Job Title: Senior Lecturer in Immunology
Email Address: RAicheler@cardiffmet.ac.uk
Phone Number: + 44 (0) 29 2041 5559
Room Number: D2.10
Teaching
I teach Immunology and Virology on the Biomedical Sciences and Health Care Science BSc degree courses as well as on the MSc Biomedical Science degree course. I also teach pathophysiology of disease to the Health Exercise and Nutrition degree and the Complimentary Healthcare Science degree.
I teach on the following modules:
Undergraduate
- Infection and Immunity A
- APS5013 Principles and Practice of Cellular Sciences
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SBM5001 Pathophysiology of Disease – (Module Lead)
- APS6008 Contemporary Topics in Biomedical Science
Postgraduate
- MBS7021 Analytical and Diagnostic Techniques
- MBS7008 Medical Microbiology
- MBS7009 Advanced Topics in Medical Microbiology
- MBS7003 Advanced Topics in Immunohaematology
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MBS7013 Immunology – (Module Lead)
Research
My research passion lies with understanding what regulates the function of Natural Killer (NK) cells. NK cells constitute a heterogeneous population of innate lymphocytes that exhibit an extraordinary capacity to kill tumour cells and control certain viral infections. NK cells are able to act independently of specific antigen recognition making them a key constituent of the innate immune response. Their function is regulated by integrating a combination of activating and inhibitory signals received from ligands on their targets and my research questions focus on understanding how these signals regulate NK cell function.
My research projects include: (1) Modulation of the NK Response by Human Cytomegalovirus
Human Cytomegalovirus (HCMV) is a ubiquitous β-herpes virus that establishes a persistent lifelong infection in the host. HCMV is a major cause of morbidity and mortality in immunocompromised individuals such as those suffering from HIV/AIDs or undergoing immunosuppressive drug therapies. The virus poses a significant risk to unborn foetuses and is a major cause of congenital malformation. NK cells play a crucial role in controlling cytomegalovirus infections such that individuals who are deficient in these cells often suffer from overt HCMV disease. My research focusses on identifying novel mechanisms encoded by the virus that enable it to modulate the NK cell response. This research gives us not only a better understanding of the interaction between NK cells and HCMV infected cells, but also has important implications for understanding the general mechanisms regulating NK cell function.
HCMV UL141 alters the distribution of CD155, an activator of NK cell function. In the top panel CD155 (in red) is found at the cell surface. In the bottom panel HCMV UL141 (in green) causes CD155 (in red) to be redistributed from the cell surface to the intracellular compartment called the Endoplasmic Reticulum where the two proteins co-localise (in merge shown in yellow). This prevents NK cells from binding to CD155 and leads to inhibition of NK cell degranulation in response to HCMV infected cells.
(2) Virotherapeutics and NK Cell function NK cells have the ability to recognise and kill diverse types of tumour cells thus providing an attractive avenue for novel immunotherapeutic treatment of a range of cancers. However, in the clinic NK cell immunotherapy has been met with limited success and new approaches for harnessing the ability of NK cells to kill cancer cells are needed.
Oncolytic viruses, those that can selectively infect and kill cancer cells, offer a unique opportunity not only to directly kill cancer cells but to boost the immune response to eradicate tumours. Working in collaboration with Dr Alan Parker at Cardiff University, we are developing a novel oncolytic adenovirus vector that is capable of infecting primary ovarian cancer cells. This vector has the capacity to encode a transgene that when expressed can modulate the NK cell response. My research focusses on phenotyping and functionally profiling NK cells in the ascites of patients with ovarian carcinoma to better enable us to design a vector that can boost the natural ability of NK cells to recognise and lyse ovarian cancer cells in patients.
Publications
- Fielding CA, Weekes MP, Nobre LV, Ruckova E, Wilkie GS, Paulo JA, Chang C, Suárez NM, Davies JA, Antrobus R, Stanton RJ,
Aicheler RJ, Nichols H, Vojtesek B, Trowsdale J, Davison AJ, Gygi SP, Tomasec P, Lehner PJ, Wilkinson GW. (2017) Control of immune ligands by members of a cytomegalovirus gene expansion suppresses natural killer cell activation. Elife. 10;6. pii: e22206. DOI: 10.7554/eLife.22206.
