Katalin Völgyi obtained her doctoral thesis in molecular neurobiology in Budapest (Hungary) in 2016. After, she joined the Institute for Stroke and Dementia Research (ISD) (Munich, Germany) in 2017 as a postdoc. Her major research interest is in the research of early mechanism of small vessel disease (SVD), stroke and vascular cognitive impairment (VCI).
Cerebral SVD is a major cause of stroke and dementia for which there is currently only causal treatment. A recent genome-wide association study involving ISD investigators identified the FOXF2 gene region as a major risk locus for SVD, stroke and white matter hyperintensities. Foxf2 encodes a forkhead transcription factor expressed in brain pericytes and is required for pericyte differentiation, development and for maintenance of the blood-brain barrier (BBB). Foxf2 deficiency results in immature pericytes, BBB leakage, cerebral infarction, reactive gliosis and microhemorrhage, similar to the key manifestations of SVD in patients, but the exact mechanisms remain to be explored.
Katalin Völgyi studies the molecular, cellular and physiological mechanisms underlying SVD on Foxf2fl/fl mice. Her main aims are: i) to provide an in-depth characterization of vessel morphology (ultrastructure), white matter pathology, infarcts, hemorrhages, BBB integrity and behavior of adult Foxf2fl/fl;CAGGCreERT2 and Foxf2fl/fl;Pdgfrb-Cre mice thus establishing these strains as a new model for SVD, ii) to determine the effect of Foxf2 deficiency on the microvascular proteome for identification of key molecular targets and pathways in SVD, and iii) to explore the effect of Foxf2 deficiency on vascular physiology and the mechanisms linking pericyte dysfunction, BBB disruption and altered vascular physiology to neuronal loss.
To achieve these aims she employs cutting-edge technology including electron microscopy, LC-MS/MS applied to isolated microvessel preparations, and measurements of neurovascular coupling.
Aside from establishing Foxf2fl/fl as a novel mouse model for SVD this project will provide novel insights into the key mechanisms of SVD, both ischemic and hemorrhagic stroke, and white matter injury. In addition, the proposed experiments might establish the foundation for the development and rigorous testing of novel therapeutic strategies.