Speaker

Richard Daneman, University of California San Diego, USA

Richard Daneman

Richard Daneman received his Bachelor of Science McGill University, in Montreal Canada majoring in biochemistry. Daneman then received his Ph.D in developmental biology from Stanford University where he studied the molecular mechanisms that regulate blood-brain barrier (BBB) formation in the laboratory of Dr. Ben Barres. Daneman then started his own lab as a Sandler Fellow at University of California, San Francisco, before moving to a position as Assistant Professor in the departments of Pharmacology and Neuroscience at the University of California, San Diego. Daneman focuses his studies on understanding the molecular mechanisms that regulate BBB function during health and disease. In his lab, he uses a combination of cellular, molecular and genetic approaches to understand the mechanisms of BBB formation and function, addressing important questions such as: 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? The overall goal of his 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.



Presentation abstract

Regulation of the blood-brain barrier in health and disease
Richard Daneman, PhD
Departments of Pharmacology and Neurosciences,
University of California, San Diego
9500 Gilman Dr. BSB 3092
La Jolla, CA, USA 92093
Email: rdaneman@ucsd.edu
Email addresses are provided for information in connection with the authors presentation only. Please do not mail credit card information under any circumstances.

Vascular endothelial cells in the CNS form a barrier that restricts the movement of molecules and ions between the blood and the brain. This blood-brain barrier is crucial to ensure proper neuronal function and to protect the CNS from injury and disease.  Although the properties of the barrier are manifested in the endothelial cells, transplantation studies have demonstrated that the properties of the blood-brain barrier is not intrinsic to the endothelial cells, but is induced by interactions with the neural cells.

We have used genomic, genetic, and molecular approaches to elucidate the cellular and molecular mechanisms that regulate the formation and function of the blood-brain barrier.  These approaches have allowed us to identify the crucial role of pericytes in regulating the permeability of CNS vessels by inhibiting the properties that make endothelial cells leaky. In particular, pericytes limit the rate of transcytosis through endothelial cells, as well as the expression of leukocyte adhesion molecules in CNS endothelial cells, which in turn limits CNS infiltration of immune cells. Furthermore, we have developed methods to purify and transcriptionally profile endothelial cells from different tissues and, by comparing the transcriptional profile of brain endothelial cells with those purified from the liver and lung, we have generated a comprehensive resource of transcripts that are specifically expressed in endothelial cells that form the brain-blood barrier.    We have further examined the profile of CNS endothelial cells following injury and disease, and have identified molecular mechanisms by which pericytes control BBB formation, which are then disrupted during neurological disease leading to BBB dysfunction. 

Funding
NIH/NINDS
Takeda Pharmaceuticals
Rita Allen Foundation
Klingenstein-Simons Fellowship
UCSF Program for Breakthrough Biomedical Research
National Multiple