Anna Sablina Lab

Research focus

The RAS pathway is the most frequently activated signaling node in human disease. Despite intensive efforts, effective therapeutic strategies for RAS-driven disease remain daunting. Elucidation of the mechanisms of RAS activation promises to lead toward novel therapeutic approaches to inhibit RAS activity, and will permit identification of patients who might benefit from RAS pathway inhibitors. Our preliminary studies show that reversible ubiquitylation controls RAS activity by altering its interaction network, thus representing a conceptually novel mechanism of RAS regulation.

Our initial steps towards the understanding of the RAS ubiquitylation machinery have shown that positive regulators of RAS ubiquitylation are frequently mutated or down-regulated in human disease, such as Noonan Syndrome, Schwannomatosis, meningioma, and several types of human cancer. In contrast, OTUB1, a negative regulator of RAS ubiquitination, is commonly amplified and overexpressed in wild-type RAS epithelial cancers.

Our goal is to elucidate the role of the ubiquitin system in RAS-associated disease. We plan to unravel the molecular machinery controlling RAS ubiquitylation and ascertain alterations of the identified machinery in RAS-driven disease. To assess the functional impact of these alterations, we will create genetically modified mouse models and CRISPR-engineered human cell models. We will employ cutting-edge proteomic approaches to determine how disease-associated dysregulation of RAS ubiquitylation perturbs RAS interactions and signalling. Using a synthetic biologic approach, we will obtain insights into the mechanisms by which ubiquitylation modulates RAS interactions. It is significant that, in contrast to the majority of known RAS regulators, the ubiquitin enzymes are “druggable”, which implicates them as promising targets for inhibiting RAS activity. Thus, our studies could lead to new ways of defeating RAS-driven disease.​

Publications

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, Munck S, Chen l, Soin T, Danda N, Chen W, Sablina ACANCER 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

News

ERC Consolidator Grants for three VIB scientists: boost for innovative research

28/11/2017 - The European Research Council (ERC) has awarded 3 VIB scientists a consolidator grant: Anna Sablina, Sarah-Maria Fendt and Massimiliano Mazzone, all from the VIB-KU Leuven Center for Cancer Biology.

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)

Bio

​​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