Objective
During my post-doctoral studies, I have shown that sugarcoating of proteins, “N-glycosylation” specifically, is essential for the development and a potential therapeutic target in the blood cancer myeloproliferative neoplasms. Here, I show that differential expression of three enzymes that are key to protein sugar coating are strong novel prognostic factors in the blood cancer acute myeloid leukemia (AML). Specifically, these enzymes remove or add glucose molecules of the N-glycan sugar tree. Removal of the outer glucoses is essential for retaining N-glycoproteins within the endoplasmic reticulum (ER) and unprocessed N-glycans contain a high number of mannose sugars. I hypothesize that unprocessed N-glycoproteins such as growth receptors and drug removal pumps escape the ER and are expressed on the cell surface at a higher level due to abnormal expression of genes implicated in sugar coating (ALG10B, MOGS and PRKCSH). This in turn contributes to AML development and poor outcome. To proof my hypothesis, I will decipher the role of key enzymes in N-glycan glucose addition and removal to myeloid oncogenesis (aim 1A) and drug resistance (aim 1B) using colony forming unit assays and cell lines that express ALG10B or lack MOGS/PRKCSH (CRISPR-Cas9 knockout). Additionally, I will assess mannose abundance and targetability on primary AML versus healthy control bone marrow samples (aim 2A), and map N-glycan structures using recently developed high-throughput mass spectrometry and analyses techniques (aim 2B). I will correlate structural N-glycan profiles with expression of N-glycan processing enzymes assessed through RNA-sequencing to create a full picture of N-glycosylation aberrancies in AML. This study will decipher the molecular mechanisms underlying aberrant N-glycosylation in AML and provide anchor points for novel AML therapies. This is important, because the current 5-year overall survival rate of AML is only ~30% so therapy improvements are highly warranted.
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.
- engineering and technology materials engineering coating and films
- medical and health sciences clinical medicine oncology leukemia
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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)
MAIN PROGRAMME
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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.
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.
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
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2021-PF-01
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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.
6525 GA NIJMEGEN
Netherlands
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.