Peter Carmeliet
The Neuro-Vascular Link in Health and Disease
VIB Vesalius Research Center, K.U.Leuven

Peter Carmeliet MD: Univ. of Leuven, Leuven, Belgium, '84 PhD: Univ. of Leuven, Leuven, Belgium, '89 Associated Res. Scientist: Harvard Medical School, Boston, USA, '89-'90 Associated Res. Scientist: Whitehead Institute, MIT, Cambridge, USA, '90-'92 VIB Group leader since 1996 Adjunct Director, Dept. of Transgene Technology and Gene Therapy (now VRC) since 2001

e-mail phone +32 16 34 61 42 ADDRESS

Current team members
Group leader: Peter Carmeliet
Staff scientist: Mieke Dewerchin
Expert: Lieve Moons
Postdoctoral scientists: Behzad Kharabi, Carmen Ruiz de Almodovar Egea, Christian Lange, Françoise Bruyère, Hilde Laeremans, Inmaculada Segura-Vitutia, Katrien De Bock, Sandra Cauwenberghs, Stefan Vinckier, Tobias Langenberg
Ph.D. Students: Anna Kuchnio, Annelies Quaegebeur, Cathy Coulon, Ellen Knevels, Els Janssens, Ian Buysschaert, Maria Georgiadou, Sara Van de Veire, Wouter Vandevelde
Support personnel: Agnes Truyens, An Carton, An Van Nuffelen, Ann Manderveld, Anneke Bouché, Anne-Marie Geyskens, Annemie Van Den Broeck, Arnold Van Den Eynde, Bieke Tembuyser, Bjorn Vanwetswinkel, David Verbeek, Els Gils, Ester Van Dyck, Hanne Bellens, Hélène Hagens, Inge Betz, Joris Souffreau, Kathleen Brepoels, Katie Van Geyte, Kelly Taes, Kevin Feyen, Kristel Peeters, Leen Notebaert, Lucica Goddé, Maria De Mol, Martine Nijs, Naima Dai, Odessa Van Goethem, Paolo Carai, Peggy Vanwesemael, Sabine Wyns, Sandra Jansen, Sarah Verbylen, Siegfried Verstraeten, Staf Geuens, Wendy Martens

Keywords
angiogenesis - lymphangiogenesis - neurobiology - neurodegeneration

Science
Global research efforts have yielded the sequence of the entire human genome. Even though ‘only’ ~ 35,000 genes have been identified, many of these genes have numerous transcripts encoding several proteins, which can be further modified post-translationally. Consequently, over 100,000 proteins are estimated to determine our health and diseases. One of the great challenges in biomedical research for the next decade is now to unravel the function and interaction of these disease candidate genes and to determine how their function is influenced by modifier genes and environmental factors. This would allow us to understand the pathogenetic role of these genes in common medically important disorders, to identify novel diagnostic tools and to develop safer and more effective treatments. We use the following genetic techniques to perform the proposed ‘functional genomics’ studies: (i) gene-targeting in the mouse; (ii) genetic manipulatino of small animal models (zebrafish, tadpoles); and (iii) human genetics. While each of these techniques is instrumental itself, together, their combined used provides a powerful approach. Mouse genetics: By studying biological responses in genetically manipulated mice overexpressing defined genes, lacking defined genes or carrying mutagenized genes, it is possible to achieve novel insights in the role and relevance of genes in vivo. The transgenic animals thus obtained may represent models of human disease, which then can be used for the evaluation of new genetic or other therapeutic strategies. Furthermore, the gene-deficient or mutant mice and the tissues or cell lines derived thereof, provide unique material for gene profiling in order to identify and characterize novel genes involved in specific processes. Alternatively, the discovery of unexpected novel phenotypes associated with a specific knockout or mutation may implicate a previously unrecognized involvement of a particular gene in a defined disorder. Zebrafish genetics: Most of the common diseases are complex and multifactorial in nature. Due to the laborintensive and time-consuming character of mouse transgene technology, the mouse model is less suited for simultaneous analysis of gene products interacting with each other, and limited to the analysis of a restricted number of genes. Semi-high throughput analysis of genetic pathways or gene-interactions can, however, be performed in the zebrafish. Indeed, due to its small size, easy breeding, short life-span, embryo transparancy, and amenability for morpholino knock-down of gene expression, the zebrafish constitutes a unique and powerful model. Human genetics: It is essential to confirm that the findings obtained in the mouse and zebrafish genetics are valuable for human health. This can, in part, be achieved by performing association or mutational studies in affected humans. In addition, we will use genetic linkage, in combination with zebrafish genetics, to positionally clone and identify novel disease candidate genes.

