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CARDIOTOX

Predicting Cardiotoxicity Induced by Kinase Inhibitors: From Systems Biology to Systems Pharmacology

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

CARDIOTOX project word cloud

Explore the words cloud of the CARDIOTOX project. It provides you a very rough idea of what is the project "CARDIOTOX" about.

york ultimately effect track capture university inhibitors consists human time risk computational pharmacology markers expression event quantified sinai limits drugs proteins generation cardiotoxicity training relationship measured independent experimental mrna mathematical dynamically therapeutic serious significantly ct cardiomyocytes cancer network cells identification group signatures adverse decrease fellowship health anti unfortunately on models protein integrating combination himself consolidate disseminate magnitudes mount cardiomyocyte databases technologies pluripotent modifying kinase broaden class disciplinary regulatory clinical kis ki fundamentally exposure treatments stem data predictive researcher fellow dynamical weighted strengthen untargeted leiden innovative career

Project "CARDIOTOX" data sheet

The following table provides information about the project.

Coordinator	UNIVERSITEIT LEIDEN Organization address address: RAPENBURG 70 city: LEIDEN postcode: 2311 EZ website: www.universiteitleiden.nl contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.
Coordinator Country	Netherlands [NL]
Project website	https://www.universiteitleiden.nl/en/staffmembers/coen-van-hasselt
Total cost	242˙929 €
EC max contribution	242˙929 € (100%)
Programme	1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
Code Call	H2020-MSCA-IF-2014
Funding Scheme	MSCA-IF-GF
Starting year	2015
Duration (year-month-day)	from 2015-12-06 to 2018-12-05

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	UNIVERSITEIT LEIDEN UNIVERSITEIT LEIDEN Organization address address: RAPENBURG 70 city: LEIDEN postcode: 2311 EZ website: www.universiteitleiden.nl contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	NL (LEIDEN)	coordinator	242˙929.00
2	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI Organization address address: ONE GUSTAVE L LEVY PLACE BOX 1075 city: NEW YORK postcode: 10029 6574 website: n.a. contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	US (NEW YORK)	partner	0.00

Map

Project objective

Kinase inhibitors (KIs) are a major class of highly effective anti-cancer drugs. Unfortunately, therapeutic use of KIs is often associated with cardiotoxicity (CT), a serious adverse condition which limits their use. This fellowship aims to develop mathematical systems pharmacology models for KI-induced CT. These models will be used to identify predictive CT signatures that will allow to decrease CT risk of new KIs. This innovative multi-disciplinary approach consists of integrating mathematical systems pharmacology modelling, with state-of-the-art experimental data generation. To this aim, KIs with different magnitudes of CT will be selected based on clinical adverse event databases. Human cardiomyocytes derived from pluripotent stem cells will then be treated with the selected KIs and in combination with CT modifying drugs. The effect of these treatments on changes on untargeted mRNA and protein expression will be measured and then analyzed using network modelling. This approach allows identification of key regulatory proteins. The selected proteins will then be quantified over time along with cardiomyocyte health markers. With this data, dynamical models will be developed to capture the relationship between exposure to KIs and the effects on protein expression and cardiomyocyte health over time. Ultimately these models will allow generation of predictive network-based dynamically-weighted signatures for CT. The fellow aims to establish himself as independent researcher in systems pharmacology. Training in state-of-the-art computational and experimental technologies at the leading systems pharmacology group at Mount Sinai in New York will fundamentally strengthen and broaden the experience of the fellow. This project will significantly contribute consolidate the career track of the fellow, foster future collaboration between Mount Sinai and Leiden University, and disseminate training in Europe.

Publications

List of publications.
year	authors and title	journal	last update
2017	Jaehee V. Shim, Bryan Chun, Johan G. C. van Hasselt, Marc R. Birtwistle, Jeffrey J. Saucerman, Eric A. Sobie Mechanistic Systems Modeling to Improve Understanding and Prediction of Cardiotoxicity Caused by Targeted Cancer Therapeutics published pages: , ISSN: 1664-042X, DOI: 10.3389/fphys.2017.00651	Frontiers in Physiology 8	2019-06-18
2017	J.G. Coen van Hassselt, Ravi Iyengar Systems pharmacology-based identification of pharmacogenomic determinants of adverse drug reactions using human iPSC-derived cell lines published pages: 9-15, ISSN: 2452-3100, DOI: 10.1016/j.coisb.2017.05.006	Current Opinion in Systems Biology 4	2019-06-18

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The information about "CARDIOTOX" are provided by the European Opendata Portal: CORDIS opendata.