Job Information
Organisation/Company: CEITEC MU
Research Field: Biological sciences » Biology; Chemistry » Biochemistry
Researcher Profile: First Stage Researcher (R1)
Application Deadline: 30 Sep 2026 - 21:50 (UTC)
Country: Czech Republic
Type of Contract: Temporary
Job Status: Full-time
Offer Starting Date: 1 Feb 2027
Is the job funded through the EU Research Framework Programme? Not funded by a EU programme
Is the Job related to staff position within a Research Infrastructure? No
Offer Description
Doctoral study program: Life Sciences
Supervisor: Prof. Marek Mraz, MSc., M.D., Ph.D.
Consultant: RNDr. Josef Vecera, Ph.D.
Topic title: Novel transcriptional regulators of transformation and aggressiveness in indolent B-cell malignancies: therapeutic implications
Annotation:
B-cell malignancies, including chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL), remain incurable diseases despite major advances in targeted therapies. Increasing evidence indicates that malignant B cells acquire profound alterations in chromatin organization, leading to aberrant activation of enhancers and promoters that drive oncogenic gene-expression programs. These changes create a permissive landscape for transcription factors (TFs), key regulators of cell fate, proliferation, and differentiation, to promote tumor growth and survival. Recent studies suggest that TF activity is further shaped by signals from the tumor microenvironment, including post-translational modifications induced by dysregulated signaling pathways. However, the identity of the critical TFs involved and the mechanisms through which they contribute to disease progression, therapeutic resistance, and interactions with the immune microenvironment remain poorly understood. This PhD project aims to uncover the role of novel transcription factors and chromatin-associated regulators in the pathogenesis of CLL, FL, and related B-cell malignancies. Building on our preliminary data, the PhD candidate will investigate TF-driven regulatory networks controlling malignant B-cell survival, proliferation, and communication with surrounding immune cells. Particular emphasis will be placed on transcriptional programs linked to the oncogene MYC and on identifying opportunities for their therapeutic disruption.
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, including in vivo CRISPR screening. The candidate will also evaluate emerging therapeutic strategies targeting transcription factors and chromatin regulators, with the goal of identifying new vulnerabilities that can be exploited for treatment. This interdisciplinary project offers training at the interface of cancer biology, genomics, epigenetics, and translational research, providing an opportunity to contribute to the development of next-generation therapies for B-cell malignancies.
Recommended literature:
- Beekman et al. The reference epigenome and regulatory landscape of chronic lymphocytic leukemia. Nature Medicine 2018
https://pubmed.ncbi.nlm.nih.gov/29785028/ - Sun et al. The immune microenvironment shapes transcriptional and genetic heterogeneity in chronic lymphocytic leukemia. Blood Advances 2022
https://pubmed.ncbi.nlm.nih.gov/35358998/ - Hoferkova et al. Stromal cells engineered to express T cell factors induce robust CLL cell proliferation in vitro and in PDX co-transplantations allowing the identification of RAF inhibitors as anti-proliferative drugs. Leukemia 2024
https://pubmed.ncbi.nlm.nih.gov/38877102/ - Mateos-Jaimez J, Vidal-Crespo A, Charalampopoulou S, Pérez RF, Chapaprieta V, Jiménez-Martínez V, Caviedes-Cárdenas L, Duran-Ferrer M, Espadas G, Sabidó E, Largeot A, Herbst SA, Dietrich S, Boente MB, Alcoceba M, Nadeu F, Ringshausen I, Paggetti J, Moussay E, Colomer D, Campo E, Maiques-Diaz A, Martin-Subero JI. Increased LEF1 protein levels and isoform switching drive cell proliferation in chronic lymphocytic leukemia. Blood. 2025 Dec 25;146(26):3213-3227. doi: 10.1182/blood.2025030129.
Research area: Cancer biology
Keywords: CLL, lymphoma, transcription factor, epigenetics, 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 (AZV 3x, NPO, in the past ERC Starting grant). Dr. Mraz has currently 5 PhD students, with 2finishing soon). international collaborations: University of Southampton, Univ.California- San Diego, Mayo Clinic, Dana-Farber Cancer Institute, EMBL, University of Turin (student internship available), member of EHA Comittee, reviewer in scientific journals: Blood, Leukemia, Leukemia Research; 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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