Skip to main content
Go to the home page of the European Commission (opens in new window)
English English
CORDIS - EU research results
CORDIS

Origin of genomic instability: Understanding the biological influence of inflammation in the initiation of pancreatic tumorigenesis

Project description

The role of inflammation in cancer

It has long been speculated that chronic inflammation may serve as a trigger for cancer onset. Recent evidence indicates that the transforming growth factor beta (TGF-b) cytokine, observed in inflammatory states, negatively impacts genomic integrity by activating epithelial-to-mesenchymal-transition (EMT). This transient epigenetic reprogramming, key during tumour invasion and metastasis, leads to chromosomal instability. The EU-funded Onco-inflammation project focuses on pancreatic ductal adenocarcinoma and aims to delineate the inflammatory mechanisms responsible for inducing genomic instability. Project researchers hypothesise that cell reprogramming is a key intermediate in the creation of genomic instability in pancreatic tissue, similar to what is observed under EMT. Results will provide fundamental knowledge on the association between inflammation and cancer.

Objective

Inflammation is suspected to be the first step leading to cancer due to alcohol consumption or tobacco smoking between others. Little is known of how inflammation triggers genetic changes leading to tumorigenesis. Recently, I show that TGFb, a cytokine present during inflammation, is able to generate aneuploidy, polyploidy and plausible chromosomal rearrangements in breast cells. Such effects were mediated through the induction of the epigenetic reprogramming EMT. In view to understand how inflammatory signaling can affect the genome integrity, I design the project Onco-Inflammation, to study one of the most lethal cancer, the pancreatic ductal adenocarcinoma (PDAC), where therapeutic options are greatly limited. Using several mice models of pancreatitis, we will follow the establishment of genomic insults, and in particular focusing in whole genome doubling, nuclear envelope disruption and micronuclei. I will evaluate the genetic diversity present under pancreatitis and weigh the roles of the epigenetic re-programming Acinar-Dutual-Metaplasia as well as the oncogene KRAS, using high-resolution 3D imaging, as well as single cell CNV analysis (Aim1). I will also study the common pathways activated in newly aneuploid cells, in view to find some specific therapeutic target. (Aim2). Several pathways will be tested in an attempt to block cancer initiation and progression. Results will be tested and validated using human samples (Aim 3). At the Host Institution, I will greatly benefit and learn from the scientific guidance from my supervisor, expert in pancreas biology as well as experts in mitosis, genetic instability and bioinformatics. MSCA-IF will be instrumental to develop this initial hypothesis into deeper biological understanding the inflammation and cell plasticity’s roles on genomic instability and represent a crucial support to transition into an independent academic career.

Fields of science (EuroSciVoc)

CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.

You need to log in or register to use this function

Keywords

Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)

Programme(s)

Multi-annual funding programmes that define the EU’s priorities for research and innovation.

Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

See all projects funded under this funding scheme

Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2020

See all projects funded under this call

Coordinator

FUNDACION PUBLICA ANDALUZA PROGRESO Y SALUD M.P.
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 172 932,48
Address
AVENIDA AMERICO VESPUCIO 15 EDIF S2
41092 Sevilla
Spain

See on map

Region
Sur Andalucía Sevilla
Activity type
Research Organisations
Links
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 172 932,48
My booklet 0 0