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UreaCa SIGNED

Deciphering the metabolic roles of the urea-cycle pathway in carcinogenesis for improving diagnosis and therapy

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 UreaCa project word cloud

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

characterising    identifiable    diagnosis    poor    metabolism    progression    enzymes    molecular    diagnostic    phenotypes    systemic    patient    therapy    cancer    nitrogen    tumour    scientific    flux    cellular    synthesis    metabolomic    leads    pursue    dysregulation    ucd    blind    incorporate    signatures    correlating    degradation    anabolic    almost    excrete    metabolic    cell    metabolically    ago    liver    demonstrated    scientist    hypothesis    physician    components    treatment    alteration    reducing    initiation    net    express    biochemical    uc    cancers    cycle    augmenting    global    implications    catabolic    harbours    energy    biomarkers    surprisingly    complete    phenomenon    provides    drug    tissues    predict    macromolecules    altered    functions    urea    explore    spot    prognosis    causing    advantage    utility    training    carcinogenesis    hypothesise    effect    monitoring    combinations    genomic    considerable    expression    warburg    occurs    peptidomic    efficacy    causally    translational    therapeutic    waste    mammals    multiple   

Project "UreaCa" data sheet

The following table provides information about the project.

Coordinator
WEIZMANN INSTITUTE OF SCIENCE 

Organization address
address: HERZL STREET 234
city: REHOVOT
postcode: 7610001
website: www.weizmann.ac.il

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 Israel [IL]
 Total cost 2˙000˙000 €
 EC max contribution 2˙000˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2018-COG
 Funding Scheme ERC-COG
 Starting year 2019
 Duration (year-month-day) from 2019-05-01   to  2024-04-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    WEIZMANN INSTITUTE OF SCIENCE IL (REHOVOT) coordinator 2˙000˙000.00

Map

 Project objective

Almost 100 years ago, Warburg described a metabolic change in energy flux that occurs during carcinogenesis. Since then, multiple studies have demonstrated how anabolic synthesis of macromolecules can be altered to support cancer cell progression. Yet, the potential effect of altered catabolic degradation of macromolecules on tumour carcinogenesis has been much less studied.

The urea cycle (UC) is the main catabolic pathway by which mammals excrete waste nitrogen. Although the complete UC pathway is liver-specific, most tissues express different combinations of UC enzymes according to the cellular needs. Surprisingly, we find that changes in expression of UC components causing UC dysregulation, (UCD) is a global phenomenon in cancer, metabolically augmenting net nitrogen usage for the synthesis of macromolecules by reducing nitrogen waste. This metabolic alteration is associated with poor patient prognosis. Thus, we hypothesise that UCD provides a major metabolic advantage to multiple aspects of carcinogenesis and as such, leads to specific, identifiable genomic and biochemical signatures, with implications for cancer diagnosis and therapy.

To pursue our hypothesis, we will incorporate state-of-the-art comparative genomic, peptidomic, metabolomic, and molecular approaches to explore this scientific “blind spot” of nitrogen metabolism in carcinogenesis. We will investigate how UCD causally affects carcinogenesis, by characterising tumour-specific functions of UC enzymes (Aim I), correlating tumour phenotypes with systemic biomarkers (Aim II), and testing the treatment efficacy of drug combinations targeting UCD in cancers (Aim III).

Our proposal, strengthened by my training as a physician scientist, harbours considerable potential for translational diagnostic and therapeutic utility of our findings, enabling us to i) identify new diagnostic biomarkers for monitoring cancer initiation and progression and ii) predict and enhance the therapeutic response.

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

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