SciLifeLab The Svedberg seminar series, Christer Betsholtz
Monday October 26
Department of Medical Biochemistry and Biophysics, Div. Vascular Biology, Karolinska institutet and Department of Immunology, Genetics and Pathology, Uppsala University, Sweden
Christer Betsholtz took his PhD in 1986 at Uppsala University and has since then held positions at Göteborg University 1994-2004 and Karolinska Institutet 2004-today. Since 2013 he is professor of vascular and tumor biology at Uppsala university, Department of Immunology, Genetics and Pathology. His main research interests are in the area of vascular biology, where he explores the biology of endothelial cells and pericytes during microvessel formation and remodelling in health and disease.
Platelet-derived growth factors, pericytes, the blood-brain barrier, and disease: new insights and surprises.
One of the key roles for PDGF-B signaling via the PDGFR-beta receptor is to recruit pericytes to newly formed blood vessels. Certain mouse mutants with decreased PDGF-B/R-beta signaling have less pericytes but live into adulthood making them useful models for studies of the role of pericytes in physiology and disease. We found that such pericyte-deficient mice display an abnormally permeable blood-brain barrier, opened through the activation of a transcytosis mechanism that involves pinocytotic vesicles able to carry proteins such as antibodies. We are currently exploring the ability of this pathway to deliver meaningful concentrations of therapeutic antibodies to the brain for the treatment of neurodegenerative diseases. We are also studying PDGFB/R-beta mutant mice as models for the rare human genetic disease primary familial brain calcification (PFBC), which is characterized by brain region-specific microvascular calcification. Here, we focus on the mechanisms of vascular calcification hoping that the insights will uncover targets for pharmacological intervention as well as shedding light on other, more common, vascular calcification processes.
Host: Carl-Henrik Heldin