Laboratory of Genetics and Epigenetics of Human Diseases

The Laboratory of Genetics and Epigenetics of Human Diseases (LGEHD) was established in July 2020. The Laboratory’s main area of activity is research into the genetic and epigenetic mechanisms regulating the immune response in human diseases, with particular emphasis on the role of immune checkpoints in the development and progression of diseases and in response to treatment. Since 2023, intensive work has also been underway on the development of CAR-T and TCR-T cell therapies.

 

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A key area of LGEHD’s work is research into immunology and cancer immunotherapy. This includes characterising the mechanisms that regulate the activity of immune system cells and identifying potential biomarkers that enable better prediction of disease progression and response to treatment. The laboratory also conducts research into the genetics of haematological cancers and into risk factors that may influence patient outcomes following haematopoietic stem cell transplantation.

An important area of the Laboratory’s work is the development of modern cell therapies for cancer. LGEHD is carrying out the BECAME project – B(e)CMA CAR-T in MM THERAPY (“Implementation of a platform for the production and expansion of CAR-T cells for the treatment of relapsed and refractory multiple myeloma: from vector production to Phase I/II trials”) – funded by the Medical Research Agency. The project focuses on CAR-T therapy utilising a bispecific receptor designed at the IIET PAS, which recognises both BCMA and SLAMF7 simultaneously. This dual antigen recognition is intended to limit the immune escape observed following therapies targeting BCMA alone.

The second pillar of this research area is the development of TCR-T therapies within the TACTiC project – ‘TCR-T and TCR-based CAR-T cell therapies: new possibilities in the treatment of acute myeloid leukaemia’ – funded by the Medical Research Agency as part of the National Recovery Plan. This project focuses on the development of a therapy based on T cells equipped with additional TCR receptors that recognise tumour antigens presented in the HLA context, thereby enabling the targeting of targets inaccessible to conventional CAR-T therapies, including intracellular antigens.

Work on CAR-T and TCR-T therapies has enabled LGEHD to develop expertise that goes beyond laboratory research. The team carries out projects covering the full product development cycle for advanced therapy medicinal products (ATMPs): from construct design and pre-clinical characterisation, through the transfer of the manufacturing process to GMP conditions and the selection of quality control methods, to the preparation of registration documentation and direct scientific consultations with regulatory authorities, including the European Medicines Agency.

The laboratory also carries out the MELBA test; “Analysis of the expression of immune checkpoint biomarkers in patients with advanced skin, gastric and lung cancers”. Its aim is to gain a better understanding of the changes occurring in patients’ immune systems in response to immunotherapy based on the blocking of immune checkpoints, and to identify biomarkers that may be relevant for assessing response to treatment. The study is being conducted in collaboration with the biotechnology company JJP Biologics and the Lower Silesian Centre for Oncology, Pulmonology and Haematology in Wrocław.

In its research, the Laboratory combines techniques from genetics and immunogenetics with methods from cellular immunology. In the field of molecular analyses, the following techniques are utilised: single-cell RNA sequencing (scRNA-seq) with parallel analysis of the TCR repertoire, gene sequencing using NGS, determination of TCR and BCR sequences and clonotypes, assessment of gene methylation by pyrosequencing, gene expression analysis by real-time PCR, and genotyping of polymorphic variants. The laboratory carries out the culture of primary cells and cell lines, including the isolation and expansion of T lymphocytes and other blood cell subpopulations, as well as their genetic modification. Functional assessment includes immunophenotyping by flow cytometry, cytokine assays using ELISA and multiplex (Luminex) methods, cytotoxicity assays, including those based on luminescent signals, and degranulation assays (CD107a).

The research carried out at LGEHD combines cancer genetics, epigenetics and immunology with the development of new immunotherapy strategies. It encompasses both the study of the mechanisms regulating the anti-tumour response and the search for biomarkers of treatment response, as well as the development and pre-clinical characterisation of modern cell therapies.

