post-doc (adjunct) at the Department of Molecular Pathology of the IHG PAS

Descrizione

Testo originale dell'annuncio (in inglese)

The characteristic feature of several B-cell lymphomas are translocations involving the immunoglobulin heavy chain (IGH) locus and oncogenes such as MYC, BCL2, BCL6, CCND1. As a result, the translocated oncogenes are placed under the control of IGH enhancers (Eµ, 3’RR1 and 3’RR2) which drive their expression and lymphomagenesis. In our previous study we identified exact regions in IGH enhancers critical for lymphoma cell growth and confirmed transcription of enhancer RNAs (eRNA) from these regions in cell lines and patients. The goal of this project is to develop a novel therapeutic approach for B-cell lymphoma based on targeting the IGH enhancer RNA. To this end, we will conduct a high-throughput screening for small molecules binding to the eRNA transcribed from the essential region in the IGH enhancers. Next, hit compounds will be validated for their effect on lymphoma cell growth and potential toxicity towards normal cells. Finally, selected compounds will be assessed in vivo in mouse xenograft models. Results of our project will indicate novel therapeutic opportunities for treatment of B-cell lymphomas. Our strategy will universally target IGH translocations, regardless of the oncogene involved. This may be especially relevant for the group of so-called double hit B-cell lymphoma patients (with two oncogenes translocated to IGH), who in general respond poorly to current treatment regimens. Results of this pre-clinical proof of concept study will provide novel B-cell lymphoma therapeutics with a direct translation to clinical studies. Key responsibilities: Active participation in the implementation of experimental tasks of the project (validation of the identified hit compounds in lymphoma cell lines: cell culture, molecular analyses and functional studies, assessment of efficacy and safety in vivo in mouse xenograft models ) and analysis of results. Presentation of results at seminars and conferences and participation in writing scientific publications. Writing review papers. Supervision of students.