Professor David Dockrell

MD FRCPI FRCP(Glas) FACP

Department of Infection, Immunity and Cardiovascular Disease

Honorary Professor of Infection Medicine

Profile

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 moved from Sheffield in 2016 to become Professor of infection Medicine at the University of Edinburgh with an interest in HIV medicine and infections in immunocompromised hosts.

Research interests

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.

My 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.

I am 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.

My work interdigitates closely with that of Professor Moira Whyte (University of Edinburgh), investigation of myeloid cell biology and the regulation of pulmonary inflammation and pulmonary disease with Professor Ian Sabroe (University of Sheffield) and Professor Moira Whyte, and studies on in vivo models of inflammation with Dr Helen Marriott. Our proteomic studies are carried out with Prof Mark Dickman and formerly also with Phillip Wright (Chemical and Process Engineering).

Current Projects:

  • NIHR Global Health Research Unit on Respiratory Health (RESPIRE), University of Edinburgh (PI A. Sheikh and H. Campbell) Co-I Aug 2017- March 21. £6, 998,487 GHR Group 16/136/109
  • NIHR Global Health Research Unit on Mucosal Pathogens (MPRU), University College London (PI R. Heyderman) Co-I June 2017-2021. £6.8 Million. 16/136/46.
Teaching interests

My teaching focuses on the pathogenesis and clinical features of HIV and other infectious diseases.

Professional activities
  • UKRI Future Leaders Fellowship panel 2018-
  • National PhD Training Programme in AMR Management Committee 2017-
  • MRC NW Clinical Pharmacology Training Panel, Chair 2017-
  • DFG (German research foundation) Advisory Board for Research Centre Innate Immunity in the Lung SFB Transregio 84 2018-
  • Wellcome-HRB Irish Clinical Academic Training Programme External Panel Member and Advisory Board 2017-
  • National PhD Training Programme in AMR Management Committee 2017-
  • MRC NW Clinical Pharmacology Training Panel, Chair 2017-
  • DFG (German research foundation) Advisory Board for Research Centre Innate Immunity in the Lung SFB Transregio 84 2018-
  • Wellcome-HRB Irish Clinical Academic Training Programme External Panel Member and Advisory Board 2017-

Editorial Positions:

