NEXT LEVEL Project

Three teams of Instytut Genetyki Człowieka PAN conducting research on hematologic malignancies actively implemented and through participation in the project have improved their scientific performance.

🩸A team from the Department of Molecular and Clinical Genetics led by Prof. Małgorzata Dawidowska has a long-standing collaboration with Universiteit Gent, which was invoved in project.

Prof. Dawidowska delivered within the project a lecture entitled ‘Multi-omics analysis in T-cell acute lymphoblastic leukemia: in search for biological mechanisms and clinical meaning’.

The team organized 2021 dedicated to ‘Acute Lymphoblastic Leukemia’ and also diseeminate research results on international conferences such as ‘3rd Translational Research Conference: Acute Lymphoblastic Leukaemia’ and ‘European Hematology Association (EHA) 2023 Congress’.

As a result of the project's collaboration with partners from Ghent was published joint research paper entitled ‘Multiomics to investigate the mechanisms contributing to repression of PTPRC and SOCS2 in pediatric T-ALL: focus on miR-363-3p and promoter methylation’.

The leukemia team is implementing in the international cooperation 3 hemato-oncological projects:
▪️‘Identification of mTOR pathway deregulation mechanisms alternative to mutations in T-cell acute lymphoblastic leukemia (T-ALL)’
▪️‘Identification of genes and mechanisms underlying the recurrence of T-cell acute lymphoblastic leukemia’
▪️‘CircRNAs involved in mechanisms of malignant transformation and relapse in T-ALL: towards new RNA-based therapies’
and is waiting for evaluation results of another one within programme.

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🧬The Molecular Pathology Department team is led by two P*s: prof. Agnieszka Dzikiewicz – Krawczyk and prof. Natalia Rozwadowska. The team conducts research focusing on the genetics and molecular biology of hematologic malignancies (leukemia, B-cell, and T-cell ).

The team works extensively with the prof. Anke van den Berg's group of UMCG, which invited to participate in the project consortium.

Young researchers from this team have participated to the greatest extent in the mobility offered by the project.

Prof. Dzikiewicz – Krawczyk delivered within the project a lecture ‘Mortal Kombat: fighting MYC in hematologic malignancies’

The team prepared workshop ‘Advanced imaging of biological samples’ and Hematology Day 2022 ‘CAR-T therapy in hematologic neoplasms’ and took part in many networking activities to strengthen international cooperation.

In addition, the researchers participated in conferences such as '4th International Conference on the Long and the Short of Non-Coding RNAs'n and EMBO Workshop ‘Non-coding RNA medicine’.

The project collaboration has resulted in two joint publications:
▪️ 'CRISPR/Cas9 screen for genome-wide interrogation of essential MYC-bound E-boxes in cancer cells'
▪️ 'Inhibition of the glutamate-cysteine ligase catalytic subunit with buthionine sulfoximine enhances the cytotoxic effect of doxorubicin and cyclophosphamide in Burkitt lymphoma cells '
and implementation of hemato-oncological project entitled ’Overcoming CAR-T cell exhaustion by modifying enhancers using CRISPR technology’.

The team submitted 3 projects under , including , which is in the process of evaluation.

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🧪Prof. Maciej Giefing is leader of Department of Cancer Genetics team, which focuses on genomic and epigenomic alterations that contribute to the development of neoplasms, especially classic .

The team is collaborating with Prof. Reiner Siebert's research group at , which was invited to participate in the project.

Prof. Giefing delivered within the project a lecture entitled ‘Unusual expression pattern of the negative NF-ĸB regulator miR-181a and its role in classical Hodgkin lymphoma’.

His team organized workshop ‘DNA bisulfite pyrosequencing – from whole genome to targeted gene methylation analysis' and Hamtology Day 2023 ‘Hodgkin Lymphoma – the great teacher’.

The team disseminated research on such conferences as ‘EMBL Conference Chromatin and epigenetics’ and ‘17th International Conference on Malignant Lymphoma’.

The researchers have published joint paper entitled ‘Identification of two unannotated miRNAs in classic Hodgkin lymphoma cell lines’ and implement hemato-oncology research projects in cooperation with foreign partners:

▪️ 'cfDNA methylome analysis of patients with Hodgkin's lymphoma'
▪️ 'BCOR alterations and the activation of CXCL12 oncogenic pathway in classical Hodgkin lymphoma'
▪️ 'Functional analysis of novel oncomiR candidates in classical Hodgkin lymphoma'.

Recently, the international cooperation with German partners resulted in publication entitled ‘Transcriptional reprogramming by mutated IRF4 in lymphoma’ published in Communication.

