Professor David Dockrell MD FRCPI FRCP(Glas) FACP
Professor of Infectious Diseases
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 Susan 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. Investigation of apoptosis link closely 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.
- 2013- MRC Clinical Training and Development panel (Clinical Fellowship panel)
- 2012- Academic Director Communicable Diseases Sheffield teaching Hospitals
- 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 advisory panel member
- 2010- Member of the Commission on Human Medicines - Anti Infectives/AIDS/Hepatology Expert Advisory Group
- 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)
- Investigation of respiratory viruses in vivo and their impact on the innate response to bacterial infection (with Prof. Ian Sabroe)
- Investigation of how pneumonia modulates the atherosclerotic plaque and the role of macrophages in this response (MRC training fellowship to Dr Rohit Bazaz jointly supervised with Dr Sheila Francis, Cardiovascular science)
- 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 (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
For Key Publications see below. For a full list of publications click here.
- Prince LR, Maxwell NC, Gill SK, Dockrell DH, Sabroe I, McGreal EP, Kotecha S & Whyte MK (2014) Macrophage phenotype is associated with disease severity in preterm infants with chronic lung disease.. PLoS One, 9(8), e103059. View this article in White Rose Research Online
- Dénes A, Pradillo JM, Drake C, Sharp A, Warn P, Murray KN, Rohit B, Dockrell DH, Chamberlain J, Casbolt H, Francis S, Martinecz B, Nieswandt B, Rothwell NJ & Allan SM (2014) Streptococcus pneumoniae worsens cerebral ischemia via interleukin 1 and platelet glycoprotein Ibα. Annals of Neurology, 75(5), 670-683.
- Aberdein JD, Cole J, Bewley MA, Marriott HM & Dockrell DH (2013) Alveolar macrophages in pulmonary host defence the unrecognized role of apoptosis as a mechanism of intracellular bacterial killing.. Clin Exp Immunol, 174(2), 193-202.
- Dodd MC, Collini PJ & Dockrell DH (2013) Low concordance with HIV testing guidelines in a retrospective review of intensive care practice.. Thorax, 68(11), 1072-1074.
- Basran A, Jabeen M, Bingle L, Stokes CA, Dockrell DH, Whyte MK, Walmsley SR, Higgins KR, Vogel SN, Wilson HL, Prince LR, Prestwich EC, Sabroe RA, Parker LC & Sabroe I (2013) Roles of neutrophils in the regulation of the extent of human inflammation through delivery of IL-1 and clearance of chemokines.. J Leukoc Biol, 93(1), 7-19.
- Dockrell DH, Whyte MK & Mitchell TJ (2012) Pneumococcal pneumonia: mechanisms of infection and resolution.. Chest, 142(2), 482-491.
- (2012) Monocytes regulate the mechanism of T-cell death by inducing Fas-mediated apoptosis during bacterial infection. PLoS Pathogens, 8(7), 30.
- Marriott HM, Daigneault M, Thompson AAR, Walmsley SR, Gill SK, Witcher DR, Wroblewski VJ, Hellewell PG, Whyte MKB & Dockrell DH (2012) A decoy receptor 3 analogue reduces localised defects in phagocyte function in pneumococcal pneumonia. Thorax, 67(11), 985-992.
- McGrath EE, Lawrie A, Marriott HM, Mercer P, Cross SS, Arnold N, Singleton V, Thompson AA, Walmsley SR, Renshaw SA, Sabroe I, Chambers RC, Dockrell DH & Whyte MK (2012) Deficiency of tumour necrosis factor-related apoptosis-inducing ligand exacerbates lung injury and fibrosis.. Thorax, 67(9), 796-803.
