Research Activities
Overall goals
We aim at functional characterization of orphan endocytic receptors of the LDL receptor and Sortilin gene families, focusing on their roles in the cardiovascular and nervous system. Following a concept of molecular physiology we apply transgene technologies to generate model organisms with altered receptor expression (e.g., gene inactivation, transgene overexpression) and to study the consequences for organ function in vivo. Leads from animal experimentation are followed up by biochemical and cell biological studies to unravel the underlying molecular mechanisms of receptor activity. In recent years we have been mostly relying on the mouse as model system, but lately are also exploring alternatives such as the zebrafish.
In line with the mission of the MDC to carry out biomedical research into the causes of human diseases, our investigations of individual receptors center around three key questions:
What is the normal physiological function of the receptor?
Does the receptor contribute to disease processes?
If so, can the receptor be used as therapeutic drug target?
In the past five years, we concentrated on the characterization of two receptors, Megalin and SorLA. As outlined, we were able to identify Megalin as novel pathway for endocytic uptake of steroid hormones that plays essential roles in vitamin D metabolism as well as in development of brain and urogenital tract, and that represents a unique drug target to interfere with nephrotoxic side effects of therapeutic drugs. We uncovered SorLA as risk factor for Alzheimer disease.
