Dr Heather Long PhD

Heather Long

Institute of Immunology and Immunotherapy
Associate Professor

Contact details

Address
Institute of Immunology and Immunotherapy
CRC/Denis Howell Building
University of Birmingham
Edgbaston
Birmingham
B15 2TT

Dr Heather Long is an Associate Professor in the Institute of Immunology and Immunotherapy. She is the Institute Academic lead for Cancer Immunology.

Heather leads an active research team in the fields of viral and cancer immunology, with a long-term focus on understanding T cell control of viruses and virus-associated cancers.

Heather’s team have identified many novel T cell targets in viruses such as Epstein-Barr virus (EBV) and SARS-CoV-2, which have enabled the analysis of virus-specific T cell responses in a range of clinical samples.

Her recent work alongside a UK-wide Phase II clinical trial is applying this knowledge to EBV-driven lymphoma, where her team are identifying biomarkers for earlier detection and treatment.

Heather also leads a module on the MSc Immunology and Immunotherapy and contributes to teaching across a broad range of programmes within the Birmingham Medical School.

Dr Long's Google Scholar Profile

Qualifications

  • PhD in Cancer Studies, University of Birmingham, 2005
  • BSc (Hons) Biomedical Science, University of Hull, 2001

Biography

Heather Long was awarded a BSc (Hons) in Biomedical Science from the University of Hull in 2001. This included integrated training in haematology and blood transfusion at St James’ University Hospital, Leeds, where she qualified as a Biomedical Scientist with the Institute of Biomedical Science.

Heather subsequently joined the School of Cancer Sciences at the University of Birmingham, where she obtained her PhD in 2005. This was followed by Post-Doctoral research training in the laboratory of Prof Alan Rickinson, (2005-2012), which reinforced her interests in viral and cancer immunology.

In 2012, Heather was awarded a Kay Kendall Leukaemia Fund Fellowship to establish her own independent research, including a secondment at the Ludwig Institute for Cancer Research in Brussels.

Heather was awarded a lectureship in 2015 and was appointed as Associate Professor in 2021.

Teaching

  • MSc Immunology and Immunotherapy: Research Skills in Immunology, Autoimmunity Transplant and Tumour Immunology, Immunotherapy 1
  • MRes Cancer Sciences Cancer: Immunology and Immunotherapy module
  • BMedSc: Cancer and Stratified Medicine
  • MSci: Cell Communication in Health and Disease, Tumour Virology
  • MBChB: Cancer: Causes to Cures
  • ICS: Immunology and Liver Disease
  • Supervisor of PhD, MSc, MRes and BSc project students

Postgraduate supervision

Heather supervises students in the areas of viral and cancer immunology, including:

  • Understanding T cell control of Epstein-Barr virus (EBV)
  • The role of T cells in the control of EBV-associated lymphoma
  • Uncovering biomarkers of lymphoma
  • Lymphocyte infiltration into cancer

If you are interesting in studying any of these subject areas please contact Dr Heather Long directly, or for any general doctoral research enquiries, please email mds-gradschool@contacts.bham.ac.uk.

Research

Dr Heather Long is an Associate Professor with a research interest in viral and cancer immunology.

Understanding T cell control of Epstein-Barr virus

Epstein-Barr virus (EBV) is a common herpesvirus that is carried for life following infection. Although infection is usually asymptomatic, EBV is a clinically important virus. Primary infection is associated with infectious mononucleosis and long-term infection is associated with multiple sclerosis and with >200,000 new cancers each year. Our research focuses on understanding how T cells, in particular CD4+ T cells, target EBV and control long-term virus infection. We have discovered many regions of EBV that are targeted by T cells (epitopes). This enabled our lab to pioneer MHCII tetramer technology for single cell analysis of EBV-specific CD4+ T cells in a range of clinical samples. Our group studies the dynamic, functional and metabolic properties of EBV-specific T cells, and investigates the characteristics of resident memory T cells at the site of virus infection. Collectively, these studies improve our understanding of human T cell control of virus infection, which is essential to develop T cell-based treatments for EBV-associated disease.

Post-transplant lymphoproliferative disease (PTLD)

PTLD is a type of B cell lymphoma that develops in transplant patients because the immunosuppressive treatment they need also weakens the immune system’s defence against cancer. Many cases of PTLD are caused by EBV, which reactivates whilst the virus-specific T cell response is suppressed. PTLD is difficult to detect, therefore it is often diagnosed at an advanced stage when it is difficult to treat. Consequently, survival rates for PTLD patients are poor. Working alongside a UK-wide Phase II clinical trial, we have discovered immune signatures that are only present in those transplant patients that develop PTLD. We are currently validating these signatures in independent cohorts of PTLD patients, with a view to developing a predictive model for early detection of disease. In parallel, we are studying immunity inside PTLD tumours, to identify mechanisms of immune evasion within the tumour microenvironment that prevent T cell destruction. Together, we aim to identify biomarkers for disease detection and uncover novel potential therapeutic targets, thereby improving survival for patients with PTLD.

