Richard Daneman, Ph.D.
Associate Professor of Pharmacology and Neurosciences
Richard Daneman, Ph.D.
Associate Professor of Pharmacology and Neurosciences
Research Interests
Our goal is to understand the cellular and 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. 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. We use a combination of cellular, molecular and genetic approaches to understand the mechanisms of BBB formation and function. We are interested in asking:
- How is the BBB formed during development?
- How does the BBB interact with neuronal circuitry to regulate brain function and behavior?
- 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.
Selected Publications
Dorrier CE, Aran D, Haenelt EA, Sheehy RN, Hoi KK, Pintaric L, Chen Y, Lizama CO, Cautivo KM, Weiner GA, Popko B, Fancy SPJ, Arnold TA, Daneman R. CNS fibroblasts form a fibrotic scar in response to neuroinflammation. Nature Neuroscience. 2021 Feb;24(2):234-244.
Pulido RS, Munji RN, Chan TC, Quirk CR, Weiner GA, Weger BD, Rossi MJ, Elmsaouri S, Malfavon M, Deng A, Profaci CP, Blanchette M, Qian T, Foreman KL, Shusta EV, Gorman MR, Gachon F, Leutgeb S, Daneman R. Neural Activity Regulates Blood-Brain Barrier Efflux Transport through Endothelial Circadian Genes. Neuron. 2020 Dec 9;108(5):937-952
Munji RN*, Soung AL*, Weiner GA, Sohet F, Semple BD, Trivedi A, Gimlin K, Kotoda M, Korai M, Aydin S, Batugal A, Cabangcala AC, Schupp PG, Oldham MC, Hashimoto T, Noble-Haeusslein LJ, Daneman R. Profiling the mouse brain endothelial transcriptome in health and disease models reveals a core blood-brain barrier dysfunction module. Nature Neuroscience. 2019 Nov;22(11):1892-1902.
Tsai HH, Niu J, Munji R, Davalos D, Chang J, Zhang H, Tien AC, Kuo CJ, Chan JR, Daneman R, Fancy SP. Oligodendrocyte precursors migratenalong vasculature in the developing nervous system. Science. 2016 Jan 22;351(6271):379-84. doi: 10.1126/science.aad3839.
Sohet F, Lin C, Munji RN, Lee SY, Ruderisch N, Derugin N, Vexler ZS, Yen FT, Daneman R. LSR/Angulin-1, a tricellular tight junction protein involved in blood-brain barrier formation. Journal of Cell Biology. 2015 Mar 16;208(6):703-11
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.