How do leukemia oncoproteins drive cancer development?

How can we exploit our knowledge about molecular mechanisms in leukemia development to improve patient management?

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. 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.

Find out more about the research in the FG group…

16.10.2020 We have an exciting PhD position available in Acute Myeloid Leukemia research – find out more here!

News from the Grebien Lab

21.01.2021: Out now – our latest paper by Stefan Terlecki-Zaniewicz et al. in Nature Structural & Molecular Biology linking biomolecular condensation to oncogenic activity of NUP98 fusion proteins – available at https://nature.com/articles/s41594-020-00550-w! Also check out the accompanying News and Views article at https://www.nature.com/articles/s41594-021-00558-w and the blog post of the Nature Research Cancer Community at https://go.nature.com/39645gQ.

12.01.2021: Apply now – more information at http://intercept-mds.eu.

17.11.2020: Congratulations Joey, who did fantastic job defending his thesis on the 17th of November! We hope we can celebrate in person soon, but until then we can have more online celebrations. Good luck for your PostDoc and we’ll definitely stay in touch!

02.10.2020: Congratulations to Stefan, who successfully defended his thesis on the 30th of September! Very well done!

Find out more about what we’re up to…

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