PROJECT
SUPERVISORS

Project Supervisor

Florian Grebien

Background

I studied Microbiology and Genetics at the University Vienna. As I was very interested in developmental biology, I joined the groups of Ernst Müllner (Medical University Vienna) and Hartmut Beug (IMP Vienna) to study how developing erythrocytes regulate their cell size and respond to extracellular stimuli during my PhD work. The studies of normal hematopoiesis sparked my interest in investigating aberrant blood cell development, which can lead to cancer.

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As a Postdoc, I decided to switch fields and joined the laboratory of Giulio Superti-Furga at the Center for Molecular medicine of the Austrian Academy of Sciences in Vienna. In this evironment, I trained in biochemistry of protein kinases and learned how to use Mass Spectromenty and other global approaches to study physiological processes. From 2014-2018, I was a PI at the Ludwig Boltzmann Institute for Cancer Research in Vienna, and since January 2018, I am heading the Institute for Medical Biochemistry at the University of Veterinary Medicine in Vienna.

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Research

In the Grebien laboratory, we use a multidisciplinary approach to dissect molecular mechanisms that underlie cancer development. The focus of our research is Acute Myeloid Leukemia (AML), a cancer of white blood cells that is characterized by the rapid growth of abnormal myeloid cells. Their accumulation in the bone marrow interferes with the production of normal blood cells, leading to dysfunctional hematopoiesis. AML development is caused by dysfunction of factors that are required to regulate normal blood development.

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Recent genomic studies have shown that leukemia oncoproteins often arise from mutations in genes that encode transcription factors and epigenetic modulators. We believe that oncogenic mechanisms of AML fusion proteins are hard-wired in specific networks of physical, genetic and epigenetic interactions with key effector proteins. Functional exploration of these networks will provide new insights into cellular processes that depend on critical effector proteins of AML oncoproteins.

Thus, the goal of our research is a comprehensive systems-level investigation of oncogenic mechanisms employed by AML oncoproteins. By combining novel cell line and animal models of AML with cutting-edge proteomic-, epigenomic- and transcriptomic approaches, we have established a robust experimental pipeline for the functional characterization of AML oncoproteins in a multilayered fashion. This is complemented by functional studies in mouse models and primary human samples to detect molecular vulnerabilities that are dependent on the oncogenic mutation of interest.

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Publications

Terlecki-Zaniewicz S et al. Biomolecular condensation of NUP98 fusion proteins drives leukemogenic gene expression. Nature Structural & Molecular Biology. 2021

Schmoellerl J et al. CDK6 is an essential direct target of NUP98-fusion proteins in acute myeloid leukemia. Blood. 2020

Skucha A et al. MLL-Fusion-Driven Leukemia Requires SETD2 to Safeguard Genomic Integrity. Nature Communications. 2018