Laboratory of Immunopathology

Research topics

The Immunopathology Laboratory originated from the Department of Experimental Therapy at the Institute of Immunology and Experimental Therapy of the Polish Academy of Sciences. Between 1997 and 2021, the Laboratory was headed by Prof. Irena Frydecka, MD, PhD, DSc.

Since 2021, the Laboratory has been headed by Edyta Pawlak, MD, PhD, DSc, Professor at the Polish Academy of Sciences.

One of the main research topics of the Immunopathology Laboratory, headed by Edyta Pawlak, MD, PhD, DSc, Prof. PAS, is the search for new therapeutic targets in cancer, systemic and organ autoimmune diseases, and mental disorders and illnesses.

The Laboratory’s research profile focuses on studies of the mechanisms of impaired immunity in malignant tumours (both solid and haematological), autoimmune diseases, and mental disorders and illnesses. The research covers a complex and intricate molecular network, in particular intercellular and intergenic (gene-gene) interactions, as well as gene-disease associations (GDA), in order to identify risk and prognostic factors for these disorders. The research is based on a multi-omic approach – the analysis of ‘omic’ data in combination with phenotypic and environmental data, including social determinants of health (SDOH), to detect and evaluate molecular ‘profiles’ associated with health and disease states, as well as transitions from health to disease or vice versa in malignant tumours (both solid and haematological), autoimmune diseases and mental disorders, and diseases at the single-cell level, as well as at the holistic level. In addition, research is also being conducted on simultaneous multi-molecular profiling of the transcriptome and epigenome from the same cell, along with in-depth analysis of TCR and BCR using single-cell analysis technology, enabling a comprehensive study of the complex network of molecular interactions responsible for activity, disease subtype, and future recurrence. There are plans to expand the research to include spatial studies in this area.

An important thematic aspect is research into the mechanisms of impaired cellular immunity in malignant tumours (solid and haematological) and systemic and organ autoimmune diseases. Current research aims to elucidate the role of individual suppressor proteins and subpopulations of T lymphocytes and monocytes in the pathogenesis, clinical course and response to treatment of these diseases, taking into account genetic predisposition to diseases in the context of polymorphisms of genes encoding molecules that are checkpoints of immune surveillance and protein regulators of the G0/G1 phase of the cell cycle (inhibitor of cyclin-dependent kinases p27Kip1, cyclins D2 and D3) at the transcriptome and proteome levels.

Contact

Laboratory Head

Head: Edyta Pawlak, MD, PhD, DSc (https://orcid.org/0000-0002-0386-7940) is a biotechnologist and graduate of the Faculty of Chemistry at Wrocław University of Science and Technology. Her research identifies new therapeutic targets for cancer, autoimmune diseases, and mental disorders. Over 20 years of professional experience in the field of biotechnology, medical biology, and molecular biology. Professor at the Institute (Polish Academy of Sciences, since 10 March 2022), Head of the Immunopathology Laboratory. Head, principal investigator and investigator in projects of the Ministry of Science and Higher Education, National Science Centre, Foundation for Polish Science, Polish Medical Association, Innovative Economy Operational Programme (European Funds 2007-2013), IRSES, and projects financed by the Wrocław Medical University and Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences. Leader on behalf of IIET PAS of the project Creation and Development of Regional Digital Medicine Centres (ABM/2023/2). Honoured with numerous awards and distinctions. Expert and reviewer in the 4th edition of the ERA PerMed Joint Translational Call 2021 (JTC2021) (ERA-NET on Personalised Medicine) , the 1st edition of the ERA EP PerMed Programme co-financed by ERA-NET and the European Commission to promote innovative translational projects in the field of Personalised Medicine, and an expert in the competition committee within Strategic Area No. 2 financed by the Ministry of Science and Higher Education in the ‘Regional Excellence Initiative’ Programme. Member of the Polish Genetic Society, the European Immunogenetic Federation, the Polish Immunogenetic Society, and The Science Advisory Board. Numerous training courses and workshops, including certified ones, such as: ‘Training in Quality Standards for Polish Biobanks, Part I’ Certificate No. 145, BBMRI-ERIC, Warsaw; ‘QMS1 – Scientific Cooperation – Workshops’, Certificate No. 166, BBMRI, Łódź; ‘QMS2 – Risk Management – workshops’, Certificate No. 200, BBMRI, Łódź. ORCID: 0000-0002-0386-7940; Achievements: 68 scientific publications, IF: 188.643; H-index: 19, and 1 chapter in a book.
Member of Scientific Societies: Polish Society for Immunogenetics (PTiG, since 2008); European Federation for Immunogenetics (EFI, since 11 March 2010, membership number 1703), and Polish Genetic Society (PTG, since 2018).
Member of editorial boards of scientific journals: Frontiers in Oncology – Cancer Molecular Targets and Therapeutics (assistant editor), Frontiers in Psychiatry, Addictive Disorders (guest assistant editor), and Frontiers in Genetics, Behavioral and Psychiatric Genetics (guest assistant editor).
Using the concept of multi-omic research, a network of interactions – both intercellular and intergenetic – between genes and disease is being built. This approach is important for early detection, monitoring and identification of groups at risk of developing the disease. Active cooperation with the Wrocław Medical University, Pomeranian Medical University, University of Wrocław, Institute of Psychology of the Polish Academy of Sciences (Warsaw), the Lower Silesian Centre for Oncology, Pulmonology and Haematology (DCOPiH), the 4th Military Clinical Hospital with Polyclinic in Wrocław, and the Łukasiewicz Research Network – PORT Polish Center for Technology Development (Wrocław).

