Job Information
- Organisation/Company: CEITEC MU
- Research Field: Biological sciences; Biological sciences » Biology; Chemistry » Biochemistry
Offer Description
Doctoral study program: Biomedical Sciences
Supervisor: Prof. Marek Mraz, MSc., M.D., Ph.D.
Consultant: Vaclav Seda, PhD
Topic title: Transcription Factors as Regulators of Cell Migration and Microenvironmental Interactions in Chronic Lymphocytic Leukemia
Annotation:
Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western countries and remains largely incurable despite substantial therapeutic advances. Disease progression is critically dependent on interactions between malignant B cells and the lymphoid microenvironment, which provides signals that promote cell survival, proliferation, and resistance to therapy. A central feature of this process is the continuous trafficking of CLL cells between the peripheral blood and protective tissue niches, yet the molecular mechanisms governing this migration remain incompletely understood. This PhD project aims to investigate the role of the FOXO family of transcription factors in regulating CLL cell migration and their contribution to disease pathogenesis. FOXO proteins are key mediators of cellular responses to environmental signals and have emerged as important regulators of immune cell function, survival, and trafficking. However, their specific involvement in the migratory behavior of CLL cells has not been fully elucidated.
The project will focus on identifying FOXO-dependent transcriptional programs associated with migratory CLL cell populations, including clinically relevant CXCR4/CD5-defined subfractions that reflect distinct trafficking states. Using migration-based cellular models, the candidate will characterize the molecular pathways controlled by FOXO proteins and determine how these pathways influence CLL cell movement and interactions with the microenvironment. The project combines cutting-edge molecular and functional approaches, including CRISPR-based genome engineering, transcriptomic and epigenomic profiling (RNA-seq, ChIP-seq), analysis of primary patient samples, testing of inhibitors, and studies in advanced in vitro and in vivo mouse models.
We will employ a broad range of experimental approaches, including flow cytometry, molecular cloning, quantitative PCR, western blotting, and computational analysis of transcriptomic datasets. Functional studies will be used to validate FOXO-regulated genes and signaling pathways involved in CLL migration. Depending on project development, the work may be expanded to include global transcriptomic analyses and the identification of additional transcriptional or signaling regulators that cooperate with FOXO proteins in controlling leukemic cell trafficking.
This project offers an opportunity to address fundamental questions in leukemia biology at the intersection of transcriptional regulation, cell migration, and tumor–microenvironment interactions. The results are expected to provide novel insights into the mechanisms underlying CLL tissue homing and microenvironmental dependence, while identifying potential therapeutic targets aimed at disrupting the protective niches that sustain disease progression and treatment resistance.
Recommended literature:
- Seda et al., 2021, Blood
Seda V, Vojackova E, Ondrisova L, et al. FoxO1-GAB1 axis regulates homing capacity and tonic AKT activity in chronic lymphocytic leukemia. Blood. 2021;138(9):758–772. doi: 10.1182/blood.2020008101. - Burger et al., 1999, Blood
Burger JA, Burger M, Kipps TJ. Chronic lymphocytic leukemia B cells express functional CXCR4 chemokine receptors that mediate spontaneous migration beneath bone marrow stromal cells. Blood. 1999;94(11):3658–3667. - Till et al., 2002, Blood
Till KJ, Lin K, Zuzel M, Cawley JC. The chemokine receptor CCR7 and α4 integrin are important for migration of chronic lymphocytic leukemia cells into lymph nodes. Blood. 2002;99(8):2977–2984. - Calissano et al., 2011, Molecular Medicine
Calissano C, Damle RN, Marsilio S, et al. Intraclonal complexity in chronic lymphocytic leukemia: fractions enriched in recently born/divided and older/quiescent cells. Molecular Medicine. 2011;17:1374–1382. doi: 10.2119/molmed.2011.00360.
Research area: cancer biology, immunology, hematology
Keywords: CLL, therapy, migration
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:
- Master’s degree in Molecular biology, Immunology, Physiology or similar field
- Smart and motivated person that work independently, but also willing to learn from other people in the lab and collaborate.
- Desire to learn new things
- Experience of working in a laboratory
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.
https://is.muni.cz/auth/osoba/101627;
More information about the research group: http://mrazlab.ceitec.cz/
Start date: February 2027 or sooner
Where to apply
Work Location(s)
- Number of offers available: 1
- Company/Institute: CEITEC MU
- Country: Czech Republic
- City: Brno
- Postal Code: 625 00
- Street: Kamenice 753/5
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