Cover Page
The handle
http://hdl.handle.net/1887/138132
holds various files of this Leiden
University dissertation.
Author:
Vlachodimou, A.
Title:
Targeting the adenosinergic system: Ligand binding kinetics and label-free assays
for the study of SLC29A1 transporter and A2B adenosine receptor
Acknowledgements
First of all, I would like to thank my promotors Ad and Laura for guiding me through this fascinating adventure, that eventually turned me into a better scientist and person. Laura, your quest for excellence and solid expertise were valuable to me and this project. You challenged me to work on my shortcomings and guided me with your insightful advice, allowing me to develop my scientific and soft skills. Ad, your down-to-earth attitude and your great knowledge of the field never stopped to amaze me. Even during times that experiments were failing, you managed to keep me calm and challenge me to think alternative approaches; “let’s change gears” as you used to say. Except for the scientific supervision, I really enjoyed our discussions on history and art as well as our visits to the music hall in Haarlem. Last but not least, at the beginning of the PhD I was supervised by an enthusiastic and talented chemist, Julien Louvel. Having been your student and your friend was a honor for me. You will be greatly missed.This project relied greatly on my collaborators. It has been a pleasure to work with you. In particular, I would like to thank Sylvia Le Dévédec (LACDR), Berthold Wroblowski (Janssen) and Ken Jacobson (NIH) for the significant theoretical and practical input. Your contribution was key to complete this thesis.
In addition, I would like to thank all the students and colleagues that I met during this journey. To my students, especially my master students, Peter, Konstantina, Milena, Jara, Miranda and Michiel, working alongside with you was a lot of fun and a unique experience which taught me how to be a supervisor. Your work has contributed to various parts of this thesis, while our inspiring discussions made me think the project from different angles. To my colleagues, thank you for the great fun we had during lab work, conferences, coffee/lunch breaks, lab days and weekends, volleyball games, movie nights, drinks and dinners. I cherish these unforgettable moments. Special thanks to Maarten, Natalia, Lindsey and Xue for sharing PhD experiences and for creating a stress-free environment. To my many old and new office mates; Xuesong, Huub, Indira, Julia, Lance, Arnault, Gerard and Bart, you made all my working days to be special. Thank you for the great (non) work-related conversations. A special thanks to Thea and Henk for sharing your invaluable knowledge on lab “tips & tricks” but mainly on life lessons.
I couldn’t have reached this point without support of my loved ones. Yannis, you have been my rock during these years. You were always there to share our good moments and to help me get through the difficult ones. I simply could not thank you
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enough. To all my friends in Greece, the Netherlands and all over the world, your friendship and support kept me going. Thank you for creating a fun space to vent when needed! I love you all and I am proud to be your friend.
Finally, I would like to thank my family. Without you I couldn’t have achieved this accomplishment, thus no words could really express my gratitude. Mom and dad, I am grateful for always supporting me and encouraging me to follow my dreams. Your unconditional love is my driving force and I always carry it with me. Nikos, except for being my older brother, you are my example to follow and my friend. Thank you all for creating a warm and loving environment for me!
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Oral and poster communications
Aug-2019 11th international BioMedical Transporters Conference – “Membrane transporters and channels: From basic research to drug development and clinical application” Lucerne, Switzerland
poster presentation
Apr-2019 LACDR Spring symposium
Leiden, the Netherlands oral communication Oct-2018 FIGON Dutch Medicine Days
Ede, the Netherlands oral communication(selected poster abstract)
Sep-2018 ITTS Inaugural Conference – “The Transporter Transition”
Vienna, Austria (funded by FIGON travel award) poster presentation
Jun-2018 Gordon Research Seminar in Membrane Transport Proteins – “Membrane Proteins: From Structure to Disease”
Newry, ME, US (funded by ACEA travel award)
oral communication (selected poster abstract)
Jun-2018 Gordon Research Conference in Membrane Transport Proteins – “Transmembrane Transporters in Health and Disease”
Newry, ME, US (funded by ACEA travel award)
poster presentation
Oct-2017 K4DD Meeting – Binding kinetics : Time is of essence
Berlin, Germany poster presentation Aug-2017 10th International BioMedical Transporters Conference –
“SLC Transporters and Ion Channels in Drug Discovery and Preclinical Development”
Lausanne, Switzerland
List of Publications
Vlachodimou A., Heitman L.H., IJzerman A.P. Equilibrative Nucleoside Transporter 1and Adenosine Receptors: Partners in treatment. Manuscript in preparation.
