Dimitra Peppa

Associate Professor in HIV immunology/ Honorary Consultant HIV Medicine

Research area

Viral Immunology, NK cell biology and Chronic Inflammation

Research programme

• Viral Immunity

Research summary

The Peppa lab has an interest in chronic viral diseases (HBV, HIV) and emerging viral infections (SARS-CoV-2) of global health significance. People living with HIV and chronic viral hepatitis suffer detrimental health care outcomes associated with immune dysfunction, ongoing inflammation, accelerated ageing and increased vulnerability to emerging infections.

Our aim is to increase our understanding of the role of key immune cell components, that can be harnessed to improve the lives of our patients.

We focus on NK cell immunology, studying their role in the context of viral infections and within distinct anatomical compartments. Through the use of cutting-edge technologies and well curated cohorts of patient samples we systematically examine immune pathways that are preserved or dysregulated during health and viral disease. This represents a critical first step in the identification of new molecular targets for therapies that could aid clinical monitoring, enable stratification of patients for targeted interventions and facilitate the development of NK cell based therapeutics.

Previous contributions include demonstration of the antiviral and rheostat roles of liver-resident and adaptive subsets of NK cells in chronic HBV and HIV infection. This work has provided compelling rationale to optimise approaches to i) elicit broadly neutralising antibodies in HIV during vaccination ii) determine the role of viral infections impacting the development of unique adaptive/memory NK cell subsets especially within tissues and iii) harness and re-direct NK cells with memory characteristics to overcome the current barriers to eliciting effective immunity to viral infections.

A further aim of our lab is to dissect the network of drivers of inflammation and immune dysfunction associated with premature ageing and multi-morbidity in people living with HIV.

Publications

Selected publications

• Touizer E, Alrubayyi A, Rees-Spear C, Fisher-Pearson N, Griffith SA, Muir L, Pellegrino P, Waters L, Burns F, Kinloch S, Rowland-Jones S, Gupta RK, Gilson R, Peppa D, McCoy LE. Failure to seroconvert after two doses of BNT162b2 SARS-CoV-2 vaccine in a patient with uncontrolled HIV. Lancet HIV. 2021 Jun;8(6):e317-e318. doi: 10.1016/S2352-3018(21)00099-0.
• Alrubayyi A, Gea-Mallorquí E, Touizer E, Hameiri-Bowen D, Kopycinski J, Charlton B, Fisher-Pearson N, Muir L, Rosa A, Roustan C, Earl C, Cherepanov P, Pellegrino P, Waters L, Burns F, Kinloch S, Dong T, Dorrell L, Rowland-Jones S, McCoy LE, Peppa D. Characterization of humoral and SARS-CoV-2 specific T cell responses in people living with HIV. bioRxiv [Preprint]. 2021 Feb 16:2021.02.15.431215. doi: 10.1101/2021.02.15.431215.
• Gupta RK, Abdul-Jawad S, McCoy LE, Mok HP, Peppa D, Salgado M, Martinez-Picado J, Nijhuis M, Wensing AMJ, Lee H, Grant P, Nastouli E, Lambert J, Pace M, Salasc F, Monit C, Innes AJ, Muir L, Waters L, Frater J, Lever AML, Edwards SG, Gabriel IH, Olavarria E. HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation. Nature. 2019 Apr;568(7751):244-248. doi: 10.1038/s41586-019-1027-4.
• Bradley T, Peppa D, Pedroza-Pacheco I, Li D, Cain DW, Henao R, Venkat V, Hora B, Chen Y, Vandergrift NA, Overman RG, Edwards RW, Woods CW, Tomaras GD, Ferrari G, Ginsburg GS, Connors M, Cohen MS, Moody MA, Borrow P, Haynes BF. RAB11FIP5 Expression and Altered Natural Killer Cell Function Are Associated with Induction of HIV Broadly Neutralizing Antibody Responses. Cell. 2018 Oct 4;175(2):387-399.e17. doi: 10.1016/j.cell.2018.08.064.
• Peppa D, Pedroza-Pacheco I, Pellegrino P, Williams I, Maini MK, Borrow P. Adaptive Reconfiguration of Natural Killer Cells in HIV-1 Infection. Front Immunol. 2018 Mar 16;9:474. doi: 10.3389/fimmu.2018.00474.
• Huang WC, Easom NJ, Tang XZ, Gill US, Singh H, Robertson F, Chang C, Trowsdale J, Davidson BR, Rosenberg WM, Fusai G, Toubert A, Kennedy PT, Peppa D, Maini MK. T Cells Infiltrating Diseased Liver Express Ligands for the NKG2D Stress Surveillance System. J Immunol. 2017 Feb 1;198(3):1172-1182. doi: 10.4049/jimmunol.1601313.
• Peppa D, Gill US, Reynolds G, Easom NJ, Pallett LJ, Schurich A, Micco L, Nebbia G, Singh HD, Adams DH, Kennedy PT, Maini MK. Up-regulation of a death receptor renders antiviral T cells susceptible to NK cell-mediated deletion. J Exp Med. 2013 Jan 14;210(1):99-114. doi: 10.1084/jem.20121172.

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