Objective
The link between inflammation and cancer is now established, yet the underlying molecular mechanisms are unresolved. As tumors progress, they modulate inflammatory cells towards a pro-tumorigenic phenotype. We have shown that inflammatory cells reciprocate by sculpting the parenchymal epithelial cells. I hypothesize that these reciprocal interactions lie at the heart of the link between inflammation and cancer.
Hepatocellular carcinoma (HCC), one of the deadliest tumors, is a prototype of inflammation induced cancer. My team will employ a twofold strategy to analyze the changes occuring in inflammatory cells before and after tumors emerge, based on preliminary findings showing that changes in inflammatory cells precede tumorigenesis. First, we will perform comprehensive mapping of the changing inflammatory microenvironment in a mouse model of inflammation induced HCC. We will employ genetic manipulation strategies, coupled to cell isolation techniques to delineate the molecular cues that mediate these changes and then will analyze the functional role of key mediators of these processes in HCC. Microfluidics approaches will give us a highthroughput quantitative view of these heterotypic interactions. The same approaches will be harnessed to identify the interactions that form the liver stem cell niche which dramatically expands in states of chronic inflammation. Second, drawing on our finding that a recurring tumor amplicon drives HCC progression by modulating the microenvironment, we will work towards identifying additional similar amplicons to define additional key effectors of the microenvironment.
Of special importance, heterotypic cell interactions that play key roles in both cancer initiation and progression, present ideal therapeutic targets, which are easily accessible and less amenable to mutational selection. Furthermore, the results of our experiments could also have far reaching implications in other inflammatory states and different types of cancer.
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.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- natural sciencesphysical sciencesclassical mechanicsfluid mechanicsmicrofluidics
- medical and health sciencesclinical medicineoncologyliver cancer
- medical and health scienceshealth sciencesinfectious diseases
- medical and health sciencesmedical biotechnologygenetic engineering
- medical and health sciencesmedical biotechnologycells technologiesstem cells
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Call for proposal
ERC-2011-StG_20101109
See other projects for this call
Funding Scheme
ERC-SG - ERC Starting GrantHost institution
91904 Jerusalem
Israel