Research Focus
My lab utilises state-of-art multi-omics methodologies to study how protein synthesis is dysregulated in cancer cells, and how this dysregulation contributes to various stages of cancer progression.
Key Publications
Subcellular mRNA localization regulates ribosome biogenesis in migrating cells. BioRxiv (2020). doi: https://doi.org/10.1101/829739
Methods for monitoring and measurement of protein translation in time and space. Mol Biosyst (2017) 13(12):2477-2488. PMID: 29051942
Global Analysis of mRNA, Translation, and Protein Localization: Local Translation Is a Key Regulator of Cell Protrusions. Dev Cell (2015) 35(3):344-5. PMID: 26555054
Rho-associated kinase (ROCK) function is essential for cell cycle progression, senescence and tumorigenesis. Elife (2016) 5:e12994. PMID: 26765561
Proteomics profiling of interactome dynamics by colocalisation analysis (COLA). Mol Biosyst (2016) 13(1):92-105. PMID: 27824369
Major Funding
- 2017-2022- Medical Research Council Career Development Award, The role of RNA Binding Proteins (RBPs) in breast cancer progression and metastasis, £1,218,815
- 2017-2020- Barts Charity Grant, £370,603.63 (joint application with Dr Pedro Cutillas)
Other Activities
Member of:
- British Society of Cell Biology (BSCB)
- Biochemical Society
Research
Each cell in our body contains the same genetic information, yet this information is read out in diverse manners, allowing different cell types to acquire distinct characteristics. Importantly, the decoding of genetic information is often corrupted in cancer, resulting in undesired characteristics, such as unrestricted proliferation and invasion of malignant cells into other tissues and organs.
The decoding of genetic information occurs sequentially from DNA, via messenger-RNA (mRNA), to proteins, the final and functional products of most genes. My lab is particularly interested in understanding how synthesis of cellular proteins from mRNA is dysregulated in cancer cells through the action of an important group of proteins known as RNA Binding Proteins (RBPs).
Using cutting-edge quantitative proteomics, RNA-seq, and bioinformatics methodologies, along with a variety of cell based and biochemical assays, we study how RBPs regulate RNA in time and space, and how this regulation is altered during cancer progression.
Currently, the lab is focused on four projects:
- The role of mRNA localisation in controlling protein synthesis in normal and malignant cells.
- How ribosome biogenesis is enhanced during malignancy via specific RBPs.
- How oncogenes trigger malignancy by dysregulating the RNA binding activity of specific RBPs.
- How dysregulation of protein synthesis affects antigen presentation and the immune profile of cancer cells.
Ultimately, our goal is to understand how various aspects of cancer progression are mediated by dysregulation of RBPs, in hope of revealing novel therapeutic targets that can be exploited to tackle malignancy.
If you are interested in working/studying in our lab, please e-mail me.
Other Activities
Member of:
- British Society of Cell Biology (BSCB)
- Biochemical Society
Major Funding
- 2017-2022- Medical Research Council Career Development Award, The role of RNA Binding Proteins (RBPs) in breast cancer progression and metastasis, £1,218,815
- 2017-2020- Barts Charity Grant, £370,603.63 (joint application with Dr Pedro Cutillas)
Recent Publications
RBMS1 suppresses colon cancer metastasis through targeted stabilization of its mRNA regulon. Yu J, Navickas A, Asgharian H et al. Cancer Discov (2020) (2)
https://www.ncbi.nlm.nih.gov/pubmed/32513775
Maternal Larp6 controls oocyte development, chorion formation and elevation Hau HTA, Ogundele O, Hibbert AH et al. Development (Cambridge) (2020) 147(7)
DNA repair deficiency sensitizes lung cancer cells to NAD+ biosynthesis blockade Touat M, Sourisseau T, Dorvault N et al. Journal of Clinical Investigation (2018) 128(7) 1671-1687
Mass spectrometry analysis of spatial protein networks by colocalization analysis (COLA) Mardakheh FK (2017) 1636(7) 337-352
Methods for monitoring and measurement of protein translation in time and space Dermit M, Dodel M, Mardakheh FK Molecular BioSystems (2017) 13(7) 2477-2488
RHO binding to FAM65A regulates Golgi reorientation during cell migration. Mardakheh FK, Self A, Marshall CJ J Cell Sci 129(1) 4466-4479
https://www.ncbi.nlm.nih.gov/pubmed/27807006
NAMPT inhibition is a novel synthetic lethal therapeutic approach exploiting nuclear-mitochondrial crosstalk in ERCC1-deficient populations Touat M, Olaussen K, Sourisseau T et al. EUROPEAN JOURNAL OF CANCER (2016) 69(11) S56-S56
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000390503500148&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=612ae0d773dcbdba3046f6df545e9f6a
Proteomics profiling of interactome dynamics by colocalisation analysis (COLA). Mardakheh FK, Sailem HZ, Kümper S et al. Mol Biosyst (2016) 13(1) 92-105
https://www.ncbi.nlm.nih.gov/pubmed/27824369
Microenvironmental Heterogeneity Parallels Breast Cancer Progression: A Histology–Genomic Integration Analysis Natrajan R, Sailem H, Mardakheh FK et al. PLoS Medicine (2016) 13(7)
Rho-associated kinase (ROCK) function is essential for cell cycle progression, senescence and tumorigenesis Kümper S, Mardakheh FK, McCarthy A et al. eLife (2016) 5(7)
For additional publications, please click hereTeam
Postdoctoral Researchers
Dr Maria Dermit
Research Technician
Mr Martin Dodel
PhD Students
Mr Muhammad Syahmi Bin Azman, Mr Elliott Whittaker
Biography
- 2017: Group leader at Barts Cancer Institute, Queen Mary University of London, London, UK.
- 2010-2016: Postdoctoral Research Fellow – Professor Christopher J. Marshall’s laboratory, Institute of Cancer Research, London, UK. (Regulation of polarity during cell migration via RNA localisation and local translation)
- 2006-2010: PhD in Biology – Professor John K. Heath’s laboratory, University of Birmingham, Birmingham, UK. (Feedback regulation of Receptor Tyrosine Kinase signalling by Sprouty and Spred)
- 2004-2006: BSc with Honours Class I in Biochemistry – University of Birmingham, Birmingham, UK.