Research focus
Peter Carmeliet’s laboratory focuses on one central topic ”Angiogenesis”, the growth of new blood vessels, in health and disease. Abnormal blood vessel growth, excessive or insufficient, contributes to multiple disorders, including cardiovascular disease, diabetes, cancer, age-related blindness, stroke, etc. Our ambition is to develop therapeutic concepts and, if possible, innovative anti-angiogenic treatments.
Latest findings indicate that the efficacy of current anti-angiogenic therapy (targeting VEGF) in cancer is limited by intrinsic refractoriness and acquired drug resistance. There is thus an urgent medical need to improve clinical anti-angiogenic therapy. To remedy this problem, Peter Carmeliet’s team uses a fundamentally distinct approach and pioneered the study of endothelial cell (EC) metabolism during angiogenesis, hypothesizing that targeting the metabolic “engine” of ECs would paralyze blood vessel growth and normalize tumor vessels. The role of several key metabolic targets in endothelial cell biology and tumor angiogenesis are currently studied.
The Carmeliet lab is also interested in unraveling the molecular basis of EC dysfunction and EC regeneration. EC dysfunction is of utmost importance in diseases such as diabetes, metabolic syndrome, etc., as it is a key determinant of cardiovascular morbidity and mortality, even when glycemia levels are under control. In fact, when becoming dysfunctional, the endothelium contributes to more (cardiovascular) diseases than any other cell type.
REVERSE EC METABOLIC PROFILING
Since little was known about EC metabolism, we started by selecting a particular metabolic target and studying the consequences of its over- or underexpression in ECs in vitro and in vivo on vessel sprouting (genotype-to-phenotype), termed “reverse metabolomics”:
PFKFB3: We showed that ECs are glycolysis-addicted (Cell 2013) and that partial, transient inhibition of glycolysis (by blockade of the glycolytic activator PFKFB3) sufficed to inhibit pathological angiogenesis without causing systemic effects (Cell Metab 2014). We also showed that low dose pharmacological PFKFB3 blockade induces tumor vessel normalization (TVN) and increases delivery and efficacy of chemotherapy (Cancer Cell 2016).
CPT1a: We reported that ECs (unlike cancer cells) use fatty acid (FA)-derived carbons in CPT1a-driven fatty acid oxidation (FAO) for de novo dNTP synthesis during EC proliferation, and that CPT1a blockade inhibits pathological angiogenesis (Nature 2015). We also showed that differentiation of venous to lymphatic ECs relies on the use of FA-derived acetyl-CoA as a signaling metabolite for epigenetic reprogramming of the differentiation switch (Nature 2016). Blockade of CPT1a inhibits pathological lymphatic growth, while replenishing acetyl-CoA levels by supplementing acetate rescues this process in vivo (Nature 2016). The Carmeliet lab has data (unpublished), showing that metabolite treatment (ketogenic diet) improves incurable lymphedema by stimulating lymphatic vessel growth, and is engaging in a clinical Phase II trial to test this in patients. In addition, the lab has data that metabolite treatment protects ECs against dysfunction (Cell Metabolism, in revision).
FORWARD EC METABOLIC PROFILING
Already for a few years, we are performing the novel research line of “forward metabolomics” (phenotype-to-genotype) by isolating ECs from mice and patients with disease (cancer, diabetes, etc.), and by using state of the art approaches, we are performing multi-omics profiling to identify metabolic targets that co-determine perturbed angiogenesis (such as in cancer or ocular disease) or EC dysfunction (causing cardiovascular disease in diabetics and neurological/neurodegenerative pathologies).
BIOMEXTM: We developed an in-house, user-friendly, bioinformatics platform for comprehensive analysis of transcriptomics / metabolomics / proteomic data to identify biomarker signatures (predictive diagnostic) and to discover new metabolic targets (theranostics).
Genome-scale metabolic modeling (GEM): Metabolism is hard-wired and therefore suited for computational modeling. GEMs allow prediction of metabolic targets determining ATP production, biomass synthesis, etc. We tailored a generic GEM to ECs by incorporating in-house generated bulk multi-omics data, and use it to identify novel metabolic targets, which we validate experimentally.
The combined approach of BIOMEX and GEM considerably increase the discovery power in our search for novel metabolic targets.
TRANSLATIONAL AIMS
We aim to set-up a spin-off company, theranostics platform, focusing on two fields: ‘Therapy’ and ‘Diagnostics’:
Drug discovery platform: Key EC metabolic targets, identified in prior work by the Carmeliet lab, are subject to development of inhibitors against metabolic targets and early pharmacological validation. These targets will be the proprietary drug pipeline for further drug discovery by the company for tumor vessel normalization in cancer therapy. The Carmeliet lab, together with VIB drug discovery, aims to (i) screen several libraries for small molecule chemical compounds inhibiting metabolic targets and (ii) develop lead-to-hit compounds via medicinal chemistry in order to generate interest at pharmaceutical companies for further drug development and clinical translation.
Metabolic target and biomarker discovery: The bioinformatics software platform (BIOMEX), will be further developed for improved discovery of co-blockade metabolic targets and metabolite biomarker identification (theranostics). We will utilize this platform to predict novel therapeutic metabolic targets in cancer to overcome therapy resistance, and to identify metabolic biomarker signatures that predict chemotherapy and immunotherapy response in different cancer patients.
> video on basic research on the importance of metabolism in cancer & angiogenesis - Peter Carmeliet
- ©VIB, 2015
News
04/03/2019 - Each year, the EU launches calls for postdoc research fellowships through the Marie Sklodowksa-Curie Actions. Fellowships provided through these actions support researchers regardless of age & nationality.
