Universiteit Leiden

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Sylvia Le Dévédec

Assistant professor

Name
Dr. S.E. Le Dévédec
Telephone
+31 71 527 4285
E-mail
s.e.ledevedec@lacdr.leidenuniv.nl

Dr. Sylvia Le Dévédec is postdoctoral researcher at the Division of Toxicology.

More information about Sylvia Le Dévédec

Biography

Light microscopy has been the guiding theme in my academic career. During my master at the University of Amsterdam in the lab of Prof. R. van Driel (under supervision of Dr. PJ Verschure), I used confocal microscopy to determine the functional organization of nuclear bodies in cancer cells. After a break of few years working in the industry and traveling around the world on a bike, I decided to return to my first interest: look how fascinating are cells when studied through a microscope. During my PhD project in the lab of Prof. B. van de Water at the University of Leiden, I have been interested in how adhesion to the extracellular matrix regulates the behaviour of normal and cancer cells. I used various microscopy techniques including FRAP, FLIP, FRET, TIRF and intravital imaging. In recent years, I have helped for the expansion of the microscopy infrastructure of the Division of Toxicology. Nowadays, all the microscopes are housed at the Cell Observatory, a stimulating environment where bio-imaging and bioinformatics are integrated in a shared facility for Life Science at Leiden University. As the manager of this imaging facility (from the LACDR side), together with Hans de Bont, we coordinate the use of the different microscopes, support all the users and help in the development of new assays, macros for intelligent microscopy and tools for image analysis. During my PhD, I got fascinated by the diversities of dynamics in the cell migration process. To understand these dynamics at the molecular level we established a platform for high-content screening of tumour cell migration which includes: automated microscopy, image processing and data mining. We also established an intravital imaging platform which allows the monitoring of invading tumor cells live in the animal using two-photon microscopy. For this complex type of imaging, we collaborate with experts from Hubrecht (Prof. J. van Rheenen) and LUMC (Dr. Laila Ritsma). At the Cell Observatory, I want to further establish systems microscopy in tumour cell migration/invasion (in 2D/3D and in vivo) in relation to metabolism as the central theme for my research.

Key papers:

1: van Roosmalen W*, Le Dévédec SE*, Golani O, Smid M, Pulyakhina I, Timmermans AM, Look MP, Zi D, Pont C, de Graauw M, Naffar-Abu-Amara S, Kirsanova C, Rustici G, Hoen PA, Martens JW, Foekens JA, Geiger B, van de Water B. (2015) Tumor cell migrationscreen identifies SRPK1 as breast cancer metastasis  determinant. J Clin Invest. * Equal contribution

2: Yizhak K*, Le Dévédec SE*, Rogkoti VM, Baenke F, de Boer VC, Frezza C, Schulze A, van de Water B, Ruppin E. (2014) A computational study of the Warburg effect identifies metabolic targets inhibiting cancer migration. Mol Syst Biol. *Equal contribution

3: Le Dévédec SE, Geverts B, de Bont H, Yan K, Verbeek FJ, Houtsmuller AB, van de Water B. (2012) The residence time of focal adhesion kinase (FAK) and paxillin at focal adhesions in renal epithelial cells is determined by adhesion size, strength and life cycle status. J Cell Sci.

 

4: Le Dévédec SE, Lalai R, Pont C, de Bont H, van de Water B. (2011) Two-photon intravital multicolor imaging combined with inducible gene expression to distinguish metastatic behavior of breast cancer cells in vivo. Mol Imaging Biol.

Projects:

(1) Cell adhesion dynamics :

Understanding the dynamics of cell adhesion in epithelial cells under chemical stress was the primary goal of my PhD project. Together with Prof. AB Houtsmuller (Erasmus Optical Imaging Centre, NL) an expert in confocal microscopy and the study of protein dynamics, we have established an integrated fluorescent bleaching technique (FLIP/FRAP) combined with automated image analysis to study the turnover of adhesion-associated proteins. Clearly the dynamics of those substructures is highly variable in time and space and this variation is controlled by the motility of the proteins that compose the “Adhesome”. Next I focused my research on the dynamics of those adhesions in the migratory behavior of tumor cells. I have collaborated with the bioinformatics group of Dr. FJ Verbeek and together we established an imaging (TIRF) and analysis pipeline to define key predictors of tumor cell migration.