SARS-CoV-2

Upon the emergence of SARS-CoV-2, we sought to determine how virus-specific T cell immunity was impacted by ongoing viral mutations. We demonstrated that emerging variants of concern contained mutations in several CD4+ T cell epitopes that abolished T cell recognition. In collaboration with Cardiff University, using structural analysis, we described two novel mechanisms of T cell evasion by SARS-CoV-2. Our ongoing work is studying T cell immunity against regions of SARS-CoV-2 that are the most conserved among the family of existing human coronaviruses. Targeting these regions may provide pan-coronavirus protection against current and emerging viruses.

Collaborative research in Cancer Immunology

Our group is involved in the immunological aspects of several collaborative studies in cancer including childhood PTLD, EBV-associated T/NK cell disease and lung cancer. In addition, ongoing collaborative work with Dr Fedor Berditchevski has discovered a novel mechanism of B cell recruitment into breast cancer.

Other activities

  • Outreach charity work for Blood Cancer UK
  • Regular visits/science talks at local schools
  • Member of the Midlands Innovation Immunology Network
  • Project Grant Panel, Rosetrees Trust

Publications

Recent publications

Article

Jackson, HK, Long, HM, Yam‐Puc, JC, Palmulli, R, Haigh, TA, Gerber, PP, Lee, JS, Matheson, NJ, Young, L, Trowsdale, J, Lo, M, Taylor, GS, Thaventhiran, JE & Edgar, JR 2024, 'Bioengineered small extracellular vesicles deliver multiple SARS‐CoV‐2 antigenic fragments and drive a broad immunological response', Journal of Extracellular Vesicles, vol. 13, no. 2, e12412. https://doi.org/10.1002/jev2.12412

Offor, U, Hollis, P, Ognjanovic, M, Perry, G, Khushnood, A, Long, H, Gennery, A, Bacon, C, Simmonds, J, Reinhardt, Z & Bomken, S 2023, 'Immunology of THymectomy And childhood CArdiac transplant (ITHACA): protocol for a UK-wide prospective observational cohort study to identify immunological risk factors of post-transplant lymphoproliferative disease (PTLD) in thymectomised children', BMJ open, vol. 13, no. 10, e079582. https://doi.org/10.1136/bmjopen-2023-079582

Chen, Y, Mason, G, Scourfield, DO, Greenshields-Watson, A, Haigh, T, Sewell, A, Long, H, Gallimore, A, Rizkallah, P, MacLachlan, B & Godkin, A 2023, 'Structural definition of HLA class II-presented SARS-CoV-2 epitopes reveals a mechanism to escape pre-existing CD4+ T cell immunity', Cell Reports, vol. 42, no. 8, 112827. https://doi.org/10.1016/j.celrep.2023.112827

Molostvov, G, Gachechiladze, M, Shaaban, AM, Hayward, S, Dean, I, Dias, IHK, Badr, N, Danial, I, Mohammed, F, Novitskaya, V, Paniushkina, L, Speirs, V, Hanby, A, Nazarenko, I, Withers, DR, van Laere, S, Long, HM & Berditchevski, F 2023, 'Tspan6 stimulates the chemoattractive potential of breast cancer cells for B cells in an EV- and LXR-dependent manner', Cell Reports, vol. 42, no. 3, 112207. https://doi.org/10.1016/j.celrep.2023.112207

Tye, E, Jinks, E, Haigh, T, Kaul, B, Patel, P, Parry, H, Newby, M, Crispin, M, Kaur, N, Moss, P, Drennan, S, Taylor, G & Long, H 2022, 'Mutations in SARS-CoV-2 spike protein impair epitope-specific CD4+ T cell recognition', Nature Immunology, vol. 23, pp. 1726–1734. https://doi.org/10.1038/s41590-022-01351-7

Collins, P, Fox, CP, George, LC, Pearce, H, Ryan, GB, De Santo, C, Mussai, FJ, Lewis, D, Long, HM & Shannon-Lowe, CD 2021, 'Characterising EBV-associated lymphoproliferative diseases and the role of myeloid-derived suppressor cells', Blood, vol. 137, no. 2, pp. 203–215. https://doi.org/10.1182/blood.2020005611

