Willnow group – Metabolic basis of neurodegeneration

The Willnow group studies the interconnection between systemic metabolism and the brain. Specifically, they wish to understand how energy homeostasis controls functional integrity of the brain and why metabolic disturbances are a major cause of neurodegenerative disease. In their work, they combine human genetics with functional studies in humanized mouse and iPSC-derived cell models to address fundamental principles in brain (patho)physiology and to establish novel therapeutic concepts to combat age-related dementia.

Research focus

Alzheimer’s disease (AD) is the most common form of age-related dementia affecting millions of patients. Disturbingly, disorders of the metabolism, such as obesity, diabetes, and dyslipidemia emerge as major risk factors for AD, causally linking two disease entities of epidemic proportions.

In their work, the Willnow group aims at elucidating the molecular mechanisms whereby metabolites control functional integrity of the brain, and why alterations in systemic energy homeostasis are a major cause of AD. Capitalizing on recent technological developments, they study brain metabolism at a global scale using -omics technologies and re-enact human disease processes in humanized mouse and iPSC-derived cell and organoid models.

Recently, their work has focused on functional elucidation of a specialized group of intracellular sorting receptors, called VPS10P domain receptors that act as dual regulators of systemic metabolism and neuronal viability. In these studies, they uncovered the significance of these receptors for control of systemic and brain lipid metabolism and why receptor dysfunctions are a cause of sporadic but also familial forms of AD. In ongoing work, they now elucidate the molecular mechanisms of VPS10P domain receptor action in brain lipid homeostasis and explore receptor pathways as therapeutic target in treatment of neurodegeneration.

Projects for Master, PhD students and postdoctoral researchers currently available

If interested, please contact Ass. Professor (fabia.febbraro@biomed.au.dk) for further information.