The lab: Carmeliet group
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.
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.
Other positions
IDIBAPS#4 – Mechanisms involved in strenuous exercise-induced atrial myocardial fibrosis
IC#4 – The role polyglutamylation in tauopathic neurodegeneration
IC#3 – Evaluation of the efficiency of immunotherapy by tracing ctDNA in metastatic NSCLC and triple-negative breast cancer patients
IC#2 – New targetable vulnerabilities for the treatment of chemoresistant breast and ovarian BRCA1/2-mutated tumors
IDIBAPS#3 – Mechanisms involved in vascular inflammation/remodeling in systemic vasculitis
IDIBAPS#2 – Mechanisms and therapies for Myeloma, amyloidosis, macroglobulinemia and other gammapathies
IDIBAPS#1 – Developing and investigating computing, machine learning and physiological modelling for understanding each individual heart towards personalised medicine
BRIC#6 – Tumour evolution, heterogeneity, and understanding of the mutational processes leading to aggressive disease
IC#1 – The role of RNASE1 in lung metastatic niche establishment by breast cancer cells
MDC#3 – Neuromuscular and Cardiovascular Cell Biology
MDC#2 – Molecular and cellular basis of behavior
MDC#1 – Host-microbiome factors in cardiovascular disease
NKI#1 – Epigenetic regulation in hormone-driven cancers and therapy resistance
VIB#8 – Mechanisms of inflammation and associated tissue damage in musculoskeletal diseases
VIB#7 – Endothelial immunosuppressive mystery genes for alternative immunotherapy: artificial intelligence-driven target discovery and validation
VIB#6 – Cellular metabolism and metabolic regulation in cancer metastasis
VIB#5 – Unraveling the molecular mechanisms of neuronal degeneration in motor neuron diseases
VIB#4 – Identification of universal biomarkers of metastatic melanoma in CTCs
VIB#3 – Basic mechanisms of Alzheimer’s disease and neurodegeneration
VIB#2 – Integrative genomics to underpinning somatic evolution, tumour heterogeneity, and treatment resistance
VIB#1 – Medical biotechnology to improve hepatocellular carcinoma diagnostics
BRIC#5 – The impact of severe maternal respiratory tract infections on fetal brain development and offspring behavior
