Anna Sablina Lab

Research focus

​Our research interests are focused on understanding the cooperative interactions that conspire to promote tumorigenic transformation. To discover drivers of cancer development and progression, we create experimental models of cell transformation derived from primary human cells that mimic alterations found in human cancer samples. These models provide a useful platform to delineate pathways involved in cell transformation and to discover new targets for therapeutic intervention. In particular, we are pursuing two research directions:

Post-translational modification of the RAS-like GTPase 
Ras and Rap proteins are closely related small GTPases. Whereas Ras is known for its role in cell proliferation and survival, Rap1 is predominantly involved in cell adhesion and cell junction formation. Ras is the most common oncogene in human cancer - mutations that permanently activate Ras are found in about 25% of all human tumors. On the other hand, activation of Rap1 is known to contribute to tumor metastasis.
We and others recently found that members of the Ras family undergo reversible ubiquitination. Our study revealed that ubiquitination of the RalB GTPases provides the switch for the dual functions of RalB in autophagy and innate immune response, whereas K-Ras ubiquitination dramatically affects its tumorigenic properties. This strongly underlines the importance of reversible ubiquitination in regulation of the Ras-like GTPases. We are exploring how reversible ubiquitination of the Ras-like GTPase is regulated and how ubiquitination of Ras and Rap1 GTPases contributes to cancer development and progression.

The role of large chromosomal deletions in cancer development and progression
The second direction utilizes chromosomal engineering. Somatically acquired chromosomal deletions are extremely common in cancer, in a typical cancer sample, 25% of the genome is affected by chromosome arm-level deletions. Chromosomal deletions may occur over recessive cancer genes, miRNA clusters and/or regulatory regions, where they can confer selective growth advantage. However, a large size of chromosomal deletions makes it difficult to determine the target. As well, some chromosomal deletions may not confer any clonal growth advantage but may occur in regions with a higher susceptibility to DNA rearrangements.
To identify deletion regions critical for human cancer development and progression, we have combined TALEN or CRISPR/Cas9 technologies and in vitro models of cell transformation derived from primary human cells. We introduce targeted chromosomal regions, which are commonly lost during cancer progression, into non-malignant human cells. The created experimental systems, which mimic cancer-associated genetic abnormalities, provide us multiple opportunities. First, it enables us to identify specific chromosomal regions critical for cancer initiation and progression in a high-throughput format. Second, we investigate the cooperative effect of loss of genes, non-coding RNAs, and regulatory elements located within the deleted regions on cell transformation. The proposed model system will also allow us to assess the effect of disruption of the three-dimensional chromosomal network by deletion of specific chromosomal regions on tumorigenic phenotypes. Finally, isogenic cell lines harboring targeted chromosomal alterations will serve as a platform to identify compounds with specificity for particular genetic abnormalities.


Loss of Chromosome 8p Governs Tumor Progression and Drug Response by Altering Lipid MetabolismCai Y* Crowther J* Pastor T Abbasi L Baietti M De Troyer M Vázquez I Talebi A Renzi F Dehairs J Swinnen J Sablina ACANCER CELL, 29, 751-66, 2016* These authors contributed equally
OTUB1 triggers lung cancer development by inhibiting RAS monoubiquitinationBaietti M* Simicek M* Abbasi L Radaelli E Lievens S Crowther J Steklov M Aushev V Martinez Garcia D Tavernier J Sablina AEMBO MOLECULAR MEDICINE, 8, 288-303, 2016* These authors contributed equally
The deubiquitylase USP33 discriminates between RALB functions in autophagy and innate immune responseSimicek M, Lievens S, Laga M, Guzenko D, Aushev V, Kalev P, Baietti M, Strelkov S, Gevaert K, Tavernier JNATURE CELL BIOLOGY, 15, 1220-1230, 2013
Loss of PPP2R2A Inhibits Homologous Recombination DNA Repair and Predicts Tumor Sensitivity to PARP InhibitionKalev P, Simicek M, Vázquez I, Chen l, Soin T, Danda N, Chen WCANCER RESEARCH, 72, 6414-24, 2012
The tumor suppressor PP2A Abeta regulates the RalA GTPaseSablina A, Chen W, Arroyo J, Corral L, Hector M, Bulmer S, Decaprio J, Hahn WCELL, 129, 969-82, 2007

Job openings


Highlighting chromosomal deletion to move cancer research forward

22/10/2016 - By generating cells with chromosomal alterations that mimic human cancers, the team of Anna Sablina (VIB-KU Leuven) allows researchers to assess the role of particular chromosomal deletion in cancer development and progression.

Loss of chromosome 8p governs tumor suppression and drug response

09/05/2016 - Prof. Anna Sablina and her team at VIB/KU Leuven optimized a workflow for the generation of cell lines with targeted chromosomal deletions.

Understanding the specificity of RAL signaling

13/01/2014 - A study by Michal Simicek and Anna Sablina, VIB/KU Leuven, demonstrates that ubiquitylation within effectorbinding domain of RAL GTPases provides the molecular switch for the dual functions of RALB in autophagy and innate immune responses.

Anna Sablina

Anna Sablina

Research area(s)

Model organism(s)


​​PhD: Cancer Research Ctr., Moscow, Russia, 2002
Postdoc: Cleveland Clinic Foundation, Cleveland, USA, 2002-04
Postdoc: Dana Faber Cancer Institute, Boston, USA, 2004-08
VIB Group leader since June 2009

Contact Info

VIB-KU Leuven Center for Cancer BiologyO&N 4, 9e verdCampus GasthuisbergHerestraat 49, bus 912 3000 LEUVENRoute description