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VulneraBAP1 SIGNED

Mechanism and vulnerability of BAP1 loss in tumor metastasis

Total Cost €

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EC-Contrib. €

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Partnership

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 VulneraBAP1 project word cloud

Explore the words cloud of the VulneraBAP1 project. It provides you a very rough idea of what is the project "VulneraBAP1" about.

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Project "VulneraBAP1" data sheet

The following table provides information about the project.

Coordinator
DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG 

Organization address
address: IM NEUENHEIMER FELD 280
city: HEIDELBERG
postcode: 69120
website: www.dkfz.de

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 Germany [DE]
 Total cost 171˙460 €
 EC max contribution 171˙460 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2017
 Funding Scheme MSCA-IF-EF-RI
 Starting year 2018
 Duration (year-month-day) from 2018-07-01   to  2020-06-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG DE (HEIDELBERG) coordinator 171˙460.00

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 Project objective

Kidney cancer is among the ten most prevalent cancers arising in Western countries, with clear-cell renal cell carcinoma (ccRCC) being the most frequent subtype (75%). About 30% of ccRCC patients present with metastatic disease at diagnosis, and another 30% will develop metastases after surgery. When metastatic, ccRCC remains largely incurable.

I recently discovered that the tumor suppressor BAP1 (BRCA1-associated protein 1) is inactivated in 15% of ccRCCs (Peña-Llopis et al. Nat. Genet. 2012). Notably, I found that mutations in BAP1 are mutually exclusive with mutations of the tumor suppressor gene PBRM1, and loss of BAP1 was associated with higher tumor grade, activation of mTORC1, and poorer overall patient survival, whereas tumors with PBRM1 loss were associated with lower tumor grade and better overall survival. This first molecular genetic classification of ccRCC may have tangible clinical implications, since tumors with BAP1 loss display in general more aggressive pathological features and are more prone to metastasize. However, the molecular mechanism through which BAP1 loss induces metastasis and tumor aggressiveness remains elusive.

In this study, I aim to investigate the molecular mechanism of repression of a miRNA cluster involved in metastasis by BAP1 and identify therapeutic opportunities. Specifically, I will (1) supervise a PhD student (supported by a grant I was recently been awarded) in the identification and characterization of the BAP1 protein complex that binds at the miRNA cluster promoter; and (2) I will uncover the genetic vulnerabilities of BAP1 loss by a synthetic lethality strategy. These studies will facilitate attainment of my long term career goal to become a group leader and a fully independent investigator.

 Publications

year authors and title journal last update
List of publications.
2019 Max Fleischmann, Daniel Martin, Samuel Peña-Llopis, Julius Oppermann, Jens von der Grün, Markus Diefenhardt, Georgios Chatzikonstantinou, Emmanouil Fokas, Claus Rödel, Klaus Strebhardt, Sven Becker, Franz Rödel, Nikolaos Tselis
Association of Polo-Like Kinase 3 and PhosphoT273 Caspase 8 Levels With Disease-Related Outcomes Among Cervical Squamous Cell Carcinoma Patients Treated With Chemoradiation and Brachytherapy
published pages: , ISSN: 2234-943X, DOI: 10.3389/fonc.2019.00742
Frontiers in Oncology 9 2020-01-29

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