Dr Heather Long

Heather Long.School of Cancer Sciences Day 1 110311.

Dr Heather Long’s research is focused on developing immune T cell-based therapies for the treatment of EBV-associated and non-virus associated lymphomas.
Position:

Kay Kendall Research Fellow, School of Cancer Sciences, College of Medical Sciences and Dentistry, University of Birmingham.

Email: h.m.long@bham.ac.uk

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Background and Research focus

Heather has a long-standing interest in studying the CD4+ T cell response to Epstein-Barr
virus (EBV) and virus-related B cell lymphomas. The presentation of viral antigens by MHC class II positive malignant B cells makes them a highly attractive target for immunotherapy with CD4+ CTLs. In recent times, Heather has showed that EBV-specific CD4+ T cells can directly recognise and eliminate virus-infected cells. These important observations may explain the increased clinical efficacy of adoptively transferred EBV-specific T cells containing increased proportions of CD4+ T cells to treat EBV-associated post-transplant lymphoproliferative disease. Current projects in Heather’s group include probing the identity/functional characteristics of the CD4+ T cells present in adoptively transferred therapeutic CTLs and following their kinetics in vivo. These studies may lead to the identification of virus-specific CD4+ T cells with the greatest potential to target EBV-associated malignancies. Heather is also interested in B cell lymphomas that are not associated with viral infection. With this in mind, Heather has recently highlighted that EBV transformation can lead to the up-regulation of not only viral antigens, but also cellular antigens that serve as targets for CD4+ T cells. Crucially, these cellular targets are also expressed in other non-virus-associated lymphomas, and may provide novel therapeutic targets for lymphoma. Therefore, her group are presently exploring the identity of these new target antigens and evaluating their potential as therapeutic target antigens for immune therapy of wider non-virus related lymphoma.

Expertise

EBV-associated malignancy; CD4 T cells; B-cell Lymphoma; tumour immunotherapy; tumour immunology; viral oncology.

Other activities

Heather was recently awarded a Kay Kendall Leukaemia Fund Travel Fellowship to facilitate her own independent research. This included a working visit to the Ludwig Institute in Brussels. Heather has also published a number of peer reviewed research papers on the immune response to EBV. She also serves as an invited reviewer for several journals including Immunology and Journal of General Virology. In addition to her research, Heather has made significant contributions to teaching at the University of Birmingham, particularly on MSc and MBChB courses.  She is also co-lead in the new Step into Research initiative set up in the School of Cancer Sciences. The main aims of this scheme are to allow undergraduates who are contemplating a future career in research to undertake short projects during the summer vacation before their final year of study, and to aid recruitment of talented students onto future PhD programmes. Finally, she sits on the Cancer Immunotherapy and Immunology Centre Advisory Board.

Publications

Rickinson AB, Long HM, Palendira U, Münz C, Hislop AD. (2014) Cellular immune controls over Epstein-Barr virus infection: new lessons from the clinic and the laboratory. Trends Immunol. Apr;35(4):159-69.

Long HM, Chagoury OL, Leese AM, Ryan GB, James E, Morton LT, Abbott RJM, Sabbah S, Kwok W and Rickinson AB. (2013). MHC II Tetramers visualising human CD4+ T cell responses to Epstein-Barr virus infection: atypical kinetics of the EBNA1 response. J Exp Med. May 6;210(5):933-49.

Shetty S, Bruns T, Weston CJ, Stamataki Z, Oo YH, Long HM, Reynolds GM, Pratt G, Moss P, Jalkanen S, Hubscher SG, Lalor PF, Adams DH. Recruitment mechanisms of primary and malignant B cells to the human liver. Hepatology. 2012 Oct;56(4):1521-31.

Long, HM., Leese, AM., Chagoury, OL., Connerty, SR., Quarcoopome, J., Quinn, LL., Shannon-Lowe, C., Rickinson, AB. (2011) Cytotoxic CD4+ T cell responses to Epstein-Barr virus contrast with CD8 responses in breadth of lytic cycle antigen choice and in lytic cycle recognition. J Immunol.187:92-101.

Zuo J, Thomas WA, Haigh TA, Fitzsimmons L, Long HM, Hislop AD, Taylor GS, Rowe M. (2011) Epstein-Barr Virus Evades CD4 T Cell Responses in Lytic Cycle through BZLF1-mediated Downregulation of CD74 and the Cooperation of vBcl-2. PLoS Pathog.7(12):e1002455.

Long, HM., Taylor, GS., Rickinson, AB. (2011) Immune defence against EBV and EBV-associated disease. Curr Opin Immunol. 23(2):258-64. 23(2):258-64.

Fox, CP., Haigh, TA., Taylor, GS., Lee, SP., Long, HM., Shannon-Lowe, C., O’Connor, S., Bollard, CM., Iqbal, J., Chan, WC., Rickinson, AB., Bell, AI., Rowe, M. (2010) A novel latent membrane 2 transcript expressed in Epstein-Barr virus-positive NK and T cell lymphoproliferative disease encodes a target for cellular immunotherapy. Blood. 116(19):3695-704.

Long, H.M., G. Parsonage, C.P. Fox and S.P. Lee. 2010. Immunotherapy for Epstein-Barr virus-associated malignancies. Drug News Perspect. 23. 221-228.

Long HM, Zuo J, Leese AM, Gudgeon NH, Jia H, Taylor GS, Rickinson AB. CD4+ T-cell clones recognizing human lymphoma-associated antigens: generation by in vitro stimulation with autologous Epstein-Barr virus-transformed B cells. Blood.  2009 Jul 23;114(4):807-15.

Mackay, LK., Long, HM., Brooks, JM., Taylor, GS., Leung, CS., Chen, A., Wang, F., Rickinson, AB. (2009) T cell detection of a B-cell tropic virus infection: newly-synthesised versus mature viral proteins as antigen sources for CD4 and CD8 epitope display. PLoS Pathog. 5(12):e1000699.