1: Le Dévédec SE, Geverts B, de Bont H, Yan K, Verbeek FJ, Houtsmuller AB, van de Water B. (2012) The residence time of focal adhesion kinase (FAK) and paxillin at focal adhesions in renal epithelial cells is determined by adhesion size, strength and life cycle status. J Cell Sci.

 

2: van Roosmalen W*, Le Dévédec SE*, Golani O, Smid M, Pulyakhina I, Timmermans AM, Look MP, Zi D, Pont C, de Graauw M, Naffar-Abu-Amara S, Kirsanova C, Rustici G, Hoen PA, Martens JW, Foekens JA, Geiger B, van de Water B. (2015) Tumor cell migrationscreen identifies SRPK1 as breast cancer metastasis  determinant. J Clin Invest. * Equal contribution

 

 

(2) Systems microscopy approach to understand tumor cell migration:

Tumor cell migration is a highly orchestrated biological process which is controlled by the continuous cycle of adhesion assembly and disassembly. In the lab of Prof B. van de Water, I have been a key player in establishing a systems microscopy approach to visualize the dynamics of these complexes in highly migrating breast cancer cells and this from in vitro to the whole animal. In addition of having set up a screening pipeline to investigate tumor cell migration, I also defined which mouse model was most suitable to study breast cancer metastasis formation. Recently, in collaboration with Prof. Jacco van Rheenen (Hubrecht, NL), together with Hans de Bont and Chantal Pont, we have established an intravital imaging platform that allows the direct visualization of tumor cell invasion in the primary tumor of animals using a mammary imaging window in combination with two-photon microscopy.

 

1: van Roosmalen W*, Le Dévédec SE*, Zovko S, de Bont H, van de Water B. Functional screening with a live cell imaging-based random cell migration assay.  (2011) Methods Mol Biol. *Equal contribution

 

2: Le Dévédec SE, Yan K, de Bont H, Ghotra V, Truong H, Danen EH, Verbeek F, van de Water B. (2010) Systems microscopy approaches to understand cancer cell migration and metastasis. Cell Mol Life Sci.

 

3: Yan K, Le Dévédec SE, van de Water B and Verbeek FJ . (2009)  Cell tracking and data analysis of in vitro tumor cells from time-lapse image sequences. Proceedings VISAPP

 

4: Le Dévédec SE, van Roosmalen W, Maria N, Grimbergen M, Pont C, Lalai R, van de Water B. (2009) An improved model to study tumor cell autonomous metastasis programs using MTLn3 cells and the Rag2(-/-) gammac (-/-) mouse. Clin Exp Metastasis.

 

Student:

Iris van der Sandt (MSc)

 

(3) Systematic unraveling the spliceosome control of breast cancer progression

Breast cancer is the mostly diagnosed cancer in women worldwide and also the second leading cause of death, mainly due to metastasis formation. To reduce the high breast cancer mortality rate, we need to gain more insight into the disease progression and develop new drugs preventing the metastastic spread. Accumulating evidence suggests that RNA splicing is involved in the different steps of carcinogenesis. Although the critical role of a limited number of splicing factors in cancer has been demonstrated in several studies, the function of the many components of the spliceosome is still unknown. Therefore we want to use a systems microscopy approach to unravel the role of each component of the splicesome (244 splicing factors) in breast cancer cell migration and proliferation. In parallel, we  will verify the relevance of our prmising hits using the Cancer Genome Atlas  (TCGA database) and the data from a cohort of 344 LN breast cancer patients form the Erasmus MC (collaboration with Dr. J. Foekens). Altogether our data will lead to a better insight in the role of splicing factors in the metastatic cascade and could ultimately be used to develop potential therapeutic targets to combat cancer cell dissemination.

