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PROVIST

PROTEASES VISUALIZATION DURING TUMOR PROGRESSION

Total Cost €

0

EC-Contrib. €

0

Partnership

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Project "PROVIST" data sheet

The following table provides information about the project.

Coordinator
POLITECHNIKA WROCLAWSKA 

Organization address
address: WYBRZEZE WYSPIANSKIEGO 27
city: WROCLAW
postcode: 50-370
website: www.pwr.wroc.pl

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 Poland [PL]
 Project website https://www.cordis.europa.eu/project/rcn/196066_en.html
 Total cost 227˙361 €
 EC max contribution 227˙361 € (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 2016
 Duration (year-month-day) from 2016-01-01   to  2018-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    POLITECHNIKA WROCLAWSKA PL (WROCLAW) coordinator 227˙361.00
2    SANFORD-BURNHAM MEDICAL RESEARCH INSTITUTE US (LA JOLLA CA) partner 0.00

Map

 Project objective

Cancer is one of the most devastating diseases leading to millions of deaths per year, and cancer research is a major topic in many laboratories in academia and industry. The main goal in this proposal is to understand the biology of cancer progression that will lead to the discovery of new, more tailored and personalized anticancer therapies. One of the largest group of enzymes that greatly contribute in cancer progression are proteases. In this project I will leverage the production of highly selective chemical probes to investigate the contribution of medically important proteases in tumor progression in PDX (Patient-Derived Xenograft) mice models using a new analytical technique - mass cytometry. This goal will be achieved via a four-step approach employing techniques from organic chemistry, analytical chemistry, biochemistry and biology making this project multidisciplinary. Proteases that have been chosen for this purpose are caspases, legumain and cathepsins B, L and S for which I will synthesize very specific, small molecule radiolabeled inhibitors suitable for mass cytometry approach. These probes will be first evaluated on recombinant enzymes and simple cell systems and then they will be applied to PDX mice studies. PDX models offer an excellent possibility to study human cancer biology in system most closely related to in vivo pathology. So far there are no reports in the literature regarding the use of mass cytometry in studies of PDX mice models, which makes this project very unique and innovative. This PROVIST project will be performed in Sanford Burnham Medical Research Institute, USA (24-months outgoing phase, prof. Guy Salvesen Lab) and at Wroclaw University of Technology, Poland (12-months return phase, dr. Marcin Drag Lab). The research and training profile of these units fits all the objectives that are included into PROVIST project (scientific research and personal career development).

