hart_vol

Franck Lebrin, PhD

Franck Lebrin did a PhD in cell biology in the CEA Grenoble. After a post-doc in The Netherlands Cancer Institute (NKI) in Amsterdam with Peter ten Dijke and a post-doc in the Hubrecht Laboratorium in Utrecht with Christine Mummery, he became INSERM researcher and set up his group at the Collège de France in Paris. He recently came to LUMC.
Overview. In my lab, we are interested in signaling between endothelial cells and pericytes with particular emphasis on how alterations in communication between these two cell types affect blood vessel functions and contribute to the progression of vascular related diseases such as Hereditary Hemorrhagic Telangiectia (HHT), neurodegeneration and cancer.
Pericytes are obligatory components of the blood capillaries that regulate angiogenesis by promoting vessel stabilization. They modulate local blood flow and control permeability to molecules and immune cells. Many pericyte functions are disrupted in disorders like diabetic retinopathy, neurodegeneration, stroke or cancers. However, despite their important role in health and diseases, little is known about the biology of these cells and the relevant signaling pathways. How are pericyte functions altered in disease and can they be manipulated to improve therapies?
Recently, we obtained proof-of-principle that by targeting pericytes, we induce vessel stabilization, so that blood vessel leakiness caused by HHT or by brain irradiation is reduced. Thalidomide was particularly effective in this in both mice and patients suggesting that it may be useful in other disorders with similar underlying pathology. However, Thalidomide lacks target specificity and cause side effects. It can only be prescribed in severely affected patients. Here, we intend to develop new drugs that specifically target pericytes with the ultimate goal of using them in clinical trials in patients with HHT, undergoing radiation therapy and receiving cancer treatment.
We aim to:
1-Characterize the different pericyte sub-populations.
2-Determine the contribution of these pericyte sub-populations to regulating angiogenesis, local blood flow and vessel permeability.
3-Determine the mechanisms underlying vessel instability in HHT.
4-Determine the mechanisms that lead to blood brain barrier disruption following irradiation.
5-Validate therapeutic approaches inducing vessel stabilization to treat vascular diseases and cancer.
We use a combination of cellular, molecular, genetic and imaging approaches to understand pericyte biology and develop tools and models for drug testing. These include pluripotent embryonic stem cell models, single cell electrophysiology, transgenic mouse lines, 2-photon and ultrafast ultrasound imaging technologies.