- Nelson M, Dockrell D, Edwards S, BHIVA Guidelines Subcommittee , Angus B, Barton S, Beeching N, Bergin C, Boffito M, Breen R, Cartledge J, Clarke S, Fisher M, Freedman A, Gazzard B, Grant A, Greig J, Jones R, Khoo S, Leen C, Lipman M, Manji H, Miller R, Mitchell S, Ong E, Pozniak A, Schmid M, Shiew M, Singer M, Wilkins E, Williams I, Wood C & Weston R (2011) British HIV Association and British Infection Association guidelines for the treatment of opportunistic infection in HIV-seropositive individuals 2011.. HIV Med, 12 Suppl 2, 1-140.
- McGrath EE, Marriott HM, Lawrie A, Francis SE, Sabroe I, Renshaw SA, Dockrell DH & Whyte MK (2011) TNF-related apoptosis-inducing ligand (TRAIL) regulates inflammatory neutrophil apoptosis and enhances resolution of inflammation.. J Leukoc Biol, 90(5), 855-865. View this article in White Rose Research Online
- Bewley MA, Pham TK, Marriott HM, Noirel J, Chu HP, Ow SY, Ryazanov AG, Read RC, Whyte MK, Chain B, Wright PC & Dockrell DH (2011) Proteomic evaluation and validation of cathepsin D regulated proteins in macrophages exposed to Streptococcus pneumoniae.. Mol Cell Proteomics, 10(6), M111.008193. View this article in White Rose Research Online
- Walmsley SR, Chilvers ER, Thompson AA, 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 MK (2011) Prolyl hydroxylase 3 (PHD3) is essential for hypoxic regulation of neutrophilic inflammation in humans and mice.. J Clin Invest, 121(3), 1053-1063. View this article in White Rose Research Online
- Bewley MA, Marriott HM, Tulone C, Francis SE, Mitchell TJ, Read RC, Chain B, Kroemer G, Whyte MK & Dockrell DH (2011) A cardinal role for cathepsin d in co-ordinating the host-mediated apoptosis of macrophages and killing of pneumococci.. PLoS Pathog, 7(1), e1001262. View this article in White Rose Research Online
- Collini P, Noursadeghi M, Sabroe I, Miller RF & Dockrell DH (2010) Monocyte and macrophage dysfunction as a cause of HIV-1 induced dysfunction of innate immunity.. Curr Mol Med, 10(8), 727-740. View this article in White Rose Research Online
- Webster SJ, Daigneault M, Bewley MA, Preston JA, Marriott HM, Walmsley SR, Read RC, Whyte MK & Dockrell DH (2010) Distinct cell death programs in monocytes regulate innate responses following challenge with common causes of invasive bacterial disease.. J Immunol, 185(5), 2968-2979.
- Daigneault M, Preston JA, Marriott HM, Whyte MK & Dockrell DH (2010) The identification of markers of macrophage differentiation in PMA-stimulated THP-1 cells and monocyte-derived macrophages.. PLoS One, 5(1), e8668. View this article in White Rose Research Online
- Marriott HM, Jackson LE, Wilkinson TS, Simpson AJ, Mitchell TJ, Buttle DJ, Cross SS, Ince PG, Hellewell PG, Whyte MK & Dockrell DH (2008) Reactive oxygen species regulate neutrophil recruitment and survival in pneumococcal pneumonia.. Am J Respir Crit Care Med, 177(8), 887-895. View this article in White Rose Research Online
- Prince LR, Bianchi SM, Vaughan KM, Bewley MA, Marriott HM, Walmsley SR, Taylor GW, Buttle DJ, Sabroe I, Dockrell DH & Whyte MK (2008) Subversion of a lysosomal pathway regulating neutrophil apoptosis by a major bacterial toxin, pyocyanin.. J Immunol, 180(5), 3502-3511. View this article in White Rose Research Online
- Bianchi SM, Prince LR, McPhillips K, Allen L, Marriott HM, Taylor GW, Hellewell PG, Sabroe I, Dockrell DH, Henson PW & Whyte MK (2008) Impairment of apoptotic cell engulfment by pyocyanin, a toxic metabolite of Pseudomonas aeruginosa.. Am J Respir Crit Care Med, 177(1), 35-43. View this article in White Rose Research Online