Dowell, AC, Haigh, TA, Ryan, GB, Turner, JE, Long, HM & Taylor, GS 2021, 'Cytotoxic CD4+ T-cells specific for EBV capsid antigen BORF1 are maintained in long-term latently infected healthy donors', PLoS Pathogens, vol. 17, no. 12, e1010137. https://doi.org/10.1371/journal.ppat.1010137

Zuo, J, Dowell, AC, Pearce, H, Verma, K, Long, HM, Begum, J, Aiano, F, Amin-Chowdhury, Z, Hallis, B, Stapley, L, Borrow, R, Linley, E, Ahmad, S, Parker, B, Horsley, A, Amirthalingam, G, Brown, K, Ramsay, ME, Ladhani, S & Moss, P 2021, 'Robust SARS-CoV-2-specific T cell immunity is maintained at 6 months following primary infection', Nature Immunology, vol. 22, no. 5, pp. 620-626. https://doi.org/10.1038/s41590-021-00902-8

Sejic, N, George, L, Tierney, R, Chang, C, Kondrashova, O, MacKinnon, RN, Lan, P, Bell, A, Lessene, G, Long, H, Strasser, A, Shannon-Lowe, C & Kelly, GL 2020, 'BCL-XL inhibition by BH3-mimetic drugs induces apoptosis in models of Epstein-Barr virus-associated T/NK cell lymphoma', Blood Advances, vol. 4, no. 19, pp. 4775-4787. https://doi.org/10.1182/bloodadvances.2020002446

Hayward, S, Gachechiladze, M, Badr, N, Andrijes, R, Molostvov, G, Paniushkina, L, Sopikova, B, Slobodova, Z, Mgebrishvili, G, Sharma, N, Horimoto, Y, Burg, D, Robertson, G, Hanby, A, Hoar, F, Rea, D, Eckhardt, B, Ueno, N, Nazarenko, I, Long, H, van Laere, S, Shaaban, A & Berditchevski, F 2020, 'The CD151‐midkine pathway regulates the immune microenvironment in inflammatory breast cancer', Journal of Pathology, vol. 251, no. 1, pp. 63-73. https://doi.org/10.1002/path.5415

Munoz-Ruiz, M, Pujol-Autonell, I, Rhys, H, Long, H, Greco, M, Peakman, M, Tree, T, Hayday, A & Di Rosa, F 2020, 'Tracking immunodynamics by identification of S-G2/M-phase T cells in human peripheral blood', Journal of Autoimmunity, vol. 112, 102466. https://doi.org/10.1016/j.jaut.2020.102466

Parry, HM, Mirajkar, N, Cutmore, N, Zuo, J, Long, H, Kwok, M, Oldrieve, C, Hudson, C, Stankovic, T, Paneesha, S, Kelly, M, Begum, J, McSkeane, T, Pratt, G & Moss, P 2019, 'Long-Term Ibrutinib Therapy Reverses CD8+ T Cell Exhaustion in B Cell Chronic Lymphocytic Leukaemia', Frontiers in immunology, vol. 10, 2832. https://doi.org/10.3389/fimmu.2019.02832

Burns, DM, Ryan, GB, Harvey, CM, Nagy, E, Hughes, S, Murray, PG, Russell, NH, Fox, CP & Long, HM 2019, 'Non-uniform in vivo Expansion of Epstein-Barr Virus-Specific T-Cells Following Donor Lymphocyte Infusion for Post-transplant Lymphoproliferative Disease', Frontiers in immunology, vol. 10, no. OCT, 2489. https://doi.org/10.3389/fimmu.2019.02489

Letter

Bishton, M, Long, H, Dowell, A, Meckiff, B, Byrne, C & Fox, C 2019, 'Complete remission of immunochemotherapy-refractory monomorphic post-transplant lymphoproliferative disorder mediated by endogenous T-cell recovery', Leukemia and Lymphoma, vol. 60, no. 8, pp. 2075-2078. https://doi.org/10.1080/10428194.2019.1571203

Preprint

Zuo, J, Dowell, A, Pearce, H, Verma, K, Long, HM, Begum, J, Aiano, F, Amin-Chowdhury, Z, Hallis, B, Stapley, L, Borrow, R, Linley, E, Ahmad, S, Parker, B, Horsley, A, Amirthalingam, G, Brown, K, Ramsay, ME, Ladhani, S & Moss, P 2020 'Robust SARS-CoV-2-specific T-cell immunity is maintained at 6 months following primary infection' bioRxiv. https://doi.org/10.1101/2020.11.01.362319

View all publications in research portal