Stefan Constantinescu has been awarded the Tytgat prize

(News UCLouvain)

Prof. Stefan Constantinescu, researcher at the de Duve Institute of UCLouvain, has received the Alexandre and Gaston Tytgat Foundation Prize. This important prize is awarded every three years to French- and Flemish-speaking researchers in support of their cancer research.

On November 27, Stefan Constantinescu, professor at the Faculty of Medicine and Dentistry of UCLouvain and researcher at the de Duve Institute and at the Ludwig Institute for Cancer Research Brussels, received the 15th Alexandre and Gaston Tytgat Foundation Prize amounting to €25,000. This national prize is intended to support cancer research.

Hundreds of billions of blood cells

"Every day, explains Prof. Constantinescu on the Clap for Research website of the de Duve Institute, our body produces hundreds of billions of blood cells that carry oxygen to the tissues, protect us from infections and allow blood clotting in case of injury. All of these cells are formed from a blood stem cell ('hematopoietic') via a process called differentiation." Prof. Constantinescu's laboratory has identified acquired genetic mutations that cause the overproduction of some of these blood cells in a chronic way and can lead to a very serious blood cancer called 'secondary acute myeloid leukemia'.

Common cancers

"We have identified as targets of these genetic anomalies, continues the researcher, proteins expressed by stem cells that are intimately involved in the development of chronic blood cancers, called myeloproliferative neoplasms or MPNs. These cancers are common in the elderly (1 in 5,000 individuals)." NMPs are diseases that can cause abdominal and cerebral thrombosis (blood clot blocking blood vessels), or even myocardial infarction (although the primary cause is hematologic).

For the Tytgat Prize winner, it is essential to detect myeloproliferative neoplasms (MPNs) as early as possible in order to treat them effectively before their possible evolution into secondary acute myeloid leukemia.

Blocking these target proteins

"In our laboratory, we want to block these target proteins that are present on the surface of cells like antennae, and thus prevent the development of these chronic blood cancers." To do this, the researchers are analyzing the structure of these proteins at the atomic level (10-10 m) to develop a mechanism that will block their activities. The technique used consists of measuring the exchange between hydrogen atoms naturally present in the protein and deuterium atoms that can replace the hydrogen atoms but only in accessible areas of the protein. "This technique allows us to understand the functioning of these proteins in detail and to identify accessible, and therefore vulnerable, areas that could be targeted to reduce their activities. It also allows us to understand how mutant proteins interact with these 'antenna' proteins causing the overproduction of blood cells."

Towards a mapping

Nicolas Papadopoulos, a PhD student in the laboratory, has already succeeded in mapping the contact areas between one of the main mutant proteins causing NMPs and these 'antenna' proteins. This mapping can then be used to develop specific treatments to block this pathological interaction and thus prevent the development of NMPs. To establish and develop this high-tech approach for hematological targets, the laboratory is working with Didier Vertommen, who leads the mass spectrometry platform at the de Duve Institute.

Read more about the Tytgat Foundation (in French):

http://www.fondationtytgat.com/