Supervisor: RNDr. Josef Vecera, Ph.D.
Transcription factors (TFs) are important regulators of cell growth, development, and hematopoietic cell differentiation. Disrupting the mechanisms that are responsible for the proper function of the transcription apparatus can lead to the onset of blood cell malignancies. Abnormal function of TFs due to dysregulation or genomic aberrations are often associated with the development of leukaemias, including chronic lymphocytic leukaemia (CLL) and other B-cell lymphomas. Much evidence from the latest research shows that CLL cells have an extra deregulated chromatin structure and show an increased incidence of activated enhancer and promoter areas, allowing TFs to bind and subsequently aberrantly activate potential oncogenes. Moreover, specific post-translational modification of some TFs have been noted as a result of dysregulated signalling in the leukaemia microenvironment and this also contributes to disease progression. This project should describe the role of candidate TFs in the development and progression of B-cell malignancies with emphasis on CLL while also testing targeted therapy options, e.g. using specific inhibitors of TFs or chromatin modification regulators that are currently available or in development.
We have identified candidate TFs that might act as novel regulators of the B cell survival, proliferation and crosstalk with other immune cells. 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 targeted therapy.
- 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/
- Kipps et al. Chronic lymphocytic leukaemia. Nat Rev 2017 https://pubmed.ncbi.nlm.nih.gov/28102226/
For additional information on our research please go to https://www.ceitec.cz/mikroprostredi-imunitnich-bunek-marek-mraz/rg115.
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@example.com or firstname.lastname@example.org.
More information about CEITEC PhD School are available at http://ls-phd.ceitec.cz/.