The lab: Carmeliet group

VIB

Lab's research themes:

Current anti-angiogenesis therapies (AATs), by targeting the pro-angiogenic factor VEGF, suffer resistance and insufficient efficacy. The Carmeliet lab explores opportunities to overcome these limitations and to improve AAT by focusing on endothelial cell metabolism, endothelial heterogeneity and in particular, endothelial immunity.

Recent projects, combining single-cell transcriptomics with bulk multi-omics (transcriptomics, (epi)-genomics, proteomics & metabolomics) revealed novel insights into endothelial cell metabolism and heterogeneity in health and disease that can help design novel AAT strategies. A major challenge of current medical research is to translate obtained high-profile insights into new medicine. We aspire to not only discover new therapeutic targets, but also to "bridge the valley of death" in order to improve drug development.

Merits of the lab:

The laboratory of Angiogenesis and Vascular Metabolism headed of Prof. Peter Carmeliet is one of the laboratories of the Center for Cancer Biology (CCB), a research department of VIB (Flanders Institute for Biotechnology) located in the Oncology Faculty at the KU Leuven (Leuven, Belgium).

The lab is closely embedded in the University hospital Gasthuisberg, and active collaborations with the Health Department of Aarhus Univeristy (Denmark) are running. We try to bridge the valley of death by functionally validating novel targets discovered via AI tools. Previous research from our lab have lead to the start up of several spin off companies (e.g. Montis Biosciences).

Why do we want medical doctors?

The group leader Peter Carmeliet is an MD in training. He currently hosts a large research group with a good balance of technical staff, PhD students, postdocs, visiting and staff scientists. People are selected based on their scientific merits and motivation, irrespective of gender, origin, nationality or background. Diversity in skills and expertise (novel technologies, computational skills, cell biology, animal models, etc.) is essential in the functioning of our lab, with many different research profiles contributing to the success of our research lines. Several research lines are translational/clinically oriented and involve MD scientists.

Country: Belgium
Supervisor: Peter Carmeliet
Research group website

The position

What’s the main purpose of our research?

Endothelial immunosuppressive mystery genes for alternative immunotherapy: artificial intelligence-driven target discovery and validation. We aim to obtain novel insights into an understudied endothelial cell (EC) subtype with immunomodulatory gene signatures, highly relevant for alternative immunotherapy development. For instance, in tumors, ECs are mainly immunosuppressive and a barrier for anti-tumor immune cells, while upregulation of immunostimulatory and pro-inflammatory genes in ECs may contribute to chronic inflammation.

How we will do it?

We will:

1) use an in-house developed artificial intelligence (AI)-based tool to identify truly novel immunosuppressive genes in the ‘mystery genome’ (1/3 of the genome that lacks functional annotation), a true goldmine for innovative target discovery;

2) directly validate in vivo the predicted immunosuppressive mystery genes by generating EC-selective knockout mice rapidly (days)/low cost using a new in-house developed transgenic REVOLT technology;

3) perform initial selectivity/toxicity assessment by elaborate (in silico) target expression analyses. All approaches are operational.

Why is this important?

The challenge anno 2022: There is a daunting need for new drugs, yet many research results do not reach clinical translation, partly because of:

(i) insufficient target discovery/validation; and (ii) suboptimal drug target selection (resulting in insufficient efficacy/safety). Academic research targets are often cherry-picked without another goal than gaining knowledge, and without considering upfront if they might become suitable drug targets. The immense investment in research and the poor yield/high cost of drug development begs for the revision of this model. In this project, we aspire to provide proof-of-concept for improved target discovery, selection & validation, focusing on the clinical need to improve cancer immunotherapy (IT).

Who is a good fit for the project?

A medical background in oncology or cardiovascular diseases is a plus – no specific technological background is required.

Cardiovascular diseases, oncology or immunology training are an added value but not mandatory.

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