  • Am J Physiol Lung
  • Current Opinion in Infectious diseases (HIV)
Key publications
  1. Kitchen GB, Hopwood T, Baxter M, Poolman T,  Hussell T, Begley N, Mathews L, Dockrell DH, Gibbs J, Cunningham P, Durrington H, Blaikley J, Loudon A, Ray DW. The clock gene Bmal1 inhibits macrophage motility, phagocytosis, and impairs defence against pneumonia. Proceedings of the National Academy of Sciences of the United States of America. 2020: 117; 1543-51.
  2. B. Li B, Clohisey S, Chia BS, Wang B, Cui A, Eisenhaure T, Schweitzer L, Hoover P, Parkinson N, Nachshon A, Smith N, Regan T, Farr D, Gutmann M, Irfan B, Law A, Sangesland M, Gat-Viks I, Digard P, Shobha V, Lingwood D, Dockrell D, Doench J, Baillie J, and Hacohen N. Genome-wide CRISPR screen Identifies Host Dependency Factors for Influenza A Virus Infection. Nature Communications 2020:11; 164.
  3. Hughes B, Burton C, Reese A, Jabeen M, Wright C, Wright J, Khoshaein N, Marsh E, Peachell P, Sun S-C, Dockrell D, Marriott HM, Sabroe I, Condliffe AM, Prince l . Pellino-1 regulates immune responses to Haemophilus influenzae in models of inflammatory lung disease.  Frontiers Immunology 2019: 10 (1721) 1-12 doi10.3389/fimmu.2019.01721.
  4. Belchamber KBR, Singh R, Batista CM, Whyte MK, Dockrell DH, Kilty I, Robinson MJ, Wedzicha JA, Barnes PJ, Donnelly LE, COPDMAP consortium. Defective bacterial phagocytosis is associated with dysfunctional mitochondria in COPD macrophages. European Respiratory Journal 2019: doi 10.1183/13993003.02244-2018. PMID 31320451.
  5. Cole J, Hanson EJ, James DC, Dockrell DH, Dickman MJ. Comparison of data acquisition methods for the identification and quantification of histone post-translational modifications on a Q Exactive HF hybrid quadrupole Orbitrap mass spectrometer. Rapid Communications in Mass Spectrometry 2019 : 33; 897-906.
  6. Preston JA, Bewley MA, Marriott HM, Houghton AM, Mohasin M, Jubrail J, Morris L, Stephenson YL, Cross S, Greaves DR, Craig RW, Nico van Rooijen N, Bingle CD, Read RC, Mitchell TJ, Whyte MKB, Shapiro SD and Dockrell DH. Alveolar macrophage apoptosis-associated bacterial killing helps prevent murine pneumonia. American Journal of Respiratory and Critical Care Medicine 2019: 200; 84-97 doi: 10.1164/rccm.201804-0646OC. PMID 30649895
  7. Bewley MA, Budd RC, Ryan E, Cole J, Collin Pi, Marshall J, Kolsum U, Beech G, Emes RD, Tcherniaeva I, Berbers GAM, Walmsley SR, Donaldson G, Wedzichia JA, Kilty J, Rumsey W, Sanchez Y, Brightling CE, Donnelly LE, Barnes PJ, SinghDJ, Whyte MKB, Dockrell DH . Opsonic phagocytosis in chronic obstructive pulmonary disease is enhanced by Nrf2 agonists.  American Journal of Respiratory and Critical Care Medicine 2018 in press doi: 10.1164/rccm.201705 0903OC. PMID:29547002.
  8. Boldock E, Surewaard BGJ, Shamarina D, Na M, Fei Y, Ali A, Williams A, Pollitt EDJ, Szkuta P, Morris P, Prajsnar TK, McCoy KD, Jin T, Dockrell DH, van Strijp JAG, Kubes P, Renshaw SA, Foster SJ. Human skin commensals augment Staphylococcus aureus pathogenesis. Nature Microbiology 2018: 3; 881-90.
  9. Collini PJ, Bewley MA, Mohasin M, Marriott HM, Miller RF, Gerretti AM, Beloukas A, Papadimitropoulos A, Read RC, Noursadeghi M, Dockrell DH. HIV gp120 in lungs of ART-treated individuals impairs alveolar macrophage responses to pneumococci. American Journal of Respiratory and Critical Care Medicine 2018 : 197; 1604-15.
  10. Sadiku P, Wilson JA, Dickinson RS, Murphy F, Harris AJ, Lewis A, Sammut D, Mirchandani AS, Ryan E, Watts ER, Thompson AAR, Marriott HM, Dockrell DH, Taylor, CT, Schneider M, Maxwell PH, Chilvers EH, Mazzone M, Moral V, Pugh CW, Ratcliffe PJ, Schofield CJ, Ghesquiere B, Carmeliet P, Whyte MK, Walmsley SR. Prolyl hydroxylase 2 inactivation enhances glycogen storage and promotes excessive neutrophilic responses. J. Clin. Invest. 2017: 127; 3407-20. doi: 10.1172/JCI90848
  11. Salamaga B, Prajsnar TK, Jareño-Martinez A, Willemse J, Bewley MA, Chau F, Belkacem B, Meijer AH, Dockrell DH, Renshaw SA, Mesnage S. Bacterial size matters: Multiple mechanisms controlling septum cleavage and diplococcus formation are critical for the virulence of the opportunistic pathogen Enterococcus faecalis. PLoS Pathogens. 2017: 13 (7): e1006526. doi: 10.1371/journal.ppat.1006526
  12. Bewley MA, Preston JA, Mohasin M, Marriott HM, Budd RC, Swales J, Collini P, Greaves DR, Craig RW, Brightling CE, Donnelly LE, Barnes PJ, Singh D, Shapiro SD, Whyte MKB, Dockrell DH. Impaired mitochondrial microbicidal responses in chronic obstructive pulmonary disease macrophages. American Journal of Respiratory and Critical Care Medicine 2017: 196; 845-55.
  13. Thompson AAR, Dickinson RS, Murphy F, Thomson JP, Marriott HM, Tavares A, Willson J, Williams L, Lewis A, Mirchandani A, Dos Santos Coelho P, Doherty C, Ryan E, Watts E, Morton NM, Forbes S, Stimson RH, Hameed AG, Arnold N, Preston JP, Lawrie A, Finesguerra V, Mazzone M, Sidikhu P, Goveia J, Taverna F, Carmeliet P, Foster SJ, Chilvers ER, Cowburn AS, Dockrell DH, Johnson RS, Meehan RR, Whyte MKB, Walmsley SA. Hypoxia determines survival outcomes of bacterial infection through HIF-1alpha dependent re-programming of leukocyte metabolism. Science Immunology 2017: 2; 8 pii: eeal2861 doi 10.1126/sciimmunol.aal2861
  14. Jubrail J, Morris P, Bewley MA, Stoneham S, Johnston SA, Foster SJ, Peden AA, Read RC, Marriott HM, Dockrell DH. Inability to sustain intraphagolysosomal killing of Staphylococcus aureus predisposes to bacterial persistence in macrophages. Cellular Microbiology, 2015 18(1), 80-96.
  15. Bewley MA, Naughton M, Preston J, Mitchell A, Holmes A, Marriott HM, Read RC, Mitchell TJ, Whyte MKB, Dockrell DH. Pneumolysin Activates Macrophage Lysosomal Membrane Permeabilization and Executes Apoptosis by Distinct Mechanisms without Membrane Pore Formation. mBio, 2014 5(5).