Dr Zoi Diamantopoulou - Metastasis and circadian rhythm
Introduction
The recent development of liquid biopsies has opened up new directions for monitoring the progression of cancer and the formation of metastasis, bringing us one step closer to effective personalised therapies. Despite these remarkable breakthroughs, metastasis remains the leading cause of cancer-related deaths. Therefore, it is of great significance to investigate the biology of metastasis and identify the critical steps and factors that need to be targeted in order to successfully develop efficient anti-metastatic treatments.
Our work broadly aims to understand how metastasis is regulated by the circadian rhythm. We particularly focus on a very rare cancer cell population that escapes from the primary tumour and spreads throughout the body via the bloodstream to establish new tumours in different locations, named Circulating Tumour Cells (CTCs). We are interested in the circadian rhythm as it has an intriguing role during cancer development and progression. While several studies have shown that the disruption of the circadian rhythm and the resulting misalignment of sleep-wake cycles promote tumour growth, our recent ground-breaking discovery indicates that the metastatic spread of breast cancer occurs during sleep. To further explore how the circadian rhythm drives metastasis, we focus on in vivo mouse models and we employ cutting edge microfluidics and robotic technologies, genetic engineering, next generation sequencing and in vivo imaging systems. We also analyse blood samples from cancer patients to identify circadian rhythm-related molecular vulnerabilities that could be used for the development of novel therapies. Finally, we explore chronotherapy to develop new approaches to drug administration that could be beneficial to cancer patients.
EmailLab Report
Key Publications
Diamantopoulou Z, Gvozdenovic A, Aceto N. A new time dimension in the fight against metastasis. Trends Cell Biol. 2023;10.1016/j.tcb.2023.02.002.
Diamantopoulou Z, Castro-Giner F, Schwab FD, Foerster C, Saini M, Budinjas S, Strittmatter K, Krol I, Seifert B, Heinzelmann-Schwarz V, Kurzeder C, Rochlitz C, Vetter M, Weber WP, Aceto N. The metastatic spread of breast cancer accelerates during sleep. Nature. 2022;607:156-162.
Scheidmann MC, Castro-Giner F, Strittmatter K, Krol I, Paasinen-Sohns A, Scherrer R, Donato C, Gkountela S, Szczerba BM, Diamantopoulou Z, Muenst S, Vlajnic T, Kunz L, Vetter M, Rochlitz C, Taylor V, Giachino C, Schroeder T, Platt RJ, Aceto N. An In Vivo CRISPR Screen Identifies Stepwise Genetic Dependencies of Metastatic Progression. Cancer Res. 2022;82:681-694.
Diamantopoulou Z, Castro-Giner F, Aceto N. Circulating tumor cells: Ready for translation? J Exp Med. 2020;217.
Diamantopoulou Z, White G, Fadlullah MZH, Dreger M, Pickering K, Maltas J, Ashton G, MacLeod R, Baillie GS, Kouskoff V, Lacaud G, Murray GI, Sansom OJ, Hurlstone AFL, Malliri A. TIAM1 Antagonizes TAZ/YAP Both in the Destruction Complex in the Cytoplasm and in the Nucleus to Inhibit Invasion of Intestinal Epithelial Cells. Cancer Cell. 2017;31:621-634.e626.
Biography
Education and Qualifications
2010: PhD, Cellular Biology University of Patras, Greece
2005: BSc, Biology, University of Patras, Greece
Appointments
2023-present: Beatson Research Fellow, CRUK Scotland Institute, Glasgow, UK
2021-2023: Senior Postdoctoral Marie Curie Fellow, Molecular Oncology Group, ETH, Zürich, Switzerland
2019-2021: Senior Postdoctoral Marie Curie Fellow, Cancer Metastasis Group, University of Basel, Switzerland
2018-2019: Senior Cell Biologist, Drug Discovery Unit, CRUK Manchester, UK
2013-2018: Postdoctoral Fellow, Cell Signalling Group, CRUK Manchester Institute, UK
2010-2012: Postdoctoral Fellow, Immupharma and Laboratoire CRRET,CNRS, Universite Paris-Est, France
Honours and Awards
2021 Marie Skłodowska-Curie Postdoctoral Fellowship
2018 The BACR Chris Marshall Prize for Cell Signalling
Recent Publications
2023
Diamantopoulou Z, Gvozdenovic A, Aceto N. A new time dimension in the fight against metastasis. Trends Cell Biol. 2023;10.1016/j.tcb.2023.02.002.
Ginn L, Maltas J, Baker MJ, Chaturvedi A, Wilson L, Guilbert R, Amaral FMR, Priest L, Mole H, Blackhall F, Diamantopoulou Z, Somervaille TCP, Hurlstone A, Malliri A. A TIAM1-TRIM28 complex mediates epigenetic silencing of protocadherins to promote migration of lung cancer cells. Proc Natl Acad Sci U S A. 2023;120(40):e2300489120.
