Prof Mala Maini

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Personal Profile

Name: Mala Maini Email: m.maini@ucl.ac.uk
Title: Prof Tel: 020 3108 2170
Department: Research Department of Immunology Fax:
Position: Professor of Viral Immunology Address: Rayne Institute, 5 University Street, London, WC1E 6JF
Research Domain: Infection, Immunology & Inflammation, Personalised Medicine Web Page: Personal Web Page

Profile

Research Description

  • Our research programme is focused on dissecting the immune correlates of viral persistence and liver damage in order to allow the development of novel immunotherapeutic strategies for hepatitis B virus (HBV).
  • As well as being of great medical importance in its own right, HBV provides a useful model to provide insights into liver immunology, which has relevance for other hepatotropic infections and malignancies, liver transplantation and autoimmunity.
  • We have become fascinated by how the liver utilises multiple specialised cell types and pathways to maintain a uniquely tolerant immunological environment. Defining the mechanisms of hepatic tolerance is critical to understanding how three of the most prevalent and devastating human pathogens, HBV, hepatitis C virus and malaria, take advantage of this niche in which to replicate and/or persist.
  • We are also interested in how hepatic immune responses mediate and regulate the liver damage that drives fibrosis, ultimately leading to the complications of liver cirrhosis and hepatocellular carcinoma (HCC) that still kill an estimated 600,000 people a year with chronic HBV infection. This is of particular interest in patients co-infected with HBV and HIV who have ongoing high mortality from accelerated liver fibrosis.
  • Existing therapies are rarely able to cure HBV or complications like HCC so our goal is to develop tailored boosting of antiviral immunity. The rationale for this approach is based on the fact that many adults control HBV through their natural immune response without overwhelming liver damage.

Research Activities

Hepatitis-HIV co-infection

Hepatology

Immunopathogenesis of hepatitis B virus infection

Immunoregulation in rheumatic disease

Mechanisms regulating lymphocyte differentiation i

Molecular Virology of Human Hepatitis

Pathogenic Interaction Between Natural Killer (Nk) And T Cells In Chronic Hepatitis B Virus Infection

Viral infections and innate immune reponses

Education Description

I have made substantial contributions to various teaching programmes over the years and have acquired extensive experience in teaching through seminars, interactive tutorials, and one on one in the lab or clinic. I have taught medical students and junior doctors, BSc and MSc students, nurses and physiotherapists, and post-graduates on an Advanced Immunology course.
Currently I teach on the Immunology BSc and Virology BSc courses and supervise undergraduate and postgraduate students in the laboratory.

UCL Collaborators

Prof Dame Linda Partridge; Prof David Gems; Prof William Rosenberg; Prof John Greenwood; Dr Michael Jacobs; Prof Claudia Mauri; Prof Nigel Klein; Prof Arne Akbar; Dr Richard Gilson; Prof Geoffrey Dusheiko; Prof Dominic Withers; Prof David Isenberg; Prof Mike Ehrenstein; Prof Mary Collins; Prof Dame Anne Johnson; Prof Deenan Pillay; Prof Caroline Sabin; Dr Liz Jury

External Collaborators

Publications

    2014

    • Maini MK, Schurich A (2014). Direct - acting antivirals trump interferon - alpha in their capacity to rescue exhausted T cells upon HCV clearance.. J Hepatol, , - . doi:10.1016/j.jhep.2014.06.017

    2013

    • Schurich A, Pallett LJ, Lubowiecki M, Singh HD, Gill US, Kennedy PT, Nastouli E, Tanwar S, Rosenberg W, Maini MK (2013). The third signal cytokine IL-12 rescues the anti-viral function of exhausted HBV-specific CD8 T cells.. PLoS Pathog, 9(3), e1003208 - . doi:10.1371/journal.ppat.1003208
    • Micco L, Peppa D, Loggi E, Schurich A, Jefferson L, Cursaro C, Panno AM, Bernardi M, Brander C, Bihl F, Andreone P, Maini MK (2013). Differential boosting of innate and adaptive antiviral responses during pegylated-interferon-alpha therapy of chronic hepatitis B.. J Hepatol, 58(2), 225 - 233. doi:10.1016/j.jhep.2012.09.029
    • Maini MK, Peppa D (2013). NK cells: a double-edged sword in chronic hepatitis B virus infection.. Front Immunol, 4, 57 - . doi:10.3389/fimmu.2013.00057
    • Peppa D, Gill US, Reynolds G, Easom NJ, Pallett LJ, Schurich A, Micco L, Nebbia G, Singh HD, Adams DH, Kennedy PT, Maini MK (2013). Up-regulation of a death receptor renders antiviral T cells susceptible to NK cell-mediated deletion.. J Exp Med, 210(1), 99 - 114. doi:10.1084/jem.20121172