- Wilkinson, G.W., Davison, A.J., Tomasec, P., Fielding, C.A.,
Aicheler, R., Murrell, I., Seirafian, S., Wang, E.C., Weekes, M., Lehner, P.J., Wilkie, G.S., Stanton, R.J. (2015) Human Cytomegalovirus: taking the strain. Med Microbiol Immunol. 204(3): 273-84. Review DOI: 10.1007/s00430-015-0411-4
- Stanton, R.J., Prod'homme, V., Purbhoo, M.A., Moore, M.,
Aicheler, R.J., Heinzmann, M., Bailer, S.M., Haas, J., Antrobus, R., Weekes, M.P., Lehner, P.J., Vojtesek, B., Miners, K.L., Man, S., Wilkie, G.S., Davison, A.J., Wang, E.C., Tomasec, P., and Wilkinson, G.W. (2014) HCMV pUL135 remodels the actin cytoskeleton to impair immune recognition of infected cells. Cell Host Microbe. 13;16(2):201-14. DOI: 10.1016/j.chom.2014.07.005
- Weekes, M.P., Tomasec, P., Huttlin, E.L., Fielding, C.A., Nusinow, D., Stanton, R.J., Wang, E.C.,
Aicheler, R., Murrell, I., Wilkinson, G.W., Lehner, P.J., Gygi, S.P. (2014) Quantitative temporal viromics: an approach to investigate host-pathogen interaction. Cell. 5;157(6):1460-72. DOI: 10.1016/j.cell.2014.04.028
- Fielding, C.A.,
Aicheler, R., Stanton, R.J., Wang E.C., Han, S., Seirafian, S., Davies, J., McSharry, B,P., Weekes, M.P., Antrobus, P.R., Prod'homme, V., Blanchet, F.P., Sugrue, D., Cuff, S., Roberts, D., Davison, A.J., Lehner, P.J., Wilkinson, G.W., and Tomasec, P. (2014) Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation. PLoS Pathog. 1:10(5) DOI: 10.1371/journal.ppat.1004058
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Aicheler, R.J., Wang, E.C.Y., Tomasec, P., Wilkinson, G.W and Stanton, R.J. (2013) Potential for Natural Killer Cell-Mediated Antibody-Dependent Cellular Cytotoxicity for Control of HumanCytomegalovirus. Antibodies 2:(4):617-35 Review DOI:10.3390/antib2040617
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Aicheler; R*., Wendell, S*., Tomasec; P*., Loewendorf, A., Nemcovicova, I., Wang, E.C., Stanton, R., Macauley, M., Norris, N., Willen, L., Ruckova, E., Schneider, P., Hahn, G., Zajonc, D., Ware, C.F., Wilkinson, G.W., and Benedict, C. (2013). Human cytomegalovirus UL141 targets the TRAIL death receptors to inhibit host innate defenses. Cell Host and Microbe. * These authors contributed equally. Cell Host Microbe 13(3):324-35 DOI: 10.1016/j.chom.2013.02.003
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Aicheler, R., and Stanton, R., (2013). Functional NK Cell Cytotoxicity Assays Against Virus Infected Cells. Methods Mol Biol. 1064:275-87. DOI: 10.1007/978-1-62703-601-6_20
Book Chapters
- Wilkinson, G.W., Aicheler, R., and Wang, E.C.Y. (2013). Chapter II.8: Natural Killer Cells and Human Cytomegalovirus. Cytomegaloviruses from Molecular Pathogenesis to Intervention. Caister Press. 2013
Presentations
National and International Oral Presentations
- 2016 British Natural Kill Cell Symposium
- 2016 British Microbiological Society
- 2013 British Human Cytomegalovirus Conference
- 2011 British Human Cytomegalovirus Conference
- 2008 British Society for Immunology Annual Congress
- 2008 11th Meeting of the Society for Natural Immunity
- 2008 International Herpesvirus Workshop
- 2008 Workshop on Innate anti-viral Immunity and Virus Evasion
National and International Poster Presentations
- 2013 International Congress of Immunology
- 2008 International Herpesvirus Workshop
- 2008 International Herpesvirus Workshop
- 2004 British Society of Immunology
External Links
- Associate of the HEA
- Member of the British Society of Immunology
- Secretary of the British Society of Immunology, South Wales
- Honorary Research Fellow, Cardiff University
Professional Networking