Student

Esmee Koedoot (PhD) (PI: Bob van de Water/ co-promotor Sylvia Le Dévédec)

 

(4) Functional imaging to understand metabolic plasticity in breast cancer progression:

A screen for key regulators of tumor cell migration using imaging and siRNA technology has allowed us to identify new regulators of cell motility. One of these hits was not surprisingly a metabolic enzyme which drove me to this exciting question of how does cancer metabolism in general and glycolysis in particular controls the migratory behavior of metastatic cells.  In the last 2 years, I have established a functional imaging platform that makes use of reporter cell lines for different key metabolites using FRET technology. Not only the imaging is optimized but the needed automated image analysis is almost complete (manuscript in preparation).  My goal is to use this methodology to monitor metabolites dynamics and relate this spatiotemporal information to the migratory phenotype of cells in a 2D and 3D environment. A more challenging goal that I am aiming for is to directly visualize in the primary tumor the “metabotype” of invading cells with this FRET technology in combination with the established intravital imaging platform. Using this challenging methodology, I hope to get insight into the metabolic plasticity of tumor cells.

1: Le Dévédec SE, Lalai R, Pont C, de Bont H, van de Water B. (2011) Two-photon intravital multicolor imaging combined with inducible gene expression to distinguish metastatic behavior of breast cancer cells in vivo. Mol Imaging Biol.

 

2: Yizhak K*, Le Dévédec SE*, Rogkoti VM, Baenke F, de Boer VC, Frezza C, Schulze A, van de Water B, Ruppin E. (2014) A computational study of the Warburg effect identifies metabolic targets inhibiting cancer migration. Mol Syst Biol.  *Equal contribution

 

3: Yizhak K, Gaude E, Le Dévédec S, Waldman YY, Stein GY, van de Water B, Frezza C, Ruppin E. (2014) Phenotype-based cell-specific metabolic modeling reveals metabolic liabilities of cancer. Elife.

 

Students

Xiaobing Zhang (PhD)

Elizabeth de Zeeuw (MSc)

Binh Nguyen Nguyen (MSc)

Chiaro G. de Jong (MSc)

(5) Integrating Omics and phenotypic data for determining potential metabolic target in TNBC

I am collaborating with Prof. E. Ruppin, an expert in constraint-based modelling/genome-scale metabolic models and with Prof T. Hankemeier/Dr. Amy Harms for metabolic analysis of breast cancer heterogeneity and plasticity. The initiation and development of cancer is associated with major metabolic alterations, which has given rise to many recent functional studies of cancer metabolism.

Prof E. Ruppin utilize a genome scale metabolic modeling (GSMM) based computational approach to predict and experimentally test leading metabolic drug targets inhibiting TNBC cancer migration. We use transcriptomics, proteomics and functional genomics data to build TNBC GSMM models to identify anti-migratory and anti-invasive metabolic drug targets. We validate the predicted genes using  knockdowns approach in vitro in functional assay.

(6) Chemoinformatics approach to identify novel active compounds to target cancer metabolism

As we are identifying promising metabolic candidate genes for inhibiting tumor cell proliferation and/or cell migration,  I am collaborating with Dr. G. van Western to discover specific metabolic inhibitors that can efficiently target those hits and eventually can be validated in functional assays in vitro and in vivo.

Students:

Oana Diaconescu (MSc) (PI Gerard van Westen)

Jenke Scheen (MSc): (PI Gerard van Westen)

 

Complete List of Published Work in MyBibliography:

http://www.ncbi.nlm.nih.gov/pubmed/?term=le+devedec+s

 

Research Support

10/2015- 10/2019: PhD student supported by the Chinese Scholarship Council on “the Warburg effect at the steering wheel of breast cancer cell migration”.  

 

Assistant professor

  • Wiskunde en Natuurwetenschappen
  • Leiden Academic Centre for Drug Research
  • LACDR/Toxicology

Work address

Science Campus
Einsteinweg 55
2333 CC Leiden
Room number GE2.11

Contact

Publications

  • Geen relevante nevenwerkzaamheden

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