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Ingrid Molema, September 25

SciLifeLab The Svedberg seminar series Thursday, September 25

Ingrid Molema

Dept. Pathology and Medical Biology, Medical Biology section , University of Groningen,Groningen, The Netherlands

Ingrid Molema, Ph.D., heads the laboratory for Endothelial Biomedicine and Vascular Drug Targeting research at the University Medical Center Groningen (UMCG), the Netherlands. The aim of the research of her team is to molecularly unravel microvascular endothelial cell dysfunction in inflammatory diseases and cancer, and translate the findings to better (targeted) therapeutic interventions for clinical application. Dr. Molema (49) is professor of Life Sciences since 2004 and actively participates in Life Sciences bachelor and master courses, in the program of the Graduate School of Medical Sciences of UMCG, as well as in high school and primary school science programs.

Microvascular endothelial specific drug delivery – from a therapeutic strategy to a tool for in vivo endothelial biology studies.

The microvasculature in the body is highly heterogeneous with regard to function. The tight blood brain barrier protects the brain against harmful molecules and events, while the glomerular filtration barrier in the kidney functions as a semipermeable sieve to filter the blood, and the sinusoidal capillaries in the liver allow full access of blood constituents to hepatic clearance systems.

The endothelial cells in these microvascular capillaries are highly heterogenic with respect to their gene and protein expression profiles, both under quiescent, healthy conditions, and in response to disease initiation and development. Though molecularly not very well understood, this heterogeneity provides a unique opportunity to develop microvascular endothelial cell specific drug delivery systems to therapeutically interfere with specific microvascular segments in the body.

The lecture will address the issue of microvascular heterogeneity and the application thereof to the design of drug delivery systems. Examples of the delivery of anti-inflammatory drugs to specific microvascular endothelial subsets in mouse models of disease will be given, and cell biological and pharmaceutical issue will be discussed in the light of ongoing improvement of the design of these systems.

Endothelial cells show extensive gene drift when being taken from an organ and put into culture, which makes translation of in vitro data to the in vivo context a difficult task. Microvascular endothelial specific drug delivery systems are expected to become essential tools for creating a better understanding of endothelial cell biology in the complexity of the tissue, as local gene knock outs can be created in vivo by targeted delivery of siRNA. In the lecture some proof-of-concept studies and validation of effects by novel read out systems developed in our laboratory will be shown.

Host: Anna-Karin Olsson