Our goal is to understand the molecular mechanisms that regulate blood-brain barrier (BBB) function during health and disease.
The BBB is a specialized structure formed by the blood vessels in the central nervous system (CNS) that is critical for proper brain function as well as protecting the brain from injury and disease. In most tissues the blood vessels are leaky allowing a relatively free flow of molecules and ions from blood into tissues, whereas in the brain, the blood vessels tightly restrict the movement of molecules and ions between the blood and the brain. This barrier clamps the extracellular environment allowing for proper neuronal communication while also limiting toxins, pathogens and even the body’s own immune system from entering and damaging the CNS. Breakdown of the BBB occurs during stroke, edema, brain trauma, and multiple sclerosis and is a major component of the symptoms and progression of these diseases. Furthermore, the BBB not only impedes the movement of toxins and pathogens, but also inhibits the delivery of potential therapeutic agents to the CNS.
We use a combination of cellular, molecular and genetic approaches to understand the mechanisms of BBB formation and function. We are interested in asking:
1. What are the molecules in CNS vascular cells that form the BBB?
2. What are the signaling mechanisms that regulate the formation of the BBB during development, and dynamic function throughout life?
3. How does the BBB interact with neuronal circuitry to regulate brain function and behavior?
4. What are the molecular mechanisms that lead to BBB disruption during neurological disease ?
The goal of our work is to elucidate these mechanisms, such that we will be able to develop therapeutics to rebuild the barrier to treat neurological diseases, as well as methods to bypass the barrier to deliver drugs to the CNS.
Rosen SD, Daneman R
High endothelial venules through a transcriptomic lens
Nature Immunology. 2014 Sep 18;15(10):906-8.
Zhang Y, Chen K, Sloan S, Bennett M, Scholze A, O’Keeffe S, Phatnani H, Guarnieri P, Caneda C, Ruderisch N, Deng S, Liddelow S, Zhang C, Daneman R, Maniatis T, Barres BA, Wu J
An RNA-Seq transcriptome and splicing database of neurons, glia, and vascular cells of the cerebral cortex
Journal of Neuroscience. 2014 Sep 3;34(36):11929-47
Yuen TJ, Silbereis JC, Daneman R, Fancy SPJ, Hengameh Z, Maltepe E, Rowitch DH.
Oligodendrocyte-encoded HIF function synchronizes postnatal myelination and white matter angiogenesis
Cell. 2014 Jul 17;158(2):383-96.
Zhou L, Sohet F, Daneman R.
Purification of pericytes from rodent optic nerve by immunopanning
Cold Spring Harb Protoc. 2014 Jun 2;2014(6)
Zhou L, Sohet F. Daneman R
Purification of endothelial cells from rodent brain by immunopanning
Cold Spring Harb Protoc. 2014 Jan 1;2014(1)
Obermeier B, Daneman R, Ransohoff RM.
Development, maintenance and disruption of the blood-brain barrier
Nature Medicine. 2013 Dec;19(12):1584-96.
Siegenthaler JA, Sohet F, Daneman R
‘Sealing off the CNS’: cellular and molecular regulation of blood-brain barriergenesis
Curr Opin Neurobiol. 2013 Dec;23(6):1057-64.
The blood-brain barrier in health and disease
Annals of Neurology, 2012 Nov;72(5):648-72
Fernández-López D, Faustino J, Daneman R, Zhou L, Lee SY, Derugin N, Wendland MF, Vexler ZS.
Blood-brain barrier permeability is increased after acute adult stroke but not neonatal stroke in the rat
J Neuroscience, 2012 Jul 11;32(28):9588-600
Foo LC, Allen NJ, Bushong EA, Chung WS, Zamanian JL, Zhou L, Cahoy JD, Daneman R, Ellisman MH, Barres BA.
Development of a Novel Method for the Purification and Culture of Mature Astrocytes.
Neuron. 2011 Sep 8;71(5):799-811
Crespo O, Kang SC, Daneman R, Lindstrom TM, Ho PP, Sobel RA, Steinman L, Robinson WH.
Tyrosine Kinase Inhibitors Ameliorate Autoimmune Encephalomyelitis in a Mouse Model of Multiple Sclerosis.
J Clin Immunol. 2011 Aug 17
Daneman R, Zhou L, Kebede AA, Barres BA.
Pericytes are required for blood-brain barrier integrity during embryogenesis.
Nature. 2010 Nov 25;468(7323):562-6.
Daneman R, Zhou L, Agalliu D, Cahoy JD, Kaushal A, Barres BA
The mouse blood-brain barrier transcriptome: a new resource for understanding the development and function of brain endothelial cells.
PLoS One. 2010 Oct 29;5(10):e13741.
Daneman R, Rescigno M.
The Gut Immune Barrier and the Blood-Brain Barrier: Are They So Different?
Immunity. 2009 Nov 20;31(5):722-35.
Daneman R, Agalliu D, Zhou L, Kuhnert F, Kuo CJ, Barres BA.
Wnt/beta-catenin signaling is required for CNS, but not non-CNS, angiogenesis.
Proc Natl Acad Sci U S A. 2009 Jan 13;106(2):641-6.