Our research is focused onto two major medical health problems: cardiovascular and neurological. Cardiovascular: We study the molecular basis of cardiovascular disorders including myocardial infarction, stroke, atherosclerosis, thrombosis, aneurysms, restenosis, heart failure, arrhythmias, etc. Particularly, we study the role of fibrinolytic and matrix metalloproteinases and coagulation proteinases. A major focus has been on angiogenesis (formation of blood vessels), which is not only essential for development but also for more than 70 disorders (cancer, ischemia, etc). In particular, we study the role of VEGF, hypoxia-signaling and oxygen sensing in angiogenic disorders and the molecular mechanisms of lymphangiogenesis (formation of lymphatic vessels – critical for tumor metastasis) and stem cell-mediated vessel growth. Neurological: Blood vessels also affect the nervous system. Through gene-targeting experiments, we discovered a novel and unexpected role of VEGF in motor neuron degeneration. Ongoing studies are focused on unraveling the mechanisms of how VEGF affects motor neuron survival, confirming the relevance for human disease (association studies), and developing therapeutic strategies. In addition, we study the molecular signals responsible for self-renewal and multipotentiality of neural stem cells, and will test whether these molecules can be employed for neural tissue regeneration in CNS injury, ischemia or degeneration

To optimize the efficiency, increase the productivity, promote interdisciplinary research, facilitate training and education of junior scientists, streamline transfer of knowledge and expertise, Peter Carmeliet has organized the technical resources around an infrastructure of expert core facilities.

Press Releases
See also press release (01/07/2010): Oxford Biomedica and VIB-K.U.Leuven announce collaborative research project to develop MoNuDin® for treatment of ALS

See also press release (28/06/2010): International Recognition for Top VIB Research - VIB scientists land two of five FWO Prizes of Excellence

See also press release (10/02/2010): Development of Leuven’s candidate medicine against nerve disease ALS moves into higher gear

See also press release (08/01/2010): Research on heart and vascular diseases earns Peter Carmeliet of VIB and K.U.Leuven the Ernst Jung Medical Award 2010

See also press release (01/12/2008): First trial in patients with a potential treatment of the incurable ALS muscle disease

See also press release (31/01/2008): Progress toward an alternative for EPO: Gas6 offers remedy where EPO fails today - based on a publication in The Journal of Clinical Investigation (Angelillo-Scherrer et al., The Journal of Clinical Investigation, 2008).

See also press release (06/01/2008): Important medical breakthrough for organ transplants and cardiovascular diseases based on a publication in Nature Genetics (Aragonés et al., 2008).

See also press release (01/11/2007): On the road to a new cancer therapy - starving the tumor - based on a publication in Cell (Fischer et al., Cell, 2007). Only 2 weeks after publication, this paper has reached the  number 1 position of the prestigious journal CELL’s Top20 list, based on the number of downloads.

Interview
Read a recent interview with Peter Carmeliet by Thomson ISI in ISI Essential Science Indicators.

Research in focus
Read about the research of Peter Carmeliet in VIB research in focus.

3D animation
Cancer strikes one out of four persons. Will VIB research lead to an efficient treatment? Click here and discover it yourself in the 3D animation.

Go to the  Department's own website for more details.

Mazzone M, Dettori D, Leite de Oliveira R, Loges S, Schmidt T, Jonckx B, Tian Y, Lanahan A, Pollard P, Ruiz de Almodovar C, De Smet F, Vinckier S, Aragonés J, Debackere K, Luttun A, Wyns S, Jordan B, Pisacane A, Gallez B, Lampugnani M, Dejana E, Simons M, Ratcliffe P, Maxwell P, Carmeliet P
Heterozygous deficiency of PHD2 restores tumor oxygenation and inhibits metastasis via endothelial normalization
CELL 136, 839-51, 2009



Fischer C, Mazzone M, Jonckx B, Carmeliet P
FLT1 and its ligands VEGFB and PlGF: drug targets for anti-angiogenic therapy?
NAT REV CANCER 8, 942-56, 2008



Fischer C, Jonckx B, Mazzone M, Zacchigna S, Loges S, Pattarini L, Chorianopoulos E, Liesenborghs L, Koch M, De Mol M, Autiero M, Wyns S, Plaisance S, Moons G, Van Rooijen N, Giacca M, Stassen J, Dewerchin M, Collen D, Carmeliet P
Anti-PlGF Inhibits Growth of VEGF(R)-Inhibitor-Resistant Tumors without Affecting Healthy Vessels
CELL 131, 463-75, 2007



Storkebaum E, Lambrechts D, Dewerchin M, Moreno Murciano M, Appelmans S, Wang I, Van Damme P, Rutten B, Man W, De Mol M, Wyns S, Manka D, Vermeulen K, Van Den Bosch L, Mertens N, Schmitz C, Robberecht W, Conway E, Collen D, Moons G, Carmeliet P
Treatment of motoneuron degeneration by intracerebroventricular delivery of VEGF in a rat model of ALS
NAT NEUROSCI 8, 85-92, 2005



Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens M, Gertsenstein M, Fahrig M, Vandenhoeck A, Harpal K, Eberhardt C, Declercq C, Pawling J, Moons G, Collen D, Risau W, Nagy A
Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele
NATURE 380, 435-9, 1996

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