Team

Scientific Staff:

Specialists:

Technicians:

PhD Students:

Most important scientific achievements
  1. Chronic inflammation accompanying autoimmune diseases is the result of abnormal percentages of circulating Th1, Th17, and Treg lymphocytes, as well as monocyte subpopulations, leading to sustained inflammation; low doses of IL-2 can restore immune balance.
  2. Overexpression of CTLA-4 (one of the immune checkpoints) in circulating lymphocytes leads to a defect in anti-tumour immunity. Immunotherapy of chronic lymphocytic leukaemia (CLL) using a CTLA-4 inhibitor may improve the clinical course of the disease in some patients, while in others it may be an unfavourable strategy, depending on the level of CTLA-4 expression on CLL cells.
  3. A cross-sectional study of inflammatory marker profiling, together with a meta-analysis, suggests that chemokine level abnormalities indicate a subclinical pro-inflammatory state in psychosis. Polymorphisms within genes encoding molecules that regulate the immune response may not only be a critical risk factor, but also determine the profile of clinical symptoms and cognitive functions in schizophrenia.
  4. The relationship between polymorphic variability in the 2q33 region (where the CD28/CTLA-4/ICOS genes are located) and the severity of Graves’ orbitopathy (GO) symptoms and hereditary susceptibility to Graves’ disease. Peripheral sCTLA-4 levels, associated with the severity of GO lesions, are genetically determined and independent of environmental or hormonal factors. Serum sCTLA-4 levels can be considered a useful biochemical marker for the occurrence of severe GO.
Research methods
  • molecular biology: gene expression profiling, gene polymorphism profiling (SNP genotyping, ins/del), microsatellite analysis (STR, VNTR), resequencing (mutation profiling)
  • ELISA tests, Western Blotting
  • flow cytometry
Key equipment
  • device for multiplex analysis of secretome and transcriptome, Luminex xMAP® INTELLIFLEX DRESE System
  • automatic pipetting station Eppendorf epMotion® 5073l
  • PyroMark Q48 Autoprep pyrosequencer
  • Chromium Controller device for preparing libraries with single-cell resolution (single-cell gene expression analysis)
  • system for qualitative and quantitative analysis of genetic material (nucleic acids), DeNovix DS-11 spectrophotometer, and Qubit 2.0 Fluorometer spectrophotometer
  • device for automatic isolation of Maxwell®16 nucleic acids

