Dr Wioleta Zelek
(she/her)
Race Against Dementia and Alzheimer's Research UK Fellow, UK-DRI Emerging Leader
- ZelekW@cardiff.ac.uk
- +44 29206 87860
- Henry Wellcome Building for Biomedical Research, Floor 4th Floor, Room 4F10, University Hospital of Wales, Heath Park, Cardiff, CF14 4XN
- Available for postgraduate supervision
Overview
I have a strong research focus on the complement system, its biology, roles in disease and in manipulating the system for therapy. My specific interest is in the terminal pathway of the complement system that generates the highly pro-inflammatory molecules C5a and the membrane attack complex (MAC). My current focus is on the development of anti-MAC agents capable of inhibiting inflammation, and investigating the basic biology of MAC structure and function to identify druggable targets.
https://www.raceagainstdementia.com/rad-fellows/dr-wioleta-zelek/
https://ukdri.ac.uk/team/wioleta-zelek
Publication
2024
- Kharnaf, M. et al. 2024. Factor XII promotes the thromboinflammatory response in a rat model of veno-arterial extracorporeal membrane oxygenation.. The Journal of Thoracic and Cardiovascular Surgery 168(2), pp. E37-E53. (10.1016/j.jtcvs.2023.08.045)
- Zelek, W. M., Bevan, R. J., Nimmo, J., Dewilde, M., De Strooper, B. and Morgan, B. P. 2024. Brain-penetrant complement inhibition mitigates neurodegeneration in an Alzheimer's disease mouse model. Brain (10.1093/brain/awae278)
- Zelek, W. M. 2024. Is Long COVID a complement dysregulation disease?. Clinical Chemistry (10.1093/clinchem/hvae088)
- Zelek, W. M., Bevan, R. J. and Morgan, B. P. 2024. Targeting terminal pathway reduces brain complement activation, amyloid load and synapse loss, and improves cognition in a mouse model of dementia. Brain, Behavior, and Immunity 118, pp. 355-363. (10.1016/j.bbi.2024.03.017)
- Nimmo, J., Byrne, R., Daskoulidou, N., Watkins, L., Carpanini, S., Zelek, W. and Morgan, B. 2024. The complement system in neurodegenerative diseases. Clinical Science 138(6), pp. 387-412. (10.1042/cs20230513)
- Baillie, K. et al. 2024. Complement dysregulation is a prevalent and therapeutically amenable feature of long COVID. Med 5(3), pp. 239-253. (10.1016/j.medj.2024.01.011)
- Kodosaki, E. et al. 2024. Combination protein biomarkers predict multiple sclerosis diagnosis and outcomes. Journal of Neuroinflammation 21(1), article number: 52. (10.1186/s12974-024-03036-4)
2023
- Kamegai, N. et al. 2023. Complement terminal pathway inhibition reduces peritoneal injuries in a rat peritonitis model. Clinical & Experimental Immunology 214(2), pp. 209-218. (10.1093/cei/uxad088)
- Veteleanu, A. et al. 2023. Alzheimer’s disease-associated complement gene variants influence plasma complement protein levels. Journal of Neuroinflammation 20(1), article number: 169. (10.1186/s12974-023-02850-6)
- Zelek, W. M. and Harrison, R. A. 2023. Complement and COVID-19: Three years on, what we know, what we don't know, and what we ought to know. Immunobiology 228(3), article number: 152393. (10.1016/j.imbio.2023.152393)
- Veteleanu, A. et al. 2023. Complement dysregulation and Alzheimer's disease in Down syndrome. Alzheimer's & Dementia: The Journal of the Alzheimer's Association 19(4), pp. 1383-1392. (10.1002/alz.12799)
- Goff, L. M. et al. 2023. Ethnic differences in complement system biomarkers and their association with metabolic health in men of Black African and White European ethnicity. Clinical & Experimental Immunology 212(1) (10.1093/cei/uxad011)
- Siggins, M. K. et al. 2023. Alternative pathway dysregulation in tissues drives sustained complement activation and predicts outcome across the disease course in COVID-19.. Immunology 168(3), pp. 473-492. (10.1111/imm.13585)
2022
- Lekova, E. et al. 2022. Discovery of functionally distinct anti-C7 monoclonal antibodies and stratification of anti-nicotinic AChR positive Myasthenia Gravis patients. Frontiers in Immunology 13, article number: 968206. (10.3389/fimmu.2022.968206)
- Zelek, W. M. and Morgan, B. P. 2022. Targeting complement in neurodegeneration: challenges, risks, and strategies. Trends in Pharmacological Sciences 43(8), pp. 615-628. (10.1016/j.tips.2022.02.006)
- Carpanini, S. M. et al. 2022. Terminal complement pathway activation drives synaptic Loss in Alzheimer’s disease models. Acta Neuropathologica Communications 10, article number: 99. (10.1186/s40478-022-01404-w)
- Fielding, C. A. et al. 2022. SARS-CoV-2 host-shutoff impacts innate NK cell functions, but antibody-dependent NK activity is strongly activated through non-spike antibodies. eLife 11 (10.7554/eLife.74489)
- Lewis, L. A. et al. 2022. Efficacy of an experimental gonococcal lipooligosaccharide mimitope vaccine requires terminal complement. The Journal of Infectious Diseases 225(10), pp. 1861–1864. (10.1093/infdis/jiab630)
- Kolka, C. M. et al. 2022. C5b-9 membrane attack complex formation and extracellular vesicle shedding in Barrett's esophagus and esophageal adenocarcinoma. Frontiers in Immunology 13, article number: 842023. (10.3389/fimmu.2022.842023)
- Scurr, M. et al. 2022. Whole blood-based measurement of SARS-CoV-2-specific T cells reveals asymptomatic infection and vaccine immunogenicity in healthy subjects and patients with solid organ cancers. Immunology 165(2), pp. 250-259. (10.1111/imm.13433)
2021
- Syrimi, E. et al. 2021. The immune landscape of SARS-CoV-2-associated multisystem inflammatory syndrome in children (MIS-C) from acute disease to recovery. iScience 24(11), article number: 103215. (10.1016/j.isci.2021.103215)
- Zelek, W. 2021. Measuring total classical pathway and activities of individual components of the mouse complement pathway. Bio-protocol 11(19), article number: e4175. (10.21769/BioProtoc.4175)
- Mc Mahon, O. et al. 2021. The rare C9 P167S risk variant for age-related macular degeneration increases polymerization of the terminal component of the complement cascade. Human Molecular Genetics 30(13), pp. 1188-1199. (10.1093/hmg/ddab086)
- Webster, J. A. et al. 2021. Development of EndoScreen chip, a microfluidic pre-endoscopy triage test for esophageal adenocarcinoma. Cancers 13(12), article number: 2865. (10.3390/cancers13122865)
- Moat, S. J. et al. 2021. Development of a high throughput SARS-CoV-2 antibody testing pathway using dried blood spot specimens. Annals of Clinical Biochemistry 58(2) (10.1177/0004563220981106)
- Murrell, I. et al. 2021. Temporal development and neutralising potential of antibodies against SARS-CoV-2 in hospitalised COVID-19 patients: An observational cohort study. PLoS ONE 16(1), article number: e0245382. (10.1371/journal.pone.0245382)
2020
- Buckland, M. S. et al. 2020. Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report. Nature Communications 11(1), article number: 6385. (10.1038/s41467-020-19761-2)
- Zelek, W. M. and Morgan, B. P. 2020. Monoclonal antibodies capable of inhibiting complement downstream of C5 in multiple species. Frontiers in Immunology 11(11), article number: 612402. (10.3389/fimmu.2020.612402)
- Zelek, W. M. et al. 2020. Cerebrospinal fluid complement system biomarkers in demyelinating disease. Multiple Sclerosis 26(14), pp. 1929-1937. (10.1177/1352458519887905)
- Zelek, W. M. et al. 2020. Complement inhibition with the C5 blocker LFG316 in severe COVID-19. American Journal of Respiratory and Critical Care Medicine 202(9), pp. 1304-1308. (10.1164/rccm.202007-2778LE)
- Zelek, W. M., Menzies, G. E., Brancale, A., Stockinger, B. and Morgan, B. P. 2020. Characterising the original anti-C5 function-blocking antibody, BB5.1, for species specificity, mode of action and interactions with C5. Immunology 161(2), pp. 103-113., article number: Volume161, Issue2 October 2020 Pages 103-113. (10.1111/imm.13228)
2019
- Zelek, W. 2019. Targeting the terminal pathway in complement – driven disease.. PhD Thesis, Cardiff University.
- Zelek, W. M., Xie, L., Morgan, B. P. and Harris, C. L. 2019. Compendium of current complement therapeutics. Molecular Immunology 114, pp. 341-352. (10.1016/j.molimm.2019.07.030)
- Zelek, W. M., Taylor, P. R. and Morgan, B. P. 2019. Development and characterisation of novel anti-C5 monoclonal antibodies capable of inhibiting complement in multiple species. Immunology 157(4), pp. 283-295. (10.1111/imm.13083)
- Zelek, W. M. et al. 2019. Measurement of soluble CD59 in CSF in demyelinating disease: Evidence for an intrathecal source of soluble CD59. Multiple Sclerosis 25(4), pp. 523-531. (10.1177/1352458518758927)
- Kopczynska, M. et al. 2019. Complement system biomarkers in first episode psychosis. Schizophrenia Research 204, pp. 16-22. (10.1016/j.schres.2017.12.012)
2018
- Zelek, W. M., Harris, C. L. and Morgan, B. P. 2018. Extracting the barbs from complement assays: Identification and optimisation of a safe substitute for traditional buffers. Immunobiology 223(12), pp. 744-749. (10.1016/j.imbio.2018.07.016)
- Zelek, W. M., Stott, M., Walters, D., Harris, C. L. and Morgan, B. P. 2018. Characterising a pH-switch anti-C5 antibody as a tool for human and mouse complement C5 purification and cross-species inhibition of classical and reactive lysis. Immunology 155(3), pp. 396-403. (10.1111/imm.12982)
- Kopczynska, M. et al. 2018. Complement system biomarkers in epilepsy. Seizure - European Journal of Epilepsy 60, pp. 1-7. (10.1016/j.seizure.2018.05.016)
- Boshra, H., Zelek, W. M., Hughes, T. R., Rodriguez de Cordoba, S. and Morgan, B. P. 2018. Absence of CD59 in guinea pigs: Analysis of the Cavia porcellus genome suggests the evolution of a CD59 pseudogene. Journal of Immunology 200(1), pp. 327-335. (10.4049/jimmunol.1701238)
Articles
- Kharnaf, M. et al. 2024. Factor XII promotes the thromboinflammatory response in a rat model of veno-arterial extracorporeal membrane oxygenation.. The Journal of Thoracic and Cardiovascular Surgery 168(2), pp. E37-E53. (10.1016/j.jtcvs.2023.08.045)
- Zelek, W. M., Bevan, R. J., Nimmo, J., Dewilde, M., De Strooper, B. and Morgan, B. P. 2024. Brain-penetrant complement inhibition mitigates neurodegeneration in an Alzheimer's disease mouse model. Brain (10.1093/brain/awae278)
- Zelek, W. M. 2024. Is Long COVID a complement dysregulation disease?. Clinical Chemistry (10.1093/clinchem/hvae088)
- Zelek, W. M., Bevan, R. J. and Morgan, B. P. 2024. Targeting terminal pathway reduces brain complement activation, amyloid load and synapse loss, and improves cognition in a mouse model of dementia. Brain, Behavior, and Immunity 118, pp. 355-363. (10.1016/j.bbi.2024.03.017)
- Nimmo, J., Byrne, R., Daskoulidou, N., Watkins, L., Carpanini, S., Zelek, W. and Morgan, B. 2024. The complement system in neurodegenerative diseases. Clinical Science 138(6), pp. 387-412. (10.1042/cs20230513)
- Baillie, K. et al. 2024. Complement dysregulation is a prevalent and therapeutically amenable feature of long COVID. Med 5(3), pp. 239-253. (10.1016/j.medj.2024.01.011)
- Kodosaki, E. et al. 2024. Combination protein biomarkers predict multiple sclerosis diagnosis and outcomes. Journal of Neuroinflammation 21(1), article number: 52. (10.1186/s12974-024-03036-4)
- Kamegai, N. et al. 2023. Complement terminal pathway inhibition reduces peritoneal injuries in a rat peritonitis model. Clinical & Experimental Immunology 214(2), pp. 209-218. (10.1093/cei/uxad088)
- Veteleanu, A. et al. 2023. Alzheimer’s disease-associated complement gene variants influence plasma complement protein levels. Journal of Neuroinflammation 20(1), article number: 169. (10.1186/s12974-023-02850-6)
- Zelek, W. M. and Harrison, R. A. 2023. Complement and COVID-19: Three years on, what we know, what we don't know, and what we ought to know. Immunobiology 228(3), article number: 152393. (10.1016/j.imbio.2023.152393)
- Veteleanu, A. et al. 2023. Complement dysregulation and Alzheimer's disease in Down syndrome. Alzheimer's & Dementia: The Journal of the Alzheimer's Association 19(4), pp. 1383-1392. (10.1002/alz.12799)
- Goff, L. M. et al. 2023. Ethnic differences in complement system biomarkers and their association with metabolic health in men of Black African and White European ethnicity. Clinical & Experimental Immunology 212(1) (10.1093/cei/uxad011)
- Siggins, M. K. et al. 2023. Alternative pathway dysregulation in tissues drives sustained complement activation and predicts outcome across the disease course in COVID-19.. Immunology 168(3), pp. 473-492. (10.1111/imm.13585)
- Lekova, E. et al. 2022. Discovery of functionally distinct anti-C7 monoclonal antibodies and stratification of anti-nicotinic AChR positive Myasthenia Gravis patients. Frontiers in Immunology 13, article number: 968206. (10.3389/fimmu.2022.968206)
- Zelek, W. M. and Morgan, B. P. 2022. Targeting complement in neurodegeneration: challenges, risks, and strategies. Trends in Pharmacological Sciences 43(8), pp. 615-628. (10.1016/j.tips.2022.02.006)
- Carpanini, S. M. et al. 2022. Terminal complement pathway activation drives synaptic Loss in Alzheimer’s disease models. Acta Neuropathologica Communications 10, article number: 99. (10.1186/s40478-022-01404-w)
- Fielding, C. A. et al. 2022. SARS-CoV-2 host-shutoff impacts innate NK cell functions, but antibody-dependent NK activity is strongly activated through non-spike antibodies. eLife 11 (10.7554/eLife.74489)
- Lewis, L. A. et al. 2022. Efficacy of an experimental gonococcal lipooligosaccharide mimitope vaccine requires terminal complement. The Journal of Infectious Diseases 225(10), pp. 1861–1864. (10.1093/infdis/jiab630)
- Kolka, C. M. et al. 2022. C5b-9 membrane attack complex formation and extracellular vesicle shedding in Barrett's esophagus and esophageal adenocarcinoma. Frontiers in Immunology 13, article number: 842023. (10.3389/fimmu.2022.842023)
- Scurr, M. et al. 2022. Whole blood-based measurement of SARS-CoV-2-specific T cells reveals asymptomatic infection and vaccine immunogenicity in healthy subjects and patients with solid organ cancers. Immunology 165(2), pp. 250-259. (10.1111/imm.13433)
- Syrimi, E. et al. 2021. The immune landscape of SARS-CoV-2-associated multisystem inflammatory syndrome in children (MIS-C) from acute disease to recovery. iScience 24(11), article number: 103215. (10.1016/j.isci.2021.103215)
- Zelek, W. 2021. Measuring total classical pathway and activities of individual components of the mouse complement pathway. Bio-protocol 11(19), article number: e4175. (10.21769/BioProtoc.4175)
- Mc Mahon, O. et al. 2021. The rare C9 P167S risk variant for age-related macular degeneration increases polymerization of the terminal component of the complement cascade. Human Molecular Genetics 30(13), pp. 1188-1199. (10.1093/hmg/ddab086)
- Webster, J. A. et al. 2021. Development of EndoScreen chip, a microfluidic pre-endoscopy triage test for esophageal adenocarcinoma. Cancers 13(12), article number: 2865. (10.3390/cancers13122865)
- Moat, S. J. et al. 2021. Development of a high throughput SARS-CoV-2 antibody testing pathway using dried blood spot specimens. Annals of Clinical Biochemistry 58(2) (10.1177/0004563220981106)
- Murrell, I. et al. 2021. Temporal development and neutralising potential of antibodies against SARS-CoV-2 in hospitalised COVID-19 patients: An observational cohort study. PLoS ONE 16(1), article number: e0245382. (10.1371/journal.pone.0245382)
- Buckland, M. S. et al. 2020. Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report. Nature Communications 11(1), article number: 6385. (10.1038/s41467-020-19761-2)
- Zelek, W. M. and Morgan, B. P. 2020. Monoclonal antibodies capable of inhibiting complement downstream of C5 in multiple species. Frontiers in Immunology 11(11), article number: 612402. (10.3389/fimmu.2020.612402)
- Zelek, W. M. et al. 2020. Cerebrospinal fluid complement system biomarkers in demyelinating disease. Multiple Sclerosis 26(14), pp. 1929-1937. (10.1177/1352458519887905)
- Zelek, W. M. et al. 2020. Complement inhibition with the C5 blocker LFG316 in severe COVID-19. American Journal of Respiratory and Critical Care Medicine 202(9), pp. 1304-1308. (10.1164/rccm.202007-2778LE)
- Zelek, W. M., Menzies, G. E., Brancale, A., Stockinger, B. and Morgan, B. P. 2020. Characterising the original anti-C5 function-blocking antibody, BB5.1, for species specificity, mode of action and interactions with C5. Immunology 161(2), pp. 103-113., article number: Volume161, Issue2 October 2020 Pages 103-113. (10.1111/imm.13228)
- Zelek, W. M., Xie, L., Morgan, B. P. and Harris, C. L. 2019. Compendium of current complement therapeutics. Molecular Immunology 114, pp. 341-352. (10.1016/j.molimm.2019.07.030)
- Zelek, W. M., Taylor, P. R. and Morgan, B. P. 2019. Development and characterisation of novel anti-C5 monoclonal antibodies capable of inhibiting complement in multiple species. Immunology 157(4), pp. 283-295. (10.1111/imm.13083)
- Zelek, W. M. et al. 2019. Measurement of soluble CD59 in CSF in demyelinating disease: Evidence for an intrathecal source of soluble CD59. Multiple Sclerosis 25(4), pp. 523-531. (10.1177/1352458518758927)
- Kopczynska, M. et al. 2019. Complement system biomarkers in first episode psychosis. Schizophrenia Research 204, pp. 16-22. (10.1016/j.schres.2017.12.012)
- Zelek, W. M., Harris, C. L. and Morgan, B. P. 2018. Extracting the barbs from complement assays: Identification and optimisation of a safe substitute for traditional buffers. Immunobiology 223(12), pp. 744-749. (10.1016/j.imbio.2018.07.016)
- Zelek, W. M., Stott, M., Walters, D., Harris, C. L. and Morgan, B. P. 2018. Characterising a pH-switch anti-C5 antibody as a tool for human and mouse complement C5 purification and cross-species inhibition of classical and reactive lysis. Immunology 155(3), pp. 396-403. (10.1111/imm.12982)
- Kopczynska, M. et al. 2018. Complement system biomarkers in epilepsy. Seizure - European Journal of Epilepsy 60, pp. 1-7. (10.1016/j.seizure.2018.05.016)
- Boshra, H., Zelek, W. M., Hughes, T. R., Rodriguez de Cordoba, S. and Morgan, B. P. 2018. Absence of CD59 in guinea pigs: Analysis of the Cavia porcellus genome suggests the evolution of a CD59 pseudogene. Journal of Immunology 200(1), pp. 327-335. (10.4049/jimmunol.1701238)
Thesis
- Zelek, W. 2019. Targeting the terminal pathway in complement – driven disease.. PhD Thesis, Cardiff University.
Research
My current focus is on generating anti-complement drugs for treatment of common inflammatory diseases such as multiple sclerosis, rheumatoid arthritis, kidneys disorders and dementia. During the pandemic I have re-focussed my work to address relevant issues; I supported a compassionate use study of anti-complement therapy in severe Covid-19, and developed assays for measurement of antibodies against the RBD domain of the SARS-Cov2 virus.
Grants and awards:
Jan 2022 – present: RAD/ARUK Fellow & UK-DRI Emerging Leader.
"Targeting novel anti-complement drugs to the brain for therapy of dementia."
https://ukdri.ac.uk/team/wioleta-zelek
Oct 2020 - Dec 2021: HCRW Fellow.
"Drug design for specific inhibition of the Membrane Attack Complex (MAC) in common inflammatory diseases."
Oct 2019 - Sep 2020: ISSF Fellow.
"Structure-function guided drug design for specific inhibition of the Membrane Attack Complex (MAC) in complement driven diseases."
Oct 2016 - Sep 2019: PhD Student.
"Targeting the terminal pathway in complement – driven disease."
Biography
Jan 2022 – present: Cardiff University, School of Medicine, Dementia Research Institute, Research Fellow. Race Against Dementia / Alzheimer's Research UK Fellowship Award & UK-DRI Emerging Leader status. "Targeting novel anti-complement drugs to the brain for therapy of dementia."
Oct 2020 – Dec 2021: Cardiff University, School of Medicine, Research Associate. Health and Care Research Fellowship Award. "Drug design for specific inhibition of the Membrane Attack Complex (MAC) in common inflammatory diseases."
Oct 2019 – Sep 2020: Cardiff University, School of Medicine, Research Associate. Institutional Strategic Support Fund via Wellcome Trust Consolidator Award. "Structure-function guided drug design for specific inhibition of the Membrane Attack Complex (MAC) in complement driven diseases."
Oct 2016 – Sep 2019: Cardiff University, School of Medicine, PhD Student. "Targeting the terminal pathway in complement - driven disease".
Jan 2015 – Sep 2016: Cardiff University, School of Medicine, Research Technician in Prof. B. Paul Morgan Group. "Complement biomarkers in autoimmune diseases."
Industry:
Jan 2013 – Dec 2014: RSR Limited, Cardiff. Scientist.
Jan 2007 – Dec 2013: BBI Group, Cardiff, Senior Scientist.
Dec 2006 – Dec 2007: Cardiff and Vale NHS Trust, Cardiff, Medical Laboratory Assistant.
Development of new products: ELISAs and LFAs; improvement of immunoassays performance and manufacturing processes, troubleshooting on products stability and sensitivity issues; data analysis of results obtained and generation of customer reports. Training and supervision of staff. Generation and approval of laboratory protocols; SOP's, EP's, QCP's, PP's. Accustomed to ISO 9001:2008, ISO13485:2003, FDA, GLP, GMP, PPE, SEQOHS, COSHH, H&S, GCP.
Supervisions
Current supervision
Rebekah Cooke
Graduate Tutor
Aurora Veteleanu
Research student