Undergraduate Fellowship Awarded

Congratulations Harry, a rising senior Biology major at UIC, for receiving a merit-based award from LASURI to support his research addressing the protein Caveolin-1 in neurovascular inflammation. Harry previously received the Chancellor’s Undergraduate Research Award.

New lab members

Congratulations to new lab member Andrea Ochoa-Raya for being awarded fellowships from LASURI and from the Latin@s Gaining Access to Networks for Advancement in Science (L@SGANAS) for undergraduate research at UIC in the Lutz lab. Welcome also to lab volunteer Elizabeth Pietruczyk and UIC undergrad Mary Horne.

Putting the squeeze on the blood-brain barrier

Our newest publication is out in Cell Reports. We showed that Th17 and Th1 lymphocytes use different mechanisms to cross the blood-brain barrier – and cause disease – in animal models of multiple sclerosis. Surprisingly, a majority of Th1 cells actually squeeze through the endothelial cell cytoplasm instead of going through gaps between cells. This process requires endothelial caveolae. Part of the agenda for the Lutz lab is building upon these findings for new ways to therapeutically block or enhance blood-brain barrier permeability. A second surprising finding was that caveolae are not involved in the internalization and destruction of large tight junction segments in the living blood-brain barrier.

This work was done during my post-doctoral training in the lab of Dr. Dritan Agalliu at Columbia University Medical Center, with significant guidance on intravital two-photon microscopy from Dr. Sunil Gandhi at University of California, Irvine.  Thanks to excellent collaborators Julian Smith, Dae Hwan (Glenn) Kim, Carl Olson, Kyle Ellefsen, and Jennifer Bates.

Full text can be viewed at the Cell Reports website: http://www.cell.com/cell-reports/fulltext/S2211-1247(17)31574-7

Study published in Proceedings of the National Academy of Sciences

My co-first-author paper describing a novel role for the Wnt/beta-catenin signaling pathway in protection of blood-brain barrier endothelial cells has been published in Proceedings of the National Academy of Sciences on January 30, 2017 (Lengfeld, Lutz, et. al.). Endothelial cells (ECs) in the CNS form a unique blood–brain barrier (BBB) that is broken down in multiple sclerosis (MS). New therapies are sorely needed to restore BBB function in this disease. The wingless integrated MMTV (Wnt)/β-catenin pathway, which is essential for barrier formation, is activated in CNS ECs in MS and the animal model experimental autoimmune encephalomyelitis. When this pathway is inhibited in ECs before disease onset, mice develop more severe disease, with more immune cells entering the CNS owing to increased levels of proteins that promote interactions of immune cells with blood vessels and caveolar transport across vessels. Our findings suggest that pharmacologic enhancement of Wnt signaling may be helpful to limit BBB damage and CNS immune cell infiltration in MS. This work was conducted at the University of California Irvine and at Columbia University Medical Center.

Figure 1. Endothelial cell Wnt/b-catenin activation protects the neurovascular unit in the EAE model of multiple sclerosis. A) In the absence of Wnt signaling, neuroinflammation is exacerbated by elevated caveolar transcytosis and vascular cell adhesion molecule (VCAM-1) expression. B) Wnt/β-catenin mediated transcription suppresses caveolar transcytosis and VCAM-1 expression, markedly reducing T cell infiltration into the CNS.

View the abstract at: http://www.pnas.org/content/early/2017/01/26/1609905114.abstract

About Dr. Lutz

I am the principal investigator of a translational research lab at University of Illinois at Chicago. My research interest is in how junctional molecules of the central nervous system (CNS) influence neuroinflammatory diseases such as multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE).

I am studying the processes by which blood-borne solutes and cells traverse the CNS endothelium using novel transgenic mice expressing fluorescently labeled BBB proteins in brain and spinal cord endothelial cells. I am particularly interested in whether canonical Wnt ligands, which are important in BBB development, also regulate BBB function in the adult. Imaging is conducted in cultured endothelial cells and in EAE mice using time lapse imaging and two-photon microscopy. The goal of these studies is to better elucidate mechanisms of blood brain barrier modulation in disease and recovery.

I obtained my PhD in 2010 from the Albert Einstein College of Medicine, where I studied gap junction molecules in astrocytes with Drs. Celia Brosnan and Cedric Raine. I conducted a postdoctoral fellowship with Dr. Eliana Scemes, where I showed that inhibiting one class of gap junctions blocked inflammasome formation and attenuated neuroinfolammatory disease. I completed a second fellowship with Dr. Dritan Agalliu at Columbia University College of Medicine in New York and at University of California, Irvine addressing molecular regulation of the blood-brain barrier.