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Photo of Lutz, Sarah E

Sarah E Lutz, PhD

Assistant Professor

Mentor, Biological Mechanisms

Department of Anatomy and Cell Biology


Building & Room:

COMRB 7093

Office Phone:



Building & Room:

COMRB 7088

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Dr. Lutz’s research is directed to an understanding of the role of the Blood Brain Barrier (BBB) in neuroinflammatory diseases. She has a particular focus on vascular remodeling and immune cell infiltration of target organs in animal models for Multiple Sclerosis, but also is interested in cellular migration across biologic barriers in regenerative medicine, cancer metastasis and inflammatory bowel disease. She uses both genetic and pharmacological approaches to modify BBB permeability and intravital and ex vivo imaging technologies. Signal transduction pathways of interest include Wnt/beta-catenin and Caveolin-1.


Blood brain barrier disruption and repair in mouse models of human disease
In CNS disorders including multiple sclerosis, stroke, cancer, and others, disruption of the blood-brain barrier (BBB) leads to tissue damage and deleterious clinical outcome by enabling infiltration of leukocytes and serum proteins. Barrier function is normally maintained by integrity of tight junctions (restricting paracellular permeability), suppression of caveolar transcytosis (transcellular permeability), and specific ion transporters. We have taken genetic, functional, and in vivo imaging approaches to uncover new aspects of barrier regulation, which have profound implications for disease and recovery, in the middle cerebral artery occlusion (MCAO) model of stroke and the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis. Using in vivo two photon imaging in transgenic eGFP-Claudin5 mice with fluorescent tight junctions, we have identified dynamic BBB remodeling events that would be impossible to appreciate in fixed tissue preparations. We demonstrate regional anatomic differences in endothelial cell tight junction recycling, which may partially explain the enigmatic preferential vulnerability of the spinal cord to EAE. In MCAO, BBB breakdown occurs in two waves: first transcellular, then paracellular permeability. In EAE, this sequence is reversed. We find that remodeling of TJs precedes the onset of EAE clinical signs in mice and coincides with paracellular BBB leakage. In contrast, transcellular BBB leakage to albumin occurs later, at the peak of disease. Moreover, mice that lack caveolae have reduced EAE clinical severity. These findings suggest that TJ dissolution initiates disease onset, whereas caveolar transcytosis may enhance EAE severity. These findings also have relevance for BBB disruption in multiple neuroinflammatory states.

To establish novel methods to restore BBB integrity, we investigated the Wnt/β-catenin pathway, which is critical for BBB development. There exists an urgent need for new molecular strategies to protect and restore BBB function, either by strengthening tight junctions or suppressing trans-endothelial vesicular transcytosis. We have shown Wnt/β-catenin pathway upregulation in BBB endothelial cells in active lesions in MS brains and in the animal model experimental autoimmune encephalomyelitis (EAE) using detection of transcriptional targets Sox17 and Apcdd1 and the TCF/LEF1::H2B::eGFP β-catenin reporter mouse. We observed ligand dependent activation by neuronal expression of Wnt3 and ligand independent activation by liberation of β-catenin from adherens junctions. Genetic β-catenin loss of function in endothelial cells exacerbated EAE clinical presentation, demyelination, and CNS T cell infiltration. β-catenin loss of function enhanced endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) and the transcytosis protein Caveolin-1, without disrupting tight junction proteins. These results suggest that re-activation of the developmental Wnt/β-catenin pathway in CNS endothelial cells is an endogenous BBB repair mechanism.