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 Web Page: Personal Web Page

Profile

Research Description

I am a clinician scientist who has worked for many years on T cell responses in chronic viral infections (EBV, HIV-1 and 2, HBV). Based in the Division of Infection and Immunity in the Windeyer Building, I now head a group of basic and clinical scientists all working on integrated aspects of the immunopathogenesis of chronic HBV infection. Our work uses samples from the viral hepatitis clinics that I do, and from our extensive clinical collaborations, to dissect out components of the immune response contributing to viral control versus liver damage. Key recent advances in our understanding of the T cell tolerance seen with HBV persistence have included the identification of Bim-mediated apoptosis as a mechanism of attrition of HBV-specific CD8, and the characterisation of defects attributable to the liver microenvironment that bias the effector function of CD8 cells. We are now investigating the degree to which the defective profile of these CD8 cells can be re-programmed by potent anti-viral therapy. Our work has also highlighted the potential of the large proportion of activated NK cells in the hepatic infiltrate to contribute to liver damage.
Our ultimate goal is to apply these insights to develop immunotherapeutic strategies that boost immune control of HBV with minimal liver damage, thereby allowing termination of long-term antiviral therapy and preventing the frequent outcomes of cirrhosis and hepatocellular carcinoma.

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 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 Anne Johnson; Prof Deenan Pillay; Prof Caroline Sabin; Dr Liz Jury; Prof Paul Kellam

External Collaborators

Publications

    2013

    • 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

    • 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
    • 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
    • Protzer U, Maini MK, Knolle PA (2012). Living in the liver: hepatic infections.. Nat Rev Immunol, 12(3), 201 - 213. doi:10.1038/nri3169
    • 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.
    • 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, 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
    • 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
    • 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
    • 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.

    2010

    • 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
    • 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
    • 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
    • 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.

    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

    • 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.
    • 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.

    2005

    • 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
    • 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.

    2003

    • 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
    • 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.
    • 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.

    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?. Current Opinion in Immunology, 12(4), 403 - 408.
    • Beverley PCL, Maini MK (2000). Differences in the regulation of CD4 and CD8 T-cell clones during immune responses.
    • 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.
    • 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.
    • 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.
    • 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, Bertoletti A (2000). How can the cellular immune response control hepatitis B virus replication?. Journal of Viral Hepatitis, 7(5), 321 - 326.
    • 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.

    1999

    • 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, 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, Casorati G, Dellabona P, Wack A, Beverley PCL (1999). T-cell clonality in immune responses. IMMUNOL TODAY, 20(6), 262 - 266.

    1998

    • 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.
    • 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.

    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.