We carry out our research projects in collaboration with other research centres and medical institutions, including the Lower Silesian Centre for Oncology, Pulmonology and Haematology in Wrocław; the Clinic of Minimally Invasive and Robotic Urology at the University Centre for Urology, Wrocław Medical University; the Department and Clinic of Haematology, Blood Cancers and Bone Marrow Transplantation at the Wrocław Medical University; the First Department and Clinic of Paediatrics, Allergology and Cardiology at the Wrocław Medical University; the Department and Clinic of Pulmonology and Lung Cancer at the Wrocław Medical University; and the Department and Unit for the Treatment of Obesity, Metabolic Disorders and Clinical Dietetics at the Medical University of Poznań.

Through interdisciplinary collaboration, the LGEHD conducts research aimed both at understanding the molecular and immunological mechanisms of diseases and at developing solutions with potential diagnostic, prognostic and therapeutic significance.

Current grants:

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• Medical Research Agency (ABM) project – “Implementation of a platform for the production and expansion of CAR-T cells for the treatment of relapsed and refractory multiple myeloma: from vector production to Phase I/II trials” Acronym: BECAME – B(e)CMA CAR-T in MM THERAPY, 2022/ABM/06/00004. Consortium: Centrum Transferu Technologii IITD sp. z o.o., Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Lower Silesian Centre for Oncology, Pulmonology and Haematology; LGEHD – task no. 6: Optimisation of GMP-compliant lymphocyte transduction and culture
• OPUS 25 grant funded by the National Science Centre: ‘Investigation of the mechanisms regulating alternative splicing of the ALCAM gene and the susceptibility of this molecule to cleavage by shederases present in the tumour microenvironment, and their association with metastasis in bladder cancer and non-small cell lung cancer’; 30 October 2024-29 October 2028, project leader: Marta Wagner, PhD
• OPUS 24 grant in a consortium with the 1st Department and Clinic of Paediatrics, Allergology and Cardiology; “Environmental and epigenetic modifications and the prevention of atopy and allergic diseases in a rural population of children and adults – 20 years of observation”, project leader: Barbara Sozańska, PhD, DSc, task leader: Prof. Lidia Karabon, principal investigator: Marta Wagner, PhD

Grants carried out at the Laboratory:

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• A project by the Medical Research Agency (ABM) funded under the National Recovery Plan – ‘TACTiC: TCR-T and TCR-based CAR-T cell therapies: new possibilities in the treatment of acute myeloid leukaemia’, project leader: Emilia Jaskuła, PhD (2025-2026), ref. no. KPOD.07.07-IW.07-0111/24
• ScaleReady’s G-Rex® Grant Programme – “Development and optimisation of the production process for CAR-T and TCR-T therapies using G-Rex technology”, project leader: Emilia Jaskuła, PhD (2024-2026)
• OPUS 17 grant funded by the National Science Centre: “Immune checkpoints in non-small cell lung cancer – a study of genetic and epigenetic mechanisms regulating mRNA and protein expression”, project leader: Monika Jasek, PhD, DSc (2020-2023; grant no. 2019/33/B/NZ5/03029)
• MINIATURA 6 grant funded by the National Science Centre, grant no. 2022/06/X/NZ7/01793 (2022-2023), “Immunogenicity of COVID-19 vaccination and infection in patients with haematological malignancies”, led by Emilia Jaskuła, PhD
• Applied PhD programme funded by the Ministry of Science and Higher Education (2022-2026), ref. no. DWD/6/0422/2022 ‘The prognostic and therapeutic significance of studies on TP53 gene mutations and 17p deletions in chronic lymphocytic leukaemia’, PhD candidate Anna Sobczyńska-Konefał, MSc, Eng., supervisor Monika Jasek, PhD, DSc
• Project funded by the Count Jakub Potocki Foundation, title: ‘Mechanisms regulating the expression of OX40 and OX40L in non-small cell lung cancer’, 12 July 2024-11 July 2025, project leader: Marta Wagner, PhD
• ‘Investigation of the association between the soluble forms of PD-1/PDL1 and CTLA-4/CD80, TIM3/LAGLS9 and BTLA/HVEM, LAG-3 with the risk of occurrence and progression of bladder cancer’ – a statutory project of the IIET and a statutory project of the Wrocław Medical University, Department of Urology and Urological Oncology, Wrocław
• Count Potocki Foundation Grant: ‘The influence of genetic factors relating to the genes encoding PD-1/PD-L1, which belong to the so-called immune checkpoints, on the risk of developing and the course of renal cancer’, principal investigator: Prof. Lidia Karabon