    2012

    • Protzer U, Maini MK, Knolle PA (2012). Living in the liver: hepatic infections.. Nat Rev Immunol, 12(3), 201 - 213. doi:10.1038/nri3169
    • Nebbia G, Peppa D, Schurich A, Khanna P, Singh HD, Cheng Y, Rosenberg W, Dusheiko G, Gilson R, ChinAleong J, Kennedy P, Maini MK (2012). Upregulation of the Tim-3/galectin-9 pathway of T cell exhaustion in chronic hepatitis B virus infection.. PLoS One, 7(10), e47648 - . doi:10.1371/journal.pone.0047648
    • Maini MK, Schurich A (2012). Platelets harness the immune response to drive liver cancer.. Proc Natl Acad Sci U S A, 109(32), 12840 - 12841. doi:10.1073/pnas.1210296109
    • Das A, Ellis G, Pallant C, Lopes AR, Khanna P, Peppa D, Chen A, Blair P, Dusheiko G, Gill U, Kennedy PT, Brunetto M, Lampertico P, Mauri C, Maini MK (2012). IL-10-producing regulatory B cells in the pathogenesis of chronic hepatitis B virus infection.. J Immunol, 189(8), 3925 - 3935. doi:10.4049/jimmunol.1103139
    • Peppa D, Maini MK (2012). Pathogenesis of hepatitis B virus infection and potential for new therapies.. Br J Hosp Med (Lond), 73(10), 581 - 584.
    • Zhao Q, Peng L, Huang W, Li Q, Pei Y, Yuan P, Zheng L, Zhang Y, Deng J, Zhong C, Hu B, Ding H, Fang W, Li R, Liao Q, Lin C, Deng W, Yan H, Hou J, Wu Q, Xu T, Liu J, Hu L, Peng T, Chen S, Lai KN, Yuen MF, Wang Y, Maini MK, Li C, Li M, Wang J, Zhang X, Sham PC, Wang J, Gao ZL, Wang Y (2012). Rare inborn errors associated with chronic hepatitis B virus infection.. Hepatology, 56(5), 1661 - 1670. doi:10.1002/hep.25850
    • Liu M, Miao T, Zhu H, Symonds AL, Li L, Schurich A, Maini MK, Zhang J, Kennedy PT, Li S, Wang P (2012). IL-2-engineered nano-APC effectively activates viral antigen-mediated T cell responses from chronic hepatitis B virus-infected patients.. J Immunol, 188(3), 1534 - 1543. doi:10.4049/jimmunol.1102709
    • Nebbia G, Peppa D, Maini MK (2012). Hepatitis B infection: current concepts and future challenges.. QJM, 105(2), 109 - 113. doi:10.1093/qjmed/hcr270

    2011

    • Gehring AJ, Koh S, Chia A, Paramasivam K, Chew VS, Ho ZZ, Lee KH, Maini MK, Madhavan K, Lim SG, Bertoletti A (2011). Licensing virus-specific T cells to secrete the neutrophil attracting chemokine CXCL-8 during hepatitis B virus infection.. PLoS One, 6(8), e23330 - . doi:10.1371/journal.pone.0023330
    • Micco L, Peppa D, Loggi E, Schurich A, Carmela C, Panno AM, Bihl F, Bernardi M, Andreone P, Maini MK (2011). PEGYLATED INTERFERON-ALPHA POTENTLY AUGMENTS NK CELL ANTIVIRAL EFFECTOR FUNCTION.
    • Schurich A, Khanna P, Lopes AR, Han KJ, Peppa D, Micco L, Nebbia G, Kennedy PT, Geretti AM, Dusheiko G, Maini MK (2011). Role of the coinhibitory receptor cytotoxic T lymphocyte antigen-4 on apoptosis-Prone CD8 T cells in persistent hepatitis B virus infection.. Hepatology, 53(5), 1494 - 1503. doi:10.1002/hep.24249
    • Gehring AJ, Xue SA, Ho ZZ, Teoh D, Ruedl C, Chia A, Koh S, Lim SG, Maini MK, Stauss H, Bertoletti A (2011). Engineering virus-specific T cells that target HBV infected hepatocytes and hepatocellular carcinoma cell lines.. J Hepatol, 55(1), 103 - 110. doi:10.1016/j.jhep.2010.10.025