Most important projects (during the last 10 years)
  • National Science Centre project no. N N402 244935 (21.08.2008-20.02.2012): Dynamics of changes in the CD4+ T cell population (Th1, Th17 and Treg) depending on pro- and anti-inflammatory cytokine profiles in peripheral blood and synovial fluid, and the effect of ex vivo stimulation with the addition of rIL-2 on the examined parameters of the immune system in patients with rheumatoid arthritis (RA) in various phases of the disease and treatment. Project manager: Agata Kosmaczewska, MD, PhD, DSc.
  • National Science Centre project no. N N402 284936 (29.04.2009-28.04.2013): The influence of CTLA-4 protein on the regulation of division activity and apoptosis of peripheral blood leukaemia lymphocytes in patients with chronic B-cell lymphocytic leukaemia (B-PBL). Project manager: Lidia Ciszak, PhD.
  • KNOW project no. 132/2017/KNOW/IITD (11.10.2017-30.10.2018): The relationship between PD1 suppressor molecule overexpression and peripheral Th1, Th17 and Treg lymphocyte imbalance with the progression and clinical course of multiple myeloma. Project manager: Agata Kosmaczewska, MD, PhD, DSc.
  • National Science Centre project no. N N402 285036 (30.04.2009-29.04.2012): The impact of polymorphism of the gene encoding the CTLA-4 suppressor molecule in the donor on the outcome of allogeneic haematopoietic stem cell transplantation (HSCT) and on mRNA levels and protein expression in patients after HSCT. Project manager: Edyta Pawlak, MD, PhD, DSc.
  • POIG project no. 03.02-02-28/13, European Funds 2007-2013, Operational Programme Innovative Economy (01.06.2013-31.12.2015): Creation of a database of immunogenetic information on the Polish population, MultiGenBank. Project manager: Dariusz Wójcik, MSc. Immunopathology Laboratory – task implementation: Creation of an Immunogenetic Module (ImGen).
  • POPC project no. 02.03.01-IP.01-00-006/17, POPC 2014-2020: co-financing for project implementation from the POLSKA CYFROWA Operational Programme (01.08.2018-31.07.2021): Scientific Information Database Supporting Innovative Therapies – BINWIT. Project manager: Krzysztof Pawlik, PhD, DSc. Immunopathology Laboratory – task implementation: Task 3. Information and promotional activities – Edyta Pawlak, MD, PhD, DSc.
  • National Science Centre project no. N N402 465237 (01.01.2009-31.12.2012): Polymorphism of genes encoding IL-2, IL-6, IFN-γ and TGF-β in individuals with schizophrenia and healthy individuals. Project manager: Prof. Irena Frydecka, MD, PhD, DSc. Immunopathology Laboratory – task: Determination of the polymorphic variability profile of genes encoding IL-2, IL-6, IFN-γ, and TGF-β in individuals with schizophrenia and in healthy individuals.
  • National Science Centre project no. 2019/35/D/NZ5/02718 (27.07.2020-26.06.2023): IL-35 expression and its polymorphisms in pregnancy and the risk of miscarriage. Project manager: Anna Sławek, PhD. Immunopathology Laboratory – task: Determination of the relationship between the polymorphic variability profile of EBI3 and IL12A genes and the risk of miscarriage – Edyta Pawlak, MD, PhD, DSc.
Selected publications
  • Frydecka I., Kosmaczewska A., Boćko D., Ciszak L., Wołowiec D., Kuliczkowski K., Kochanowska I.: Alterations of the expression of T-cell related costimulatory CD28 and downregulatory CD152 (CTLA-4) molecules in patients with B-cell chronic lymphocytic lekaemia. Cancer, 2004, 90: 2042-2048 (https://doi.org/10.1038/sj.bjc.6601833).
  • Kosmaczewska A., Świerkot J., Ciszak L., Szteblich A., Chrobak A., Karabon L., Partyka A., Szechinski J., Wiland P., Frydecka I.: Patients with the most advanced rheumatoid arthritis remain with Th1systemic defects after TNF inhibitors treatment despite clinical improvement. Rheumatol Int, 2014, 34: 243-253 (https://doi.org/10.1007/s00296-013-2895-9)
  • Karabon L., Partyka A., Ciszak L., Pawlak-Adamska E., Tomkiewicz A., Bojarska-Junak A., Roliński J., Wołowiec D., Frydecka I., Kosmaczewska A.: Abnormal expression of BTLA and CTLA-4 immune checkpoints molecules in chronic lymphocytic leukaemia patients. Journal of Immunological Research, 2020: 6545921 [12 s.] (https://doi.org/10.1155/2020/6545921).
