Stellar cross-domain insights from Peter Carmeliet and his team

20 March 2017

Researchers from the lab of Peter Carmeliet (VIB-KU Leuven Center for Cancer Biology) made an unexpected discovery: the meninges, previously thought to be simply a protective membrane on the outer surface of the brain, actually contains cells that give rise to neurons. Before this finding, scientists thought that these types of cells were only produced by the body during development. The research was published in Cell Stem Cell and gives rise to interesting leads for further investigation.

In another study, which was published in Nature, Peter’s team investigated the mechanisms behind the development of lymphatic vessels, discovering that an enzyme that regulates lymphatic cells’ use of fatty acids is critical to the process. Since tumors and other diseases are associated with increased levels of lymphangiogenesis – the creation of new lymphatic vessels – this finding could lead to new therapies that block the effects of this enzyme.

To find out a little bit more about the successful productivity of his lab, take a look behind the scenes of projects and explore what the future might have in store for this research, we asked Peter Carmeliet to answer a few questions.

Could this new source of neural progenitor cells in the meninges provide opportunities to treat disease or injury of the brain?
Peter: “An intriguing question indeed. To answer it, we still have more work to do. For example, it’s necessary to better understand the molecular mechanisms that cause these cells to be activated, differentiated and moved. We also need to investigate the meninges of the spinal cord, to see if it contains neural progenitors. Can these cells be transplanted in vivo? Can they be induced to become different types of neurons in vivo? These are all interesting tracks for future research.”

The Cell Stem Cell paper is the first publication using cutting-edge single cell RNA sequencing in VIB. What are the advantages of this technology?
Peter: “Most importantly, this method allows us to identify very tiny cell subgroups within large populations of cells. The cells we were targeting make up only a tiny fraction of the cells in the meninges, and without single cell RNA sequencing, we would have never been able to discover and identify them. Though mapping out the single cell gene expression landscape is the first necessary step, scaling single-cell genomics from
phenomenology to mechanism and function is the next challenge.”

Regarding your paper on lymphangiogenesis, what triggered you to do research outside the main interests of the host lab?
Peter: “Nothing was known about the metabolism – or the rate of consumption of fatty acids – of lymphatic endothelial cells (LECs). In fact, since LECs are present in environments with lower oxygen levels, we assumed that their metabolisms would be anaerobic – and it’s exactly the opposite. They rely on these fatty acids and aerobic pathways to multiply and differentiate. These findings strengthen the idea that targeting the metabolism of vascular cells may be an important translational path.”

2016 was a hugely productive year for you – over 30 publications in leading academic journals, including the following top tier publications: 1 Cancer Cell, 4 Natures, 1 Science, 1 Cell Stem Cell, 4 Cell Metabolisms, 2 Cell Reports, 1 Science Immunol, 2 Nature Comm, 1 Ann Rev Physiol, 1 Nat Rev Neurol, 1 editorial in Dev Cell and 1 Cell Metabolism, and numerous other papers. Do these papers have a common focus?
Peter: “We’ve focused on cellular metabolism of vascular cells in the last several years, although we’ve collaborated on studies involving bone cells, immune cells and others. About 7 years ago, we chose to target endothelial cell metabolism, which had been previously overlooked. As a result, we completely restructured our lab and set up a metabolomics core facility, attracted new talent, etc. All this effort is paying off hugely in papers that explore uncharted territory across domains.”

And what is the scientific verus the social relevance of these papers?
Peter: “Our studies provide unprecedented insight into how vessels are formed and shine light on metabolic pathways that control vessel formation in health and disease. Since there are over 4,000 metabolic enzymes and transporters, targeting them is a rich resource for drug development.”

How do you manage to oversee all those projects while publishing papers simultaneously?
Peter: “I sometimes indeed wonder how to do this best, but I don’t feel overwhelmed. I’m too fascinated. I’m also lucky to be working with a wonderful team of excellent, knowledgeable, motivated, focused, time-management efficient and well-organized staff, senior colleagues, junior scientists and lab technicians to whom I delegate a lot, and whom I involve in the work at all levels - three brains are simply smarter than one alone. This productivity is a team effort, and 2016 was a vintage year.”

The research topics you choose are far from obvious. How important is out-of-the-box thinking and risk-taking in research, and where do you find the funds for it?
Peter: “Asking ‘high-gain’ questions is always risky. What matters is that you judge the risk and weigh the gain in order to make an informed decision to move forward relentlessly. These decisions require long-term commitment before any success can happen. Focused minds, a willingness to readjust strategies and find creative solutions, careful reconsideration, perseverance and strong motivation render the risk less risky. Also, the award of mining uncharted territory offers strong perspectives to embark on risky journeys. We keep
an eye open for new opportunities, and support talent regardless of education, experience or seniority – this always pays off.

High profile research requires large funds, and like everybody else, we spend a lot of time writing grants and fellowships to perform innovative research (with rejected grants being equally part of our daily life experience). But we also pay great attention to careful budgeting, and with carefulconsideration, plenty of creativity and mutual discussions, budgets are reduced and the project completed at much higher efficiency.”

Publications
Wong et al., Nature 2016
Bifari et al., Cell Stem Cell 2016
Cantelmo, et al., Cancer Cell 2016​



Peter Carmeliet (VIB-KU Leuven)
©VIB-Ine Dehandschutter