A network of endothelial cells separates the circulating fluids, i.e., blood and lymph, from the internal tissue and organ environment in the human body. However, endothelial barrier function differs from one organ to another. With a foothold in both the United States and France, Anne Eichmann is fascinated by its versatility. She was recently awarded funding by the European Research Council (ERC Advanced Grant) to identify its key regulators: these will all create potential therapeutic targets to treat different diseases.
How did you start working on endothelial cells?
I embarked upon veterinary studies in Berlin, but decided to branch off into human biology. I thus started a new course in Israel, at the Weizmann Institute. That was where I first started working in the laboratory, and discovered my calling in research. I then went to France to study for my Ph.D., at the Institut d’embryologie du Collège de France, supervised by my mentor, Nicole Le Douarin. I ended up staying for more than 10 years! It was at the Collège de France that I led my first team and began working on endothelial cells, now the focus of my work. Vascular biology is a fascinating field. There are vast amounts of endothelial tissue in the body: it can cover a surface area in the adult human body equivalent to the size of a tennis court! Furthermore, endothelial cells play a central role in gas, immune mediator and nutrient exchanges between blood or lymph and organs.
There are said to be more than 80 diseases which affect the endothelial cells. Where does this diversity come from?
Endothelial cells form a barrier between the inside of blood or lymphatic vessels, and the tissues through which they pass. Now, although the constitution of endothelial tissue is generally identical wherever it is found in the body, its function can be very different, ranging from extremely porous to extremely tight. Faced with this diversity, the etiology of endothelial disorders is evidently equally diverse: these can include bacterial or viral infections, allergies (including respiratory allergies), inflammatory disease (psoriasis, Crohn’s disease, etc.), neurodegenerative disease and cancer. Despite the vast presence of this tissue in the body, its function is still unclear, which is a huge challenge. My ambition is to gain better insight into the cellular mechanisms and molecular factors which allow endothelial tissue to behave in such a diverse manner. I would also like to identify the associated physiopathological mechanisms, with the aim of defining new therapeutic approaches in the longer term.
What avenues of research are you hoping to develop as part of your ERC grant?
Our previous research mainly revealed the role of a growth factor, VEGF-A, in the neovascularization and impermeability of intestinal lymphatic vessels. The action of VEGF-A on intestinal lymphatic vessels is therefore thought to play a not insignificant role in obesity. More recently, we successfully modified the natural impermeability of the blood-brain barrier (BBB), by modifying the expression of genes coding for endothelial transmembrane proteins contributing to tight junctions. Based on this discovery, we can envisage targeting these proteins with specific monoclonal antibodies, with a view to blocking their function and allowing drugs temporarily to pass into central nervous system tissue. Lastly, we have described some of the mechanisms involved in lymphatic vessel porosity and chronic edema.
With the Breaking Barriers project, funded by the ERC, we would like to gain better insight into the mechanisms involved in the coordination of endothelial barrier function, and learn how these can be manipulated for therapeutic purposes. This research will be conducted using two extreme examples of the BBB and lymphatic vessels, in which the junctions between endothelial cells are very tight or very open. The ERC grant, amounting to EUR 2.5 million over 5 years, will allow us to conduct conceptually ambitious research, with a high-tech approach. It gives us an even more competitive advantage and a capacity for discoveries with translational and therapeutic potential.