  • Kosmaczewska A., Świerkot J., Ciszak L., Szteblich A., Szechiński J., Wiland P., Frydecka I.: Exogenous IL-2 controls the balance in Th1, Th17, and Treg cell distribution in patients with progressive rheumatoid arthritis treated with TNF-alpha inhibitors. Inflammation, 2015, 38(2): 765-74 (https://doi.org/10.1007/s10753-014-9987-x).
  • Ciszak L., Frydecka I., Wołowiec D., Szteblich A., Kosmaczewska A.: Patients with chronic lymphocytic leukaemia (CLL) differ in the pattern of CTLA-4 expression on CLL cells: the possible implications for immunotherapy with CTLA-4 blocking antibody. Tumor Biol, 2016, 37 (3): 4143-4157 (https://doi.org/10.1007/s13277-015-4217-1).
  • Kosmaczewska A., Przezdziecka-Dolyk J., Turno-Krecicka A., Ciszak L., Szteblich A., Wegrzyn A., Frydecka I., Misiuk-Hojlo M.: Imbalance in PB IL-17-secreting and regulatory cells in pars planitis is associated with dysregulation of IFN-g-secreting cells, especially in patients with clinical complications. Mediators of Inflammation, 2020: 9175083 [9 s.] (https://doi.org/10.1155/2020/9175083).
  • Kosmaczewska A., Szmyrka M., Ciszak L., Stosio M., Szteblich A., Madej M., Frydecka I., Wiland P.: CD4+CD28null T cells are expanded in clinically quiescent systemic lupus erythematosus and secrete pro-inflammatory IFN-γ depending on the disease activity index. Lupus, 2020, 29 (7): 705-714 (https://doi.org/10.1177/0961203320917749).
  • Pawlak-Adamska E., Frydecka I., Bolanowski M., Tomkiewicz A., Jonkisz A., Karabon L., Partyka A., Nowak O., Szalinski M., Daroszewski J.: CD28/CTLA-4/ICOS haplotypes confers susceptibility to Graves’ disease and modulates clinical phenotype of disease. Endocrine, 2017, 55: 186–199., (https://doi.org/10.1007/s12020-016-1096-1).
  • Pawlak-Adamska E., Daroszewski J., Bolanowski M., Oficjalska J., Janusz P., Szalinski M., Frydecka I.: PPARg2 Ala¹² variant protects against Graves’ orbitopathy and modulates the course of the disease. Immunogenetics, 2013, 65(7): 493-500( https://doi.org/10.1007/s00251-013-0702-0).
  • Daroszewski J., Pawlak E., Karabon L., Frydecka I., Jonkisz A., Slowik M., Bolanowski M.: Soluble CTLA-4 receptor an immunological marker of Graves’ disease and severity of ophthalmopathy is associated with CTLA-4 JO31 and CT60 gene polymorphisms. European Journal of Endocrinology, 2009, 161(5): 787-93 (https://doi.org/10.1530/EJE-09-0600).
  • Kavvoura F.K., Akamizu T., Awata T., Ban Y., Chistiakov D.A., Frydecka I., Ghaderi A., Hiromatsu Y., Ploski R., Walker N., Wang P.W., Ban Y., Bednarczuk T., Chistiakova E.I., Chojm M., Hiratami H., Hank Juo S.H., Karabon L., Katayama S., Kurihara S., Liu R.T., Pawlak E., Taniyama M., Tomita M., Tozaki T., Ioannidis J.P.A.: CTLA-4 gene polymorphisms and autoimmune thyroid diseases: meta-analyses of published data and individual-level data. Journal of Clinical Endocrinology & Metabolism, 2007, 92(8): 3162-70 (https://doi.org/10.1210/jc.2007-0147).
  • Frydecka D., Misiak B., Pawlak-Adamska E., Karabon L., Tomkiewicz A., Sedlaczek P., Kiejna A., Beszłej J.A.: Interleukin-6: the missing element of the neurocognitive deterioration in schizophrenia? The focus on genetic underpinnings, cognitive impairment and clinical manifestation. Eur Arch Psychiatry Clin Neurosci. 2015, 265(6):449-459., doi: 10.1007/s00406-014-0533-5., IF: 4.113
  • Kotowicz K., Frydecka D., Gawęda Ł., Prochwicz K., Kłosowska J., Rymaszewska J., Samochowiec A., Samochowiec J., Szczygieł K., Pawlak-Adamska E., Szmida E., Cechnicki A., Misiak B.: Effects of traumatic life events, cognitive biases and variation in dopaminergic genes on psychosis proneness. Early Interv Psychiatry, 2021, 15(2): 248-255 (https://doi.org/10.1111/eip.12925).
  • Frydecka D., Krzystek-Korpacka M., Lubeiro A., Stramecki F., Stańczykiewicz B., Beszłej J.A., Piotrowski P., Kotowicz K., Szewczuk-Bogusławska M., Pawlak-Adamska, Misiak B.: Profiling inflammatory signatures of schizophrenia: A cross-sectional and meta-analysis study. Brain Behav Immun, 2018, 71: 28-36 (https://doi.org/10.1016/j.bbi.2018.05.002).
  • Pawlak-Adamska E., Nowak O., Karabon L., Pokryszko-Dragan A., Partyka A., Tomkiewicz A., Ptaszkowski J., Frydecka I., Podemski R., Dybko J., Bilińska M.: PD-1 gene polymorphic variation is linked with first symptom of disease and severity of relapsing-remitting form of MS. Journal of Neuroimmunology, 2017, 305: 115-127 (https://doi.org/10.1016/j.jneuroim.2017.02.006).