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PROVIST

PROTEASES VISUALIZATION DURING TUMOR PROGRESSION

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

PROVIST project word cloud

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

enzymes xenograft guy profile synthesize deaths purpose 12 models dr usa return reports leverage salvesen provist recombinant fits small diseases possibility anticancer devastating pdx laboratories technique scientific proteases molecule university drag 24 outgoing human organic regarding closely personalized literature caspases therapies innovative industry burnham radiolabeled progression units academia mice pathology legumain medical medically cell contribution chemical lab biology excellent suitable first career employing group marcin cytometry personal sanford mass techniques patient cancer understand discovery wroclaw tumor multidisciplinary inhibitors selective chemistry biochemistry cathepsins prof poland analytical performed probes millions months training vivo chosen

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 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.	PL (WROCLAW)	coordinator	227˙361.00
2	SANFORD-BURNHAM MEDICAL RESEARCH INSTITUTE SANFORD-BURNHAM MEDICAL RESEARCH INSTITUTE Organization address address: NORTH TORREY PINES ROAD 10901 city: LA JOLLA CA postcode: 92037 1005 website: www.sanfordburnham.org contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	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

List of publications.
year	authors and title	journal	last update
2017	Wioletta Rut, Marcin PorÄ™ba, Paulina Kasperkiewicz, Scott J. Snipas, Marcin DrÄ…g 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 DrÄ…g, Marcin PorÄ™ba 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 cathepsinÂ 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, NgocÂ Nguyen Lunde, Paulina Kasperkiewicz, ScottÂ J. Snipas, Marko Mihelic, Dusan Turk, Boris Turk, GuyÂ 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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