30/08/2018 - A multi-disciplinary team of scientists, led by Peter Carmeliet (VIB-KU Leuven) has made several breakthrough discoveries concerning the metabolism of the individual building blocks of blood vessels - the so-called endothelial cells.
24/04/2018 - Peter Carmeliet from the VIB-KU Leuven Center for Cancer Biology has been awarded the prestigious 2018 Heineken Prize for Medicine for his important and fundamental research into blood vessel formation.
05/04/2018 - Peter Carmeliet (VIB-KU Leuven Center for Cancer Biology) was honored with the 46th annual ARC Foundation Leopold Griffuel Award, a prize of EUR 150,000.
08/06/2017 - Peter Carmeliet of VIB-KU Leuven Center for Cancer Biology was appointed as an international member of the Royal Netherlands Academy of Sciences (KNAW). It is very exceptional that foreign researchers are allowed to join this network.
23/03/2017 - Prof. Peter Carmeliet (VIB-KU Leuven) is awarded an Advanced Grant. To qualify, a scientist has to be able to prove exceptional leadership and a solid track record of significant research achievements over at least 10 years.
26/12/2016 - An international team of researchers, led by Peter Carmeliet (VIB-KU Leuven), discovered how a shift to increased fat utilization is required for the development and growth of these ‘roads’, termed lymphatic vessels – a special kind of blood vessels.
23/11/2016 - In a cross-domain study directed by professor Peter Carmeliet (VIB – KU Leuven), researchers discovered unexpected cells in the protective membranes that enclose the brain, the so called meninges.
17/11/2016 - Researchers at VIB and KU Leuven have found a novel way to normalize the dysfunctional blood vessels that are typical for tumors. Those vessels play a pivotal role in cancer metastasis.
07/01/2016 - Research led by prof. Peter Carmeliet and dr. Annelies Quaegebeur (VIB/KU Leuven) indicates that inhibition of PHD1 offers protection against stroke, via an unexpected mechanism, raising hope for future stroke treatment.
30/07/2015 - Scientists at VIB and KU Leuven have shown that reducing the expression of the PHD2 oxygen sensor impairs the ability of breast cancers to metastasize (spread) to other parts of the body.
22/07/2015 - With the appointment of seven barons, three baronesses, three knights and an earl, King Philip has raised fourteen people into peerage.
10/07/2015 - Sandra Schoors, Ulrike Bruning, Sarah-Maria Fendt and Peter Carmeliet (VIB Vesalius Research Center, KU Leuven) have discovered, contrary to all expectations, that fatty acid breakdown is essential for the proliferation of endothelial cells.
01/07/2015 - From September 8 – 10, 2015 VIB will host the interdisciplinary meeting on “Metabolism in Cancer and Stromal Cells” in Leuven.
26/06/2015 - Oncurious NV, an oncology company focused on the development of innovative medicines for the treatment of pediatric tumors, today announces the appointment of Prof. Dr Peter Carmeliet as its Chief Scientific Strategy Advisor.
01/04/2015 - Peter Carmeliet and Sarah-Maria Fendt (VIB/ KU Leuven) have discovered a new strategy to counteract blood vessel formation, based on their research which indicates that fatty acid breakdown is essential in the creation of new blood vessels.
09/07/2014 - New therapeutic avenues for diabetes, inflammatory conditions & cancer.
03/02/2011 - The Fournier-Majoie Foundation for Innovation (FFMI) has awarded Max Mazzone of VIB-K.U.Leuven a grant for research into a new method of early detection of colon cancer.
18/11/2010 - VIB researchers Peter Carmeliet and Bart De Strooper have both been awarded Advanced Grants from the European Research Council. ERC Advanced Grants are the most prestigious European research grants, spanning a period of 5 years.
01/07/2010 - Oxford BioMedica and VIB-K.U.Leuven announce an award by the UK MND Association of a research grant to support the further development for the treatment of ALS with gene therapy.
28/06/2010 - Two of the five FWO prizes of EUR 100,000 were awarded to VIB scientists, namely Dirk Inzé (VIB-UGent) and Peter Carmeliet (VIB-K.U.Leuven).
10/02/2010 - The European Medicines Agency (EMEA) has recognized a Leuven lab’s candidate medicine to combat the neurodegenerative disease ALS (Amyotrophic Lateral Sclerosis) as a 'weesgeneesmiddel' (‘orphan medicine’).
08/01/2010 - His pioneering research on heart and vascular diseases and thrombosis has earned Peter Carmeliet the prestigious Ernst Jung Medical Award, one of the highest European prizes for biomedical research.
01/12/2008 - Permission has been granted to start the first safety and tolerability trial on patients for a remedy for ALS. ALS is an incurable, paralyzing neurodegenerative disorder that strikes 5 persons in every 100,000.
29/10/2007 - VIB scientists connected to the Katholieke Universiteit Leuven, in collaboration with the Flemish biotech company ThromboGenics, have been studying the anti-cancer action of anti-PLGF.
16/08/2005 -
28/11/2004 - Research shows that rats with a severe form of ALS live longer following the administration of the VEGF protein as a remedy. These results open up new possibilities for the use of VEGF in the treatment of ALS.
28/10/2004 - VIB researchers have shown that new blood vessels do not grow in random directions, but that they are guided by specific signal molecules. This is a major step in the development of new targeted forms of therapeutic angiogenesis.
19/08/2004 - Belgian researchers from VIB (the Flanders Interuniversity Institute for Biotechnology), lead by Prof. Peter Carmeliet (K.U.Leuven) already indicated the importance of the VEGF growth factor in this illness.
26/05/2004 - Researchers from VIB (the Flanders Interuniversity Institute for Biotechnology), lead by Prof. Peter Carmeliet (K.U.Leuven) already indicated the importance of the VEGF protein in this illness, on the basis of genetic studies.