Donatienne Tyteca

Major achievements

• Demonstration that lipids are not homogeneously distributed at the cell surface but form submicrometric domains that contribute to cell deformation
• Demonstration that the membrane cholesterol content is increased at the surface of breast cancer cells and contributes to cancer cell invasion
• Demonstration that specific lipid domains are lost from the red blood cell surface upon storage in red blood cell concentrates before transfusion

Question

What role do membrane lipids play in cellular deformation, how do lipids interact with cytoskeletal and membrane proteins and how is this interplay deregulated in diseases including cancer?

Research focus

Cell deformation is critical for numerous pathophysiological processes. Typical examples are the squeezing of red blood cells (RBCs) in the narrow pores of spleen sinusoïds, stretching of muscle cells during contraction or tumor cell invasion. We explore how plasma membrane lipid distribution and biophysical properties contribute to cell deformation and their deregulation in diseases.

Thus, using high-resolution confocal imaging and atomic force microscopy, we discovered the existence of several types of stable submicrometric lipid domains at the living human RBC surface. Those domains have differential lipid enrichment, biophysical properties and roles in the RBC deformation process. Lipid domains also contribute to myoblast migration. In contrast, some domains are lost from the RBC membrane by vesiculation during storage in RBC concentrates intended for blood transfusion. Furthermore, they deregulated in several RBC-related diseases and in breast cancer. Thus, plasma membrane lipids are more than structural components, contributing to cell deformation in different physiological contexts and being deregulated in a ex vivo physiological condition and pathology.

The group currently aims to unravel the interplay between plasma membrane lipids and cytoskeletal and membrane proteins during cell deformation. We also evaluate how lipid domains are lost by vesiculation during storage in concentrates, to provide strategies to limit vesiculation and thereby improve RBC functionality while limiting post-transfusion side effects. Another research line focuses on breast cancer and glioblastoma. We seek to develop new strategies to classify cancer subtypes or to help in the treatment of cancer.

Donatienne Tyteca obtained her Master’s degree in Pharmacy from the UCLouvain (Belgium) in 1996. She then joined the lab of Drs. Marie-Paule Mingeot-Leclercq and Paul Tulkens (Belgium), where she obtained her PhD in Pharmaceutical Sciences in 2001. She then moved to the Rijksuniversiteit Groningen (RUG) at Groningen (The Netherlands) in the group of Dr. Dick Hoekstra. She then joined the de Duve Institute in the group of Dr. Pierre Courtoy, first as Post-doctoral Researcher and then as a Group Leader and became an F.R.S-FNRS Research Associate and UCLouvain Associate Professor in 2013. She also leads the PICT imaging platform. In 2023, she was appointed F.R.S-FNRS Senior Research Associate.

Affiliations

• Group Leader, de Duve Institute
• Research Associate F.R.S.-FNRS
• PICT imaging platform Leader, de Duve Institute & UCLouvain Health Sector
• Assistant professor, UCLouvain