All publications that are the result of project cooperation can be found at https://www.nextlevel-h2020.eu/publications/.

projects such as within support improvement of scientific performance of research teams🙂.

photo of A. Dzikiewicz - Krawczyk - archive of Foundation for Polish Science.

Transfer of knowledge was the main course of action to step up research excellence within Project.

🩸We have implemented many activities ensuring transfer of knowledge between highly recognised EU research organisations and Genetyki Człowieka PAN
All partners have delivered 3️⃣ series of lectures:

UMCG - Universitair Medisch Centrum Groningen:
🔹 ‘Biology of B-cell lymphoma’, by Prof. Arjan Diepstra
🔹 ‘Unique features of chromosomal unstable cancer’ by Prof. Floris Foijer
🔹 ‘Deciphering clonal dynamics in acute myeloid leukemia in the context of the immune microenvironment’, by prof. Jan Jacob Schuuring

Universiteit Gent:
🔹 'Modeling mantle cell lymphoma in mice and therapeutic targeting of its cell-of-origin’, by Tim Pieters, PhD
🔹 ‘A dual role for PSIP1 in T-ALL’, by Lisa Demoen, MSc.
🔹 ‘Characterizing and targeting chromatin-associated vulnerabilities in acute lymphoblastic leukemia’, by Prof. Panos Ntziachristos

Universität Ulm:
🔹 'Multi-OMICS analysis in MYC-translocated leukemias and lymphomas: from B-cell development to biomarkers', by Prof. Reiner Siebert
🔹 ‘Genomics and Epigenomics of T-PLL’, by prof. Reiner Siebert
🔹 ‘Genome-wide in vivo screens link regulatory principles and phenotype evolution in T cell leukemia’, by Anja Fischer, Ph.D.

Instytut Genetyki Człowieka PAN:
🔹 ‘Unusual expression pattern of the negative NF-ĸB regulator miR-181a and its role in classical Hodgkin lymphoma’ by Prof. Maciej Giefing
🔹 ‘Multi-omics analysis in T-cell acute lymphoblastic leukemia: in search for biological mechanisms and clinical meaning’, by prof. Małgorzata Dawidowska
🔹 ‘Mortal Kombat: fighting MYC in hematologic malignancies’, by prof. Agnieszka Dzikiewicz – Krawczyk.

The lectures were available to scientists at any level of career development. They provided access to the latest scientific knowledge in the field of hemato-oncology and enabled scientific discussion.

🧪Through the organization of workshops, the project provided the development of specialized qualifications and skills in laboratory techniques. NEXT_LEVEL organized 7️⃣ workshops aimed at doctoral students and post-docs:

🔸 ‘AGO2-IP procedure and data analysis’
🔸 ‘BioIT analysis of RNA, ATAC and ChIP sequencing datasets’
🔸 ‘DNA bisulfite pyrosequencing – from whole genome to targeted gene methylation analysis’
🔸 ‘Methylation analyses using the 450K and EPIC Illumina arrays’
🔸 ‘CRISPR-Cas9, educational and wet lab sessions’
🔸 ‘Dynamic BH3 profiling’
🔸 ‘Advanced imaging of biological samples’

📑To strengthen other skills and develop awareness of other issues corresponding the conduct of scientific research, 4️⃣ Soft Skills Seminars, open to all, were organized, covering the following topics:
◾️ ‘Experiments with the use of laboratory animals – is it so difficult? Practical, ethical and legal aspects of working with laboratory animals’
◾️ ‘Entrepreneurship’
◾️ ‘IPR in research institutions’
◾️ ‘Storytelling’

🔬The project paid special attention to the development of Early Stage Researchers. In order to straighten their qualifications and profession development 'Transferable skills workshop' was provided.

This material reflects only the author's view and the Research Executive Agency of the European Comission is not responsible for any use that may be made of the information it contains.

CRIG - Cancer Research Institute Ghent

Almost 3 years ago we have launched ▶️NEXT_LEVEL project. Its main goal is to step up research excellence in the field of 🩸🧬🧪hemato-oncology of Instytut Genetyki Człowieka PAN and cooperating research organisations: UMCG - Universitair Medisch Centrum Groningen, the Netherlands, Universiteit Gent, Belgium, Universität Ulm, Germany.
The implementation of the project has significantly contributed to the scientific development of the participating institutions, especially the IHG PAS>

🇪🇺The project is funded from Twinning Action of Horizon 2020 programme, which is a great mechanism to support research institutions in widening countries such as Poland.
✋Follow us to learn more about the project’s impact on our teams, participants and organisations. 😀