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 can be corrupted in diseases such as 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 (i.e. protein translation) is dysregulated in cancer cells.

Using cutting-edge quantitative proteomics, RNA-seq, and bioinformatics methodologies, along with a variety of cell based and biochemical assays, we study how protein translation is controlled in time and space, and how this regulation is altered during cancer progression.

Currently, the lab is focused on four projects:

• The role of localised translation at the leading edge in controlling cancer cell migration, invasion, and metastasis.
• The role of mRNA localisation in controlling protein translation in normal and malignant cells.
• How oncogenes trigger malignancy by dysregulating gene expression at the level of protein translation.
• How dysregulated protein translation, processing, and turnover affects the immune profile of cancer cells.
• Ultimately, our goal is to understand how various aspects of cancer progression are mediated by spatial and temporal dysregulation of protein synthesis, 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

DNA repair deficiency sensitizes lung cancer cells to NAD+ biosynthesis blockade. Touat M, Sourisseau T, Dorvault N et al. J Clin Invest (2018) 128(2) 1671-1687
https://www.ncbi.nlm.nih.gov/pubmed/29447131

Mass Spectrometry Analysis of Spatial Protein Networks by Colocalization Analysis (COLA). Mardakheh FK (2017) 1636(2) 337-352
https://www.ncbi.nlm.nih.gov/pubmed/28730490

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 Med (2016) 13(2) e1001961
https://www.ncbi.nlm.nih.gov/pubmed/26881778

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(2) e12994
https://www.ncbi.nlm.nih.gov/pubmed/26765561

Global Analysis of mRNA, Translation, and Protein Localization: Local Translation Is a Key Regulator of Cell Protrusions. Mardakheh FK, Paul A, Kümper S et al. Dev Cell (2015) 35(2) 344-357
https://www.ncbi.nlm.nih.gov/pubmed/26555054

Rho kinase inhibitors block melanoma cell migration and inhibit metastasis. Sadok A, McCarthy A, Caldwell J et al. Cancer Res (2015) 75(2) 2272-2284
https://www.ncbi.nlm.nih.gov/pubmed/25840982

Team

Postdoctoral Researchers
Dr Maria Dermit

Research Technician
Mr Martin Dodel

PhD Students
Mr Muhammad Syahmi Bin Azman, Mr Elliott Whittaker

Biography