    2010

    • Das A, Maini MK (2010). Innate and adaptive immune responses in hepatitis B virus infection.. Dig Dis, 28(1), 126 - 132. doi:10.1159/000282075
    • Hoare M, Gelson WTH, Das A, Fletcher JM, Davies SE, Curran MD, Vowler SL, Maini MK, Akbar AN, Alexander GJM (2010). CD4+ T-lymphocyte telomere length is related to fibrosis stage, clinical outcome and treatment response in chronic hepatitis C virus infection. J HEPATOL, 53(2), 252 - 260. doi:10.1016/j.jhep.2010.03.005.
    • Maini MK, Schurich A (2010). The molecular basis of the failed immune response in chronic HBV: therapeutic implications.. J Hepatol, 52(4), 616 - 619. doi:10.1016/j.jhep.2009.12.017
    • Bertoletti A, Maini MK, Ferrari C (2010). The host-pathogen interaction during HBV infection: immunological controversies. ANTIVIR THER, 15, 15 - 24. doi:10.3851/IMP1620
    • Peppa D, Micco L, Javaid A, Kennedy PT, Schurich A, Dunn C, Pallant C, Ellis G, Khanna P, Dusheiko G, Gilson RJ, Maini MK (2010). Blockade of immunosuppressive cytokines restores NK cell antiviral function in chronic hepatitis B virus infection.. PLoS Pathog, 6(12), e1001227 - . doi:10.1371/journal.ppat.1001227

    2009

    • Dunn C, Peppa D, Khanna P, Nebbia G, Jones M, Brendish N, Lascar RM, Brown D, Gilson RJ, Tedder RJ, Dusheiko GM, Jacobs M, Klenerman P, Maini MK (2009). Temporal analysis of early immune responses in patients with acute hepatitis B virus infection.. Gastroenterology, 137(4), 1289 - 1300. doi:10.1053/j.gastro.2009.06.054

    2008

    • Lopes AR, Kellam P, Das A, Dunn C, Kwan A, Turner J, Peppa D, Gilson RJ, Gehring A, Bertoletti A, Maini MK (2008). Bim-mediated deletion of antigen-specific CD8 T cells in patients unable to control HBV infection. Journal of Clinical Investigation, 118(5), 1835 - 1845. doi:10.1172/JCI33402
    • Das A, Hoare M, Davies N, Lopes AR, Dunn C, Kennedy TF, Alexander G, Finney H, Lawson A, Plunkett FJ, Akbar AN, Bertoletti A, Maini MK (2008). Functional Skewing of the global CD8 T cell population in chronic hepatitis B virus infection. Journal of Experimental Medicine, 205, 2111 - 2124.

    2007

    • Dunn C, Brunetto M, Reynolds G, Christophides T, Kennedy PT, Lampertico P, Das A, Lopes AR, Borrow P, Williams K, Humphreys E, Afford S, Adams DH, Bertoletti A, Maini MK (2007). Cytokines induced during chronic hepatitis B virus infection promote a pathway for NK cell-mediated liver damage. Journal of Experimental Medicine, 204(3), 667 - 680. doi:10.1084/jem.20061287
    • Gehring AJ, Sun D, Kennedy PT, Nolte-'t HE, Lim SG, Wasser S, Selden C, Maini MK, Davis DM, Nassal M, Bertoletti A (2007). The level of viral antigen presented by hepatocytes influences CD8 T-cell function. J Virol., 81(6), 2940 - 2949.