Vlachodimou A., de Vries H., Pasolli M., Goudswaard M., Kim S.-A., Kim Y.-C., Scortichini M., Heitman L.H., Jacobson K.A, IJzerman A.P. Kinetic profiling and
functional characterization of 8-phenylxanthine derivatives as A2B adenosine receptor
antagonists. Manuscript in preparation.
Vlachodimou A., Bouma J., De Cleyn M., Berthelot D., Pype S., Bosmans J.-P., van Vlijmen H., Wroblowski B., Heitman L.H., IJzerman A.P. Kinetic profiling of novel spirobenzo-oxazinepiperidinone derivatives as Equilibrative Nucleoside Transporter 1 inhibitors. Manuscript in preparation.
Vlachodimou A., Konstantinopoulou K., IJzerman A.P., Heitman L.H. Affinity,
binding kinetics and functional characterization of draflazine analogues for human Equilibrative Nucleoside Transporter 1 (SLC29A1). Biochemical Pharmacology
2020, 172, 113747. DOI: 10.1016/j.bcp.2019.113747.
Vlachodimou A., IJzerman A.P., Heitman L.H. Label-free detection of transporter
activity via GPCR signalling in living cells: A case for SLC29A1, the equilibrative
nucleoside transporter 1. Scientific Reports 2019, 9, 13802. DOI:
About the Author
Anna Vlachodimou was born in Thessaloniki, Greece, on December 20th, 1990.She received her Diploma in Pharmacy from the University of Patras, Greece. Her graduation project focused on the synthesis of protein kinase inhibitors sharing the hymenialdisine scaffold. The project was completed at the division of Pharmaceutical Chemistry under the supervision of Dr. Manolis Fousteris and Prof. Sotirios Nikolaropoulos.
In 2013, Anna started the MSc program of Bio-Pharmaceutical Sciences at Leiden University, the Netherlands. During her studies her interests spanned over both theoretical and experimental-oriented aspects of pharmaceutical sciences. She performed a 9-month internship at the division of Medicinal Chemistry at the Leiden Academic Centre for Drug Research (LACDR), under the supervision of Dr. Julien Louvel and Prof. Dr. Ad IJzerman. The project focused on the synthesis of novel antagonists of the A1 adenosine receptor. In 2014, she performed a 6-month internship at the division of Assay and Bioanalytical Sciences at Genmab in Utrecht, the Netherlands, under the supervision of Dr. Dennis Verzijl. There, she developed an image-based cytotoxicity assay for the in vitro evaluation of anti-cancer effects of antibody-drug conjugates. At the end of her studies, she received her MSc degree with Cum Laude distinction.
In 2015, Anna started working as a Ph.D. candidate at the Division of Drug Discovery and Safety (former Division of Medicinal Chemistry) under the supervision of Dr. Julien Louvel, Dr. Laura Heitman and Prof. Dr. Ad IJzerman. In her research, she investigated the concept of target binding kinetics on diverse protein families,
i.e. membrane transporters and GPCRs, as well as their effect on functional efficacy.
During her PhD, Anna presented her work at several national and international conferences. She was an invited speaker at various occasions, including FIGON Dutch Medicine Days 2018 and Gordon Research Seminar “Membrane Transport Proteins” 2018.
Currently, Anna works as a Study Director at Charles River Laboratories in ‘s-Hertogenbosch, the Netherlands.