2022
Scheidmann MC, Castro-Giner F, Strittmatter K, Krol I, Paasinen-Sohns A, Scherrer R, Donato C, Gkountela S, Szczerba BM, Diamantopoulou Z, Muenst S, Vlajnic T, Kunz L, Vetter M, Rochlitz C, Taylor V, Giachino C, Schroeder T, Platt RJ, Aceto N. An In Vivo CRISPR Screen Identifies Stepwise Genetic Dependencies of Metastatic Progression. Cancer Res. 2022;82:681-694.
Diamantopoulou Z, Castro-Giner F, Schwab FD, Foerster C, Saini M, Budinjas S, Strittmatter K, Krol I, Seifert B, Heinzelmann-Schwarz V, Kurzeder C, Rochlitz C, Vetter M, Weber WP, Aceto N. The metastatic spread of breast cancer accelerates during sleep. Nature. 2022;607:156-162.
2020
Diamantopoulou Z, Castro-Giner F, Aceto N. Circulating tumor cells: Ready for translation? J Exp Med. 2020;217.
2018
Woroniuk A, Porter A, White G, Newman DT, Diamantopoulou Z, Waring T, Rooney C, Strathdee D, Marston DJ, Hahn KM, Sansom OJ, Zech T, Malliri A. STEF/TIAM2-mediated Rac1 activity at the nuclear envelope regulates the perinuclear actin cap. Nature Communications. 2018;9:2124.
Chatzileontiadou DSM, Tsika AC, Diamantopoulou Z, Delbé J, Badet J, Courty J, Skamnaki VT, Parmenopoulou V, Komiotis D, Hayes JM, Spyroulias GA, Leonidas DD. Evidence for Novel Action at the Cell-Binding Site of Human Angiogenin Revealed by Heteronuclear NMR Spectroscopy, in silico and in vivo Studies. ChemMedChem. 2018;13:259-269.
2017
Diamantopoulou Z, White G, Fadlullah MZH, Dreger M, Pickering K, Maltas J, Ashton G, MacLeod R, Baillie GS, Kouskoff V, Lacaud G, Murray GI, Sansom OJ, Hurlstone AFL, Malliri A. TIAM1 Antagonizes TAZ/YAP Both in the Destruction Complex in the Cytoplasm and in the Nucleus to Inhibit Invasion of Intestinal Epithelial Cells. Cancer Cell. 2017;31:621-634.e626.
Diamantopoulou Z, Gilles ME, Sader M, Cossutta M, Vallée B, Houppe C, Habert D, Brissault B, Leroy E, Maione F, Giraudo E, Destouches D, Penelle J, Courty J, Cascone I. Multivalent cationic pseudopeptide polyplexes as a tool for cancer therapy. Oncotarget. 2017;8:90108-90122.
2015
Whalley HJ, Porter AP, Diamantopoulou Z, White GRM, Castañeda-Saucedo E, Malliri A. Cdk1 phosphorylates the Rac activator Tiam1 to activate centrosomal Pak and promote mitotic spindle formation. Nature Communications. 2015;6:7437.
2012
Pappa EV, Zompra AA, Diamantopoulou Z, Spyranti Z, Pairas G, Lamari FN, Katsoris P, Spyroulias GA, Cordopatis P. Structure-activity studies of lGnRH-III through rational amino acid substitution and NMR conformational studies. Biopolymers. 2012;98:525-534.
Diamantopoulou Z, Kitsou P, Menashi S, Courty J, Katsoris P. Loss of receptor protein tyrosine phosphatase β/ζ (RPTPβ/ζ) promotes prostate cancer metastasis. J Biol Chem. 2012;287:40339-40349.
2011
Pappa EV, Zompra AA, Spyranti Z, Diamantopoulou Z, Pairas G, Lamari FN, Katsoris P, Spyroulias GA, Cordopatis P. Enzymatic stability, solution structure, and antiproliferative effect on prostate cancer cells of leuprolide and new gonadotropin-releasing hormone peptide analogs. Biopolymers. 2011;96:260-272.
2010
Diamantopoulou Z, Bermek O, Polykratis A, Hamma-Kourbali Y, Delbé J, Courty J, Katsoris P. A Pleiotrophin C-terminus peptide induces anti-cancer effects through RPTPβ/ζ. Molecular Cancer. 2010;9:224.
2007
Bermek O, Diamantopoulou Z, Polykratis A, Dos Santos C, Hamma-Kourbali Y, Burlina F, Delbé J, Chassaing G, Fernig DG, Katsoris P, Courty J. A basic peptide derived from the HARP C-terminus inhibits anchorage-independent growth of DU145 prostate cancer cells. Exp Cell Res. 2007;313:4041-4050.