 Publications

year authors and title journal last update
List of publications.
2017 Wioletta Rut, Marcin Poręba, Paulina Kasperkiewicz, Scott J. Snipas, Marcin Drąg
Selective Substrates and Activity-Based Probes for Imaging of the Human Constitutive 20S Proteasome in Cells and Blood Samples
published pages: 5222-5234, ISSN: 0022-2623, DOI: 10.1021/acs.jmedchem.8b00026
Journal of Medicinal Chemistry 61/12 2020-03-20
2019 Marcin Poreba, Katarzyna Groborz, Wioletta Rut, Milind Pore, Scott J. Snipas, Matej Vizovisek, Boris Turk, Peter Kuhn, Marcin Drag, Guy S. Salvesen
The Activome: multiplexed probing of activity of proteolytic enzymes using mass cytometry-compatible activity-based probes (TOF-probes)
published pages: , ISSN: 1350-9047, DOI: 10.1101/775627
bioRxiv 2020-03-20
2019 Katarzyna Groborz, Monica L. Gonzalez Ramirez, Scott J. Snipas, Guy S. Salvesen, Marcin Drąg, Marcin Poręba
Exploring the prime site in caspases as a novel chemical strategy for understanding the mechanisms of cell death: a proof of concept study on necroptosis in cancer cells
published pages: , ISSN: 1350-9047, DOI: 10.1038/s41418-019-0364-z
Cell Death & Differentiation Epub ahead of print 2020-03-20
2019 Marcin Poreba, Wioletta Rut, Katarzyna Groborz, Scott J. Snipas, Guy S. Salvesen, Marcin Drag
Potent and selective caspase-2 inhibitor prevents MDM-2 cleavage in reversine-treated colon cancer cells
published pages: , ISSN: 1350-9047, DOI: 10.1038/s41418-019-0329-2
Cell Death & Differentiation Epub ahead of print 2020-03-20
2019 Marcin Poreba, Katarzyna Groborz, Matej Vizovisek, Marco Maruggi, Dusan Turk, Boris Turk, Garth Powis, Marcin Drag, Guy S. Salvesen
Fluorescent probes towards selective cathepsin B detection and visualization in cancer cells and patient samples
published pages: , ISSN: 2041-6520, DOI: 10.1039/c9sc00997c
Chemical Science Just accepted 2020-03-20
2019 Marcin Poreba, Katarzyna Groborz, Mario Navarro, Scott J. Snipas, Marcin Drag, Guy S. Salvesen
Caspase selective reagents for diagnosing apoptotic mechanisms
published pages: 229-244, ISSN: 1350-9047, DOI: 10.1038/s41418-018-0110-y
Cell Death & Differentiation 26/2 2020-03-20
2018 Marcin Poreba, Wioletta Rut, Matej Vizovisek, Katarzyna Groborz, Paulina Kasperkiewicz, Darren Finlay, Kristiina Vuori, Dusan Turk, Boris Turk, Guy S. Salvesen, Marcin Drag
Selective imaging of cathepsin L in breast cancer by fluorescent activity-based probes
published pages: 2113-2129, ISSN: 2041-6520, DOI: 10.1039/C7SC04303A
Chemical Science 9 2020-03-20
2016 Marcin Poreba, Rigmor Solberg, Wioletta Rut, Ngoc Nguyen Lunde, Paulina Kasperkiewicz, Scott J. Snipas, Marko Mihelic, Dusan Turk, Boris Turk, Guy S. Salvesen, Marcin Drag
Counter Selection Substrate Library Strategy for Developing Specific Protease Substrates and Probes
published pages: 1023-1035, ISSN: 2451-9456, DOI: 10.1016/j.chembiol.2016.05.020
Cell Chemical Biology 23/8 2020-03-20
2018 Monica L Gonzalez Ramirez, Marcin Poreba, Scott J Snipas, Katarzyna Groborz, Marcin Drag, Guy S Salvesen
Extensive peptide and natural protein substrate screens reveal that mouse caspase-11 has much narrower substrate specificity than caspase-1
published pages: jbc.RA117.001329, ISSN: 0021-9258, DOI: 10.1074/jbc.RA117.001329
Journal of Biological Chemistry 2020-03-20
2017 Paulina Kasperkiewicz, Marcin Poreba, Katarzyna Groborz, Marcin Drag
Emerging challenges in the design of selective substrates, inhibitors and activity-based probes for indistinguishable proteases
published pages: 1518-1539, ISSN: 1742-464X, DOI: 10.1111/febs.14001
The FEBS Journal 284/10 2020-03-20
2017 Marcin Poreba, Guy S Salvesen, Marcin Drag
Synthesis of a HyCoSuL peptide substrate library to dissect protease substrate specificity
published pages: 2189-2214, ISSN: 1754-2189, DOI: 10.1038/nprot.2017.091
Nature Protocols 12/10 2020-03-20
2017 Marcin Poreba, Aleksandra Szalek, Wioletta Rut, Paulina Kasperkiewicz, Izabela Rutkowska-Wlodarczyk, Scott J. Snipas, Yoshifumi Itoh, Dusan Turk, Boris Turk, Christopher M. Overall, Leszek Kaczmarek, Guy S. Salvesen, Marcin Drag
Highly sensitive and adaptable fluorescence-quenched pair discloses the substrate specificity profiles in diverse protease families
published pages: 43135, ISSN: 2045-2322, DOI: 10.1038/srep43135
Scientific Reports 7 2020-03-20

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