PhD topic / PhD position: REGULATION OF CELL MIGRATION IN B CELL LEUKEMIAS AND LYMPHOMAS

Supervisor:  Assoc. Prof. Marek Mraz, MSc., M.D., Ph.D.

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 specally in chronic lymphocytic leukemia (CLL), which is a disease dependent on the B cell recirculation between different compartments (reviewed in Seda and Mraz, 2015). 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lab established several models for in vitro and in vivo studies of microenvironmental interactions and their interplay (unpublished in vivo model; Pavlasova et al.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).

Recommended literature:

• Seda et al….Mraz FoxO1-GAB1 Axis Regulates Homing Capacity and Tonic AKT Activity in Chronic Lymphocytic Leukemia. Blood 2021 March (epub). https://pubmed.ncbi.nlm.nih.gov/33786575/
• 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.

Applications should include: a CV, a scanned copy of the Masters or an official letter certifying its completion, brief motivation letter, and contacts for at least two references should be sent via email [email protected]  or [email protected] .

More information about CEITEC PhD School are available at http://ls-phd.ceitec.cz /.