Oncogenic Mechanisms in AML
The team of Florian Grebien aims to contribute to a better understanding of the molecular mechanisms of leukemia development through the development and use of novel tools for functional evaluation of oncogenic aberrations. Focus of his research is acute myeloid leukemia (AML), a cancer of white blood cells, characterized by the rapid growth of abnormal myeloid cells that accumulate in the bone marrow and interfere with the production of normal blood cells.
The research team of Florian Grebien with Thomas Eder, Stefan Terlecki-Zaniewicz, Luisa Schmidt, Florian Grebien, Jessica Ebner, Anna Skucha, and Johannes Schmöllerl (from left)
The concept of personalized treatment in modern medicine will require an improved molecular understanding of the pathological processes underlying neoplastic initiation and progression. Recent large-scale sequencing studies have revealed a high number of novel genetic lesions that may contribute to carcinogenesis. Thorough experimental validation of these newly identified mutations using standard methodologies, however, cannot keep up with the pace of continuously accelerating data generation. Therefore, the current challenge in modern biology is to adapt and develop novel tools for functional characterization of disease processes.
We are employing novel cellular expression systems in combination with cutting-edge proteomic-, genomic- and transcriptomic approaches to establish a robust experimental pipeline for the rapid characterization of effects of candidate mutations in proteins of interest in a multilayered, global fashion. This is complemented by functional studies to detect specific molecular vulnerabilities that are dependent on the oncogenic mutation of interest. Newly identified molecular mechanisms of mutated alleles are validated using primary patient-derived leukemic cells and translational mouse models of leukemia.
Schematic outline of the established experimental pipeline, inferring the proposed workflow. As indicated by the grey circle, our proposed workflow will start with an unbiased screening encompassing all gene products and will systematically reduce the number of critical candidates to manageable numbers for detailed follow-up studies.
About Florian Grebien
Since 2014 Florian Grebien leads an independent research team at the LBI-CR and is recipient of a prestigious ERC starting grant. He is an expert in the functional analysis of oncogenic pathways and as of March 2016 he has 24 PubMed based publications with an overall impact factor exceeding 250 and more than 1.100 citations. His google scholar profile lists an h-index of 16.
FG did his PhD jointly supervised by Ernst Müllner of the Medical University Vienna and Hartmut Beug of the Research Institute for Molecular Pathology (IMP). For his post-doctoral research he joined the team of Giulio Superti-Furga at the Research Center for Molecular Medicine (CeMM), Vienna.
Please follow the link for a full CV of Florian Grebien.
Florian Grebien's research is funded with a start-up package from institute ressources to support the development of his independent research programme. Since June 2015 his research is in addition funded by the starting grant "ONCOMECHAML" from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 636855). In this five year project he will deploy an innovative combination of modern methods to identify key molecules that can be used as a basis for the development of new therapies. The reviewers of the proposal confirmed in their evaluation statement, that his approach is clinically relevant and feasibly will lead to the development of a novel concept in research.
In addition his research is supported by the Austrian Academy of Sciences through a prestigious DOC fellowship towards Luisa Schmidt and the Austrian Research Promotion Agency (FFG) towards project #857935 entitled "Characterization of small molecules for targeted degradation of WDR5 to interfere with oncogenic MLL activity in cancer".