Offer Description
Doctoral study program: Biomedical Sciences
Supervisor: Prof. Marek Mraz, MSc., M.D., Ph.D.
Topic title
RNA Networks Driving Aggressiveness and Transformation of „Indolent“ B cell Malignancies
Annotation
Marek Mraz research group has a long-term interest in non-coding RNAs and microenvironmental interactions of malignant B cells, and this research has been supported by an ERC Starting grant (2019-2024) and GACR EXPRO (2025-2029).
Follicular lymphoma (FL) is the most common indolent B-cell lymphoma and chronic lymphocytic leukemia (CLL) is the most common adult leukemia, and both are typically characterized by a slow clinical course. However, approximately 20% of FL and 15% of CLL patients experience aggressive disease behavior and/or undergo histological transformation into diffuse large B-cell lymphoma (DLBCL), a highly aggressive malignancy associated with poor clinical outcomes. Despite its major clinical significance, the molecular mechanisms underlying disease progression and transformation remain incompletely understood. Improved understanding of these processes is essential for the development of predictive biomarkers and more effective therapeutic strategies.
This PhD project aims to uncover how non-coding RNA (ncRNA) regulatory networks contribute to the aggressiveness and transformation of FL. The project builds on the long-standing expertise of the research group in non-coding RNA biology and tumor–microenvironment interactions, supported by prestigious ERC Starting Grant and GAČR EXPRO funding. Previous work from the group has identified multiple microRNAs involved in the regulation of malignant B-cell biology, while the role of long non-coding RNAs (lncRNAs) in FL remains largely unexplored.
To address this challenge, the project will leverage unique transcriptomic datasets generated from paired patient samples of FL/CLL and transformed FL/CLL as well as samples obtained before and after disease relapse. These analyses have already revealed a set of candidate microRNAs and lncRNAs associated with disease progression, providing a strong foundation for mechanistic studies. The candidate will investigate how these ncRNAs regulate key cellular processes linked to lymphoma aggressiveness, including proliferation, survival, adaptation to the microenvironment, and resistance to therapy. A major objective of the project will be the integration of non-coding RNA biology with transcriptional regulation. The student will identify transcription factors responsible for aberrant ncRNA expression and define the regulatory networks connecting transcription factors, ncRNAs, and downstream oncogenic pathways. This systems-level approach will provide novel insights into the molecular circuits driving lymphoma evolution and transformation. The project combines state-of-the-art experimental and computational methodologies, including CRISPR interference, RNA pulldown assays, transcriptomic profiling, molecular biology techniques, functional studies in cellular and animal models, and the analysis of primary patient samples. Through these approaches, the candidate will define the molecular functions and interaction partners of candidate ncRNAs and assess their contribution to disease progression.
This interdisciplinary project offers training in cancer biology, functional genomics, RNA biology, bioinformatics, and translational research. The results are expected to advance our understanding of lymphoma evolution, identify biomarkers associated with aggressive disease and transformation, and uncover novel therapeutic targets for patients at high risk of disease progression.
Recommended literature
- Filip D, Litzmanova K, Michaelou A, Kledus F, Devan J, Boudny M, Hoferkova E, Sharma S, Seda V, Zeni PF, Borsky M, Matulova K, Kren L, Oppelt J, Blavet N, Hejret V, Urik M, Mareckova A, Rimsza LM, Kamaradova K, Belada D, Sykorova A, Mocikova H, Trneny M, Prouzova Z, Evans AG, Danilov A, Horn H, Ott G, Staber P, Mayer J, Friedberg JW, Janikova A, Mraz M. Repression of miR-29 via MYC leads to increased CD40 signaling in transformed follicular lymphoma. Leukemia. 2026 Apr;40(4):759-772
- Devan J, Janikova A, Mraz M. New concepts in follicular lymphoma biology: From BCL2 to epigenetic regulators and non-coding RNAs. Semin Oncol. 2018 Oct;45(5-6):291-30. https://pubmed.ncbi.nlm.nih.gov/30360879/
- Zeni and Mraz LncRNAs in adaptive immunity: role in physiological and pathological conditions. RNA Biol. 2021 May;18(5):619-632. https://pubmed.ncbi.nlm.nih.gov/33094664
- Mattick JS, et al. Long non-coding RNAs: definitions, functions, challenges and recommendations. Nat Rev Mol Cell Biol. 2023 Jun https://pubmed.ncbi.nlm.nih.gov/36596869/
- Sharma et al. …Mraz. miR-29 Modulates CD40 Signaling in Chronic Lymphocytic Leukemia by Targeting TRAF4: an Axis Affected by BCR inhibitors. Blood 2021. https://pubmed.ncbi.nlm.nih.gov/33171493/
- Musilova K, Mraz M. MicroRNAs in B-cell lymphomas: how a complex biology gets more complex. Leukemia. 2015 May;29(5):1004-17
Research area: cancer biology
Keywords: lymphoma, CLL, lncRNA, microenvironment
Funding for the PhD candidate
In the academic year 2026/27 the net income of the CEITEC PhD School student is expected to be at least CZK 29,400 (approx. EUR 1215)
Part-time salary (min. 0,5 FTE) on EHA grant/AZV/GACR grants + doctoral scholarship + CEITEC PhD School scholarship.
Requirements on candidates
Motivated smart people that have the “drive” to work independently, but also willing to learn from other people in the lab and collaborate.
Candidates should have a master’s degree in Molecular biology, Biochemistry, or similar field and have deep interest in molecular biology and cancer cell biology.
Information about the supervisor
H-index 30 (citations > 3500, 50 publications with IF), currently principal investigator of 4 grants (GACR EXPRO, AZV 2x, NPO, in the past ERC Starting grant). Dr. Mraz has currently 5 PhD students, with 2 finishing soon. international collaborations: University of Southampton, Univ.California- San Diego, Mayo Clinic, Dana-Farber Cancer Institute, EMBL, University of Turin (student internship available), Univ. Southampton, UK, member of EHA Comittee, reviewer in scientific journals: Blood, Leukemia, Leukemia Research.
Prof. Mraz belongs to one of the most nationally and internationally recognized researchers in hematology, which is illustrated by the national award Czech Head, and award Neuron for Czech scientists. He is also the recipient of Research award by European Hematology Association, and an ERC grant holder.
More information about the research group: http://mrazlab.ceitec.cz/
Start date: February 2027 or sooner
Sign-up link: https://www.ceitec.eu/rna-networks-driving-aggressiveness-and-transformation-of-indolent-b-cell-malignancies/t11794
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