    2006

    • Kennedy PTF, Urbani S, Moses RA, Amadei B, Fisicaro P, Lloyd J, Maini MK, Dusheiko G, Ferrari C, Bertoletti A (2006). The Influence of T Cell Cross-Reactivity on HCVPeptide Specific Human T Cell Response.. Hepatology, 43, 602 - 611.
    • Turnbull EL, Lopes AR, Jones NA, Cornforth D, Newton P, Aldam D, Pellegrino P, Turner J, Williams I, Wilson CM, Goepfert PA, Maini MK, Borrow P (2006). HIV-1 epitope-specific CD8+ T cell responses strongly associated with delayed disease progression cross-recognize epitope variants efficiently. The Journal of Immunology, 176(10), 6130 - 6146.

    2005

    • Maini MK, Bertoletti A (2005). The effects of pathogens on the immune system: viral hepatitis.. In Frelinger JA (Ed.), Immunodominance: The choice of the immune system (pp. - ). : Wiley-VCH.
    • Lascar RM, Lopes AR, Gilson RJ, Dunn C, Johnstone R, Copas A, Reignat S, Webster G, Bertoletti A, Maini MK (2005). Effect of HIV infection and antiretroviral therapy on hepatitis B virus (HBV)-specific T cell responses in patients who have resolved HBV infection. J INFECT DIS, 191(7), 1169 - 1179.
    • Franzese O, Kennedy PT, Gehring AJ, Gotto J, Williams R, Maini MK, Bertoletti A (2005). Modulation of the CD8+-T-cell response by CD4+ CD25+ regulatory T cells in patients with hepatitis B virus infection.. J Virol, 79(6), 3322 - 3328. doi:10.1128/JVI.79.6.3322-3328.2005

    2003

    • Bertoletti A, Maini M, Williams R (2003). Role of hepatitis B virus specific cytotoxic T cells in liver damage and viral control. Antiviral Research, 60(2), 61 - 66.
    • Lopes AR, Jaye A, Dorrell L, Sabally S, Alabi A, Jones NA, Flower DR, De Groot A, Newton P, Lascar RM, Williams I, Whittle H, Bertoletti A, Borrow P, Maini MK (2003). Greater CD8+ TCR heterogeneity and functional flexibility in HIV-2 compared to HIV-1 infection. The Journal of Immunology, 171(1), 307 - 316.
    • Lascar RM, Gilson RJC, Lopes AR, Bertoletti A, Maini MK (2003). Reconstitution of hepatitis B virus (HBV)-specific T cell responses with treatment of human immunodeficiency virus/HBV coinfection. The Journal of Infectious Diseases, 188(12), 1815 - 1819. doi:10.1086/379896

    2002

    • Reignat S, Webster GJ, Brown D, Ogg GS, King A, Seneviratne SL, Dusheiko G, Williams R, Maini MK, Bertoletti A (2002). Escaping high viral load exhaustion: CD8 cells with altered tetramer binding in chronic hepatitis B virus infection. Journal of Experimental Medicine, 195(9), 1089 - 1101. doi:10.1084/jem.20011723
    • Maini MK, Bertoletti A (2002). Cytokines in viral hepatitis. In Kobt M, Calandra T (Ed.), Cytokines and chemokines in infectious diseases (pp. 355 - 375). : Humana Press.

    2000

    • Bertoletti A, Maini MK (2000). Protection or damage: a dual role for the virus-specific cytotoxic T lymphocyte response in hepatitis B and C infection?. Curr Opin Microbiol, 3(4), 387 - 392.
    • Webster GJ, Reignat S, Maini MK, Whalley SA, Ogg GS, King A, Brown D, Amlot PL, Williams R, Vergani D, Dusheiko GM, Bertoletti A (2000). Incubation phase of acute hepatitis B in man: dynamic of cellular immune mechanisms. Hepatology, 32(5), 1117 - 1124.
    • Maini MK, Bertoletti A (2000). How can the cellular immune response control hepatitis B virus replication?. Journal of Viral Hepatitis, 7(5), 321 - 326.
    • Beverley PCL, Maini MK (2000). Differences in the regulation of CD4 and CD8 T-cell clones during immune responses.
    • Maini MK, Gudgeon N, Wedderburn LR, Rickinson AB, Beverley PC (2000). Clonal expansions in acute EBV infection are detectable in the CD8 and not the CD4 subset and persist with a variable CD45 phenotype. The Journal of Immunology, 165(10), 5729 - 5737.
    • Bertoletti A, Maini MK (2000). Protection or damage: a dual role for the virus-specific cytotoxic T lymphocyte response in hepatitis B and C infection?. Current Opinion in Immunology, 12(4), 403 - 408.
    • Soares MVD, Maini MK, Beverley PCL, Salmon M, Akbar AN (2000). Regulation of apoptosis and replicative senescence in CD8+ T cells from patients with viral infections. Biochemical Society Transactions, 28(Part 2), 255 - 258.
    • Maini MK, Boni C, Lee CK, Larrubia JR, Reignat S, Ogg GS, King AS, Herberg J, Gilson R, Alisa A, Williams R, Vergani D, Naoumov NV, Ferrari C, Bertoletti A (2000). The role of virus-specific CD8(+) cells in liver damage and viral control during persistent hepatitis B virus infection. Journal of Experimental Medicine, 191(8), 1269 - 1280. doi:10.1084/jem.191.8.1269
    • Beverley PC, Maini MK (2000). Differences in the regulation of CD4 and CD8 T-cell clones during immune responses. Philosophical Transactions of the Royal Society B: Biological Sciences, 355(1395), 401 - 406. doi:10.1098/rstb.2000.0580
    • Maini MK, Reignat S, Boni C, Ogg GS, King AS, Malacarne F, Webster GJM, Bertoletti A (2000). T cell receptor usage of virus-specific CD8 cells and recognition of viral mutations during acute and persistent hepatitis B virus infection. European Journal of Immunology, 30(11), 3067 - 3078.

    1999

    • Maini MK, Soares MVD, Zilch CF, Akbar AN, Beverley PCL (1999). Virus-induced CD8(+) T cell clonal expansion is associated with telomerase up-regulation and telomere length preservation: A mechanism for rescue from replicative senescence. J IMMUNOL, 162(8), 4521 - 4526.
    • Maini MK, Boni C, Ogg GS, King AS, Reignat S, Lee CK, Larrubia JR, Webster GJ, McMichael AJ, Ferrari C, Williams R, Vergani D, Bertoletti A (1999). Direct ex vivo analysis of hepatitis B virus-specific CD8(+) T cells associated with the control of infection.. Gastroenterology, 117(6), 1386 - 1396.
    • Wedderburn LR, Maini MK, Patel A, Beverley PCL, Woo P (1999). Molecular fingerprinting reveals non-overlapping T cell oligoclonality between an inflamed site and peripheral blood. INT IMMUNOL, 11(4), 535 - 543.
    • Maini MK, Casorati G, Dellabona P, Wack A, Beverley PCL (1999). T-cell clonality in immune responses. IMMUNOL TODAY, 20(6), 262 - 266.

    1998

    • Maini M (1998). Clonal dynamics and turnover in T cell memory.
    • Maini MK, Wedderburn LR, Hall FC, Wack A, Casorati G, Beverley PCL (1998). Comparison of two techniques for the molecular tracking of specific T-cell responses; CD4(+) human T-cell clones persist in a stable hierarchy but at a lower frequency than clones in the CD8(+) population. IMMUNOLOGY, 94(4), 529 - 535.
    • Soares MVD, Borthwick NJ, Maini MK, Janossy G, Salmon M, Akbar AN (1998). Interleukin-7 dependent extrarhythmic expansion of CD45RA + T cells enables preservation of a naive repertoire. The Journal of Immunology, 161, 5909 - 5917.

    1996

    • Maini NK, Gilson RJ, Chavda N, Gill S, Fakoya A, Ross EJ, Phillips AN, Weller IVD (1996). Reference ranges and sources of variability of CD4 counts in HIV-seronegative women and men. Genitourinary Medicine, 72(1), 27 - 31. doi:10.1136/sti.72.1.27

    1994

    • Robinson P, Zakrzewska JM, Maini M, Williamson D, Croucher R (1994). Dental visiting behaviour and experiences of men with HIV. British Dental Journal, 176(5), 175 - 179.

    1992

    • Maini M, French P, Prince M, Bingham JS (1992). Urethritis due to Neisseria meningitidis in a London genitourinary medicine clinic population. International Journal of STD and AIDS, 3, 423 - 425.

    1991

    • Davidson RN, Croft SL, Scott A, Maini M, Moody AH, Bryceson AD (1991). Liposomal amphotericin B in drug-resistant visceral leishmaniasis. The Lancet, 337, 1061 - 1062.