Richard Daneman earned his bachelor's degree in biochemistry from McGill University in Montreal, Canada, and his PhD in developmental biology from Stanford University. From 2009 to 2014 he was a Sandler Fellow with the Department of Anatomy at UC San Francisco.
The goal of his research is to understand the cellular and molecular mechanisms that regulate the blood-brain barrier (BBB) 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 central nervous system (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.
Dr. Daneman's lab uses a combination of cellular, molecular and genetic approaches to understand the mechanisms of BBB formation and function. They are addressing the following questions:
- What are the molecules in CNS vascular cells that form the BBB?
- What are the signaling mechanisms that regulate the formation of the BBB during development, and dynamic function throughout life?
- What are the molecular mechanisms that lead to BBB disruption during neurological disease?
His goal is to elucidate these mechanisms so therapeutics can be developed to rebuild the barrier to treat neurological diseases, as well as methods to bypass the barrier to deliver drugs to the CNS.
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
J Neuroscience In Press.
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.
Steketee MB, Moerdyk C, Daneman R, Trakhtenberg E, Lamoureaux P, Weisten J, Heidemann S, Barres BA, Goldberg JL
Regulation of intrinsic axon growth ability at retinal ganglion cell growth cones
IOVS, 2014 Jun 6. pii: IOVS-14-13882
Purification and Culture of central nervous system pericytes
Zhou L, Sohet F, Daneman R.
Cold Spring Harb Protoc. 2014 Jun 2;2014(6)
Zhou L, Sohet F. Daneman R
Purification and culture of central nervous system endothelial cells
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.
Siegenthaler JA, Choe C, Patterson KP, Hsieh I, Li D, Jaminet S, Daneman R, Kume T, Huang EJ, Pleasure SJ.
Foxc1 is required by pericytes during fetal brain angiogenesis
Biol Open. 2013 May 20;2(7):647-59
Sohet F, Daneman R
Genetic mouse models to study blood-brain barrier development and function
Fluids and Barriers of the CNS, 2013 Jan 10;10(1):3
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.
Dugas JC, Mandemakers W, Rogers M, Ibrahim A, Daneman R, Barres, BA.
A novel purification method for CNS projection neurons leads to the identification of brain vascular cells as a source of trophic support for corticospinal motor neurons.
J Neuroscience. 2008 Aug 13;28(33):8294-305.
Daneman R, Barres BA.
The blood-brain barrier--lessons from moody flies.
Cell. 2005 Oct 7;123(1):9-12.
Morin X, Daneman R, Zavortink M, Chia W.
A protein trap strategy to detect GFP-tagged proteins expressed from their endogenous loci in Drosophila.
Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15050-5.
Jankowski A, Kim JH, Collins RF, Daneman R, Walton P, Grinstein S.
In situ measurements of the pH of mammalian peroxisomes using the fluorescent protein pHluorin.
J Biol Chem. 2001 Dec 28;276(52):48748-53.
Kim JH, Johannes L, Goud B, Antony C, Lingwood CA, Daneman R, Grinstein S.
Noninvasive measurement of the pH of the endoplasmic reticulum at rest and during calcium release.
Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):2997-3002.
Theis JG, Koren G, Daneman R, Sherwin AL, Menzano E, Cortez M, Hwang P.
Interactions of clobazam with conventional antiepileptics in children.
J Child Neurol. 1997 Apr;12(3):208-13.