MARDAKHEH LAB

Barts Cancer Institute

What do we do?

Our lab studies how gene expression is post-transcriptionally dysregulated in various cancers, leading to generation and progression of malignancy. In particular, we are interested in  RNA Binding Proteins (RBPs) that play a role in cancer development and progression by controlling localisation, stability, and translation of different functional categories of transcripts:
 

Why do we do it?
Cancer is a disease of gene expression dysregulation. Importantly, it is now clear that a significant degree of this dysregulation occurs post-transcriptionally i.e. after synthesis of RNA from DNA. RBPs are the main post-transcriptional regulators of gene expression, controlling all aspects of RNA life cycle such as processing, modification, transport, translation, and decay. However, it is still largely unclear how different RBPs are dysregulated during the course of cancer, in order to promote different aspects of malignancy. Crucially, recent advances in RNA therapeutics mean that a more mechanistic understanding of RBPs contribution towards malignancy can potentially  be used to develop novel therapies for tackling different cancers.
 

How do we do it?

We use various omics technologies to study the role of RBPs in different aspects of post-transcriptional gene expression regulation. In particular, we are experts in Mass Spectrometry (MS) based proteomics, using various MS techniques to quantitatively study processes such as protein translation and RNA-Protein interactions, as well as combining proteomics data with RNA-sequencing to reveal the intricacies of post-transcriptional regulation by RBPs. 
 

Selected publications:

• Azman MS, Dodel M, Capraro F, Faraway R, Dermit M, Fan W, Ule J, Mardakheh FK*. (2021) An RNA-binding switch drives ribosome biogenesis and tumorigenesis downstream of RAS oncogene. BioRxiv (https://doi.org/10.1101/2021.12.16.472890).

• Dermit M , Dodel M , Lee FCY, Azman MS , Schwenzer H, Jones JL, Blagden SP, Ule J, Mardakheh FK*. (2020) Subcellular mRNA localization regulates ribosome biogenesis in migrating cells. Developmental Cell. 55(3):298-313. 

• Johnny Yu, Albertas Navickas, Hosseinali Asgharian, Bruce Culbertson, Lisa Fish, Kristle Garcia, John Paolo Olegario, Maria Dermit, Martin Dodel, Benjamin Hanisch, Yikai Luo, Ethan M Weinberg, Rodrigo Dienstmann, Robert S Warren, Faraz K Mardakheh and Hani Goodarzi. (2020) RBMS1 suppresses colon cancer metastasis through targeted stabilization of its mRNA regulon. Cancer Discovery 10:1410–23.

• Dermit M, Dodel M, Mardakheh FK*. (2017) Methods for monitoring and measurement of protein translation in time and space. Mol Biosyst. 13:2477-2488. 

• Mardakheh FK*, Paul A, Kümper S, Sadok A, Paterson H, Mccarthy A, Yuan Y, and Marshall CJ. (2015) Global analysis of mRNA, translation, and protein localizations: local translation is a key regulator of cell-protrusions. Developmental Cell. 35:344-57.