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

• 2021-2024- Medical Research Council project grant, The role of RNA mislocalisation in cancer progression, £465,334
• 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

The elongation factor eEF1A2 controls translation and actin dynamics in dendritic spines Mendoza MB, Gutierrez S, Ortiz R et al. Science Signaling (2021) 14(7)

Purification and quantitative proteomic analysis of cell bodies and protrusions Dermit M, Mardakheh FK STAR Protocols (2021) 2(7)

A prometastatic splicing program regulated by SNRPA1 interactions with structured RNA elements Fish L, Khoroshkin M, Navickas A et al. Science (2021) 372(7)

Centrosome amplification mediates small extracellular vesicle secretion via lysosome disruption Adams SD, Csere J, D'angelo G et al. Current Biology (2021) 31(7) 1403-1416.e7

A preclinical pipeline to evaluate migrastatics as therapeutic agents in metastatic melanoma Maiques O, Fanshawe B, Crosas-Molist E et al. British Journal of Cancer (2021) (7)

Subcellular mRNA localization regulates ribosome biogenesis in migrating cells DERMIT M, Dodel M, Lee F et al. Developmental Cell (2020) 55(1) 298-313

Maternal Larp6 controls oocyte development, chorion formation and elevation Hau HTA, Ogundele O, Hibbert AH et al. Development (Cambridge) (2020) 147(1)

Rbms1 suppresses colon cancer metastasis through targeted stabilization of its mRNA regulon Yu J, Navickas A, Asgharian H et al. Cancer Discovery (2020) 10(7) 1410-1423

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

Team

Research Technician
Mr Martin Dodel

PhD Students
Mr Muhammad Syahmi Bin Azman, Mr Elliott Whittaker

Biography