.B. Whyte, and D. H. Dockrell PLoS Pathogens 2011: 7 (1) e1001262. doi:10.1371
- Distinct cell death programs in monocytes regulate innate responses following challenge with common causes of invasive bacterial disease. S. J. Webster, M. Daigneault, M. A. Bewley, J. A. Preston, H. M.Marriott, S.R.Walmsley, R.C.Read, M.K.B.Whyte and D.H.Dockrell. Journal of Immunology 2010: 185; 2968-79
- The identification of markers of macrophage differentiation in PMA-stimulated THP-1 cells and monocyte-derived macrophages. M. Daigneault, J. A. Preston, H. M. Marriott, M.K. Whyte, D.H. Dockrell. PLoS One. 2010: 5; e8668
- Reactive oxygen species regulate neutrophil recruitment and survival in pneumococcal pneumonia. H. M. Marriott, L. E. Jackson, T. S. Wilkinson, A. J. Simpson, T. J. Mitchell, D. J. Buttle, S. S. Cross, P. G Ince, P. G. Hellewell, M. K.B. Whyte and D. H. Dockrell. American Journal of Respiratory and Critical Care Medicine 2008: 177; 887-95..
- Dynamic changes in Mcl-1 expression regulate macrophage viability or commitment to apoptosis and are essential for optimal bacterial clearance during pneumococcal infection. H.M. Marriott, C.D. Bingle, R.C. Read, K.E. Braley, R.W. Craig, G. Kroemer, P.G. Hellewell, M.K.B. Whyte and D.H. Dockrell. Journal of Clinical Investigation. 2005: 115; 359-68.