Supervisor: Marek Mraz
Information on the supervisor:
H-index 22 (citations at WOS > 1600, 46 publications with IF), currently principal investigator of 4 fundings (AZV, ERC, GAMU, NPÚ), international collaborations: University of Southampton, UCSD, Mayo Clinic, Dana-Farber Cancer Institute, EMBL, University of Turin (student internship available), member of EHA Comitte, reviewer in scientific journals: Blood, Leukemia, Leuk Lymphoma, Leukemia Research;
Annotation: We are looking for a motivated PhD student for a project funded by ERC Grant (Marek Mraz lab, www.ceitec.cz/mrazlab). The project goal is to understand the molecular machinery that regulates the migration of malignant B cells between different niches such as lymphoid and bone marrow niche and peripheral blood. This is of great interests a general mechanism of how migration is regulated in cancer cells, but also especially in chronic lymphocytic leukemia (CLL), which is a disease dependent on the B cell recirculation between different compartments (reviewed in Seda and Mraz, 2015; Seda et al, 2021). In CLL, but also in other lymphomas, the malignant B cells permanently re-circulate from peripheral blood to lymph nodes and back, and blocking this recirculation can be used therapeutically since malignant B cells depend on signals in the immune microenvironment. However, the factors that regulate this are mostly unclear. The lab established several models for in vitro and in vivo studies of microenvironmental interactions and their interplay (unpublished in vivo model; Pavlasova et al. Blood, 2016; Pavlasova et al. Leukemia, 2018; Musilova et al. Blood, 2018; Mraz et al. Blood, 2014; Cerna et al. Leukemia, 2019).
We have identified candidate molecules that might act as novel regulators of the B cell migration or the balance between homing and survival in peripheral blood. This will be further investigated by the PhD student using technics such as genome editing (CRISPR), RNA sequencing, use of primary samples, functional studies with various in vitro and in vivo models. The research is also relevant for understanding resistance mechanisms to BCR inhibitors, pre-clinical development of novel drugs and their combinations (several patents submitted by the lab).
- Seda et al….Mraz FoxO1-GAB1 Axis Regulates Homing Capacity and Tonic AKT Activity in Chronic Lymphocytic Leukemia. Blood 2021 March (epub).
- Pavlasova G, et al…. Mraz M. Ibrutinib inhibits CD20 upregulation on CLL B cells mediated by the CXCR4/SDF-1 axis. Blood. 2016 Sep 22;128(12):1609-13. doi: 10.1182/blood-2016-04-709519. Epub 2016 Aug 1. PMID: 27480113 Free PMC article
- Seda V, Mraz M. B-cell receptor signalling and its crosstalk with other pathways in normal and malignant cells. Eur J Haematol. 2015 Mar;94(3):193-205. doi: 10.1111/ejh.12427. Epub 2014 Sep 13. PMID: 25080849 Review.
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.
More information on CEITEC PhD School website: https://ls-phd.ceitec.cz/ and Research Group website: https://www.ceitec.eu/microenvironment-of-immune-cells/rg115.
In case you are interested. Please, submit your CV and motivation letter via Registration Form.
Listen to the experiences of our PhD students:
- Cosimo Lobello – Medical Genomics Group
- Abigail Rubiato Cuyacot – Functional Genomics and Proteomics of Plants Group
- Karel Škubník – Structural Virology Group