Project description
Suppressor genes in endothelial cells for effective immunotherapy
Cancer is a major cause of death, with some types resistant to traditional immunotherapy (IT). Endothelial cells (ECs) contribute to this resistance through their immunosuppressive properties. Targeting immunosuppressive genes in tumour ECs may enhance anti-tumour responses and improve IT effectiveness. With the support of the Marie Skłodowska-Curie Actions programme, the DETECTIVE project aims to identify novel immune suppressor (IMMUSUP) genes in tumour ECs to enhance anti-tumour immune responses. Focusing on poorly annotated ‘mystery genes’ that comprise one-third of the mammalian coding genome, the project will use artificial intelligence and machine learning to prioritise EC IMMUSUP genes. This research seeks to identify new drug targets in tumour ECs to enable more effective immunotherapy.
Objective
Despite significant medical advancements, cancer remains a major cause of mortality worldwide, and several cancer types still lack efficient therapy, in part due to resistance to traditional immunotherapy (IT). Endothelial cells (ECs) present an important yet overlooked modulator of tumor immunity, possessing an immunosuppressive nature, and proposed to contribute to IT resistance. Studies of the host lab indeed identified immunomodulatory features in EC subsets (coined IMECs). My central hypothesis is that targeting immunosuppressive (IMMUSUP) genes in tumor ECs may promote anti-tumor immune reaction to overcome resistance and improve the efficacy of traditional IT. The aim of this work is to identify novel, IMMUSUP genes expressed by tumor ECs and assess the potential of targeting these genes in vivo to promote anti-tumor immune response. I will explore in particular “mystery genes” (with poor functional annotation, ca 1/3 of the mammalian coding genome and an unexplored resource of potential targets) to maximize the identification of novel IMMUSUP genes beyond the currently used targets in traditional IT. Thus, I will (i) identify and prioritize EC IMMUSUP genes using artificial intelligence/machine learning approaches and (ii) in silico bioinformatics coupled to a mystery-genome wide siRNA screen to reveal IMMUSUP activity; (iii) confirm IMMUSUP targets via lipid nanoparticle-based siRNA delivery to generate EC-specific knockdown mice in models of lung, esophageal, and liver cancer; and (iv) determine the Mode of Action of the most promising targets using multidisciplinary approaches. My work will yield insights about previously unknown drug targets in tumor ECs, potentially paving the way for development of alternative IT with enhanced efficacy. My prior experience in immunology and bioinformatics combined with the host lab's expertise in EC (dys)function and single cell -'omics' technologies will ensure high quality execution of this project.
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.
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.
- medical and health sciences clinical medicine oncology liver cancer
- social sciences sociology demography mortality
- medical and health sciences basic medicine immunology immunotherapy
- natural sciences biological sciences genetics genomes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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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
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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.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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(opens in new window) HORIZON-MSCA-2023-PF-01
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9052 ZWIJNAARDE - GENT
Belgium
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