Dr Wioleta Zelek
(hi/ei)
Race Against Dementia and Alzheimer's Research UK Fellow, UK-DRI Arweinydd sy'n Dod i'r Amlwg
- Ar gael fel goruchwyliwr ôl-raddedig
Trosolwyg
Mae gen i ffocws ymchwil cryf ar y system ategu, ei bioleg, rolau mewn clefydau ac wrth drin y system ar gyfer therapi. Fy niddordeb penodol yw llwybr terfynell y system ategu sy'n cynhyrchu'r moleciwlau llidiol iawn C5a a'r cymhleth ymosod bilen (MAC). Fy ffocws presennol yw datblygu asiantau gwrth-MAC sy'n gallu atal llid, ac ymchwilio i fioleg sylfaenol strwythur a swyddogaeth MAC i nodi targedau y gellir eu cyffur.
https://www.raceagainstdementia.com/rad-fellows/dr-wioleta-zelek/
https://ukdri.ac.uk/team/wioleta-zelek
Cyhoeddiad
2024
- 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)
- 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. 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)
- Daskoulidou, N., Carpanini, S., Zelek, W. and Morgan, B. P. 2024. Involvement of complement in Alzheimer's Disease: From genetics through pathology to therapeutic strategies. In: Ellenbroek, B. A. et al. eds. Current Topics in Behavioral Neurosciences. Springer, Berlin, Heidelberg, pp. 1-22., (10.1007/7854_2024_524)
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
- 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)
- 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. 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)
Book sections
- Daskoulidou, N., Carpanini, S., Zelek, W. and Morgan, B. P. 2024. Involvement of complement in Alzheimer's Disease: From genetics through pathology to therapeutic strategies. In: Ellenbroek, B. A. et al. eds. Current Topics in Behavioral Neurosciences. Springer, Berlin, Heidelberg, pp. 1-22., (10.1007/7854_2024_524)
Thesis
- Zelek, W. 2019. Targeting the terminal pathway in complement – driven disease.. PhD Thesis, Cardiff University.
Ymchwil
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."
Bywgraffiad
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.
Meysydd goruchwyliaeth
Goruchwyliaeth gyfredol
Rebekah Cooke
Tiwtor Graddedig
Aurora Veteleanu
Myfyriwr ymchwil
Contact Details
+44 29206 87860
Adeilad Henry Wellcome ar gyfer Ymchwil Biofeddygol, Llawr 4ydd Llawr, Ystafell 4F10, Ysbyty Athrofaol Cymru, Parc y Mynydd Bychan, Caerdydd, CF14 4XN