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. Our research is focused on Acute Myeloid Leukemia (AML), a cancer of white blood cells that is characterized by the rapid growth of abnormal myeloid cells. The accumulation of aberrantly proliferating myeloid progenitor cells interferes with the production of normal blood cells, leading to bone marrow failure.
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 tumorigenesis. 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.
In a project funded by the European Research Council (ERC), we are employing novel cellular expression systems of AML oncoproteins in combination with cutting-edge proteomic-, genomic- and transcriptomic approaches in a robust experimental pipeline that enables the rapid characterization of effects of AML oncoprotein expression in a multilayered, global fashion. This is complemented by genome-scale 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.