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:

• RNA Society
• British Society of Cell Biology (BSCB)
• Biochemical Society

Major Funding

• 2023-2026- Biotechnology and Biological Sciences Research Council project grant, Deciphering a novel interplay between RNA and chromatin, £634,167 (joint application with Dr Paola Scaffidi – Francis Crick Institute)
• 2022-2023 – Medical Research Council Mid-range Equipment Grant, £780,011 (Joint application with Prof. Pedro Cutillas)
• 2021-2024- Medical Research Council project grant, The role of RNA mislocalisation in cancer progression, £465,334
• 2017-2023- 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 Prof Pedro Cutillas)

Recent Publications

An ERK1/2-driven RNA-binding switch in nucleolin drives ribosome biogenesis and pancreatic tumorigenesis downstream of RAS oncogene Azman MS, Alard EL, Dodel M et al. EMBO Journal (2023) 42(7)

An mRNA processing pathway suppresses metastasis by governing translational control from the nucleus Navickas A, Asgharian H, Winkler J et al. Nature Cell Biology (2023) 25(7) 892-903

ERG activity is regulated by endothelial FAK coupling with TRIM25/USP9x in vascular patterning D'Amico G, Fernandez I, Gómez-Escudero J et al. Development (Cambridge) (2022) 149(7)

Targeted therapy for LIMD1-deficient non-small cell lung cancer subtypes Davidson K, Grevitt P, Contreras-Gerenas MF et al. Cell Death and Disease (2021) 12(7)

Adipocytes disrupt the translational programme of acute lymphoblastic leukaemia to favour tumour survival and persistence Heydt Q, Xintaropoulou C, Clear A et al. Nature Communications (2021) (1)

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) 125(7) 699-713

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

Team

Postdoctoral Researcher
Dr Zeinab Rekad

Research Technician
Mr Martin Dodel

PhD Students
Ms Federica Capraro, Ms Emilie Alard, Ms Maia Cooper, Ms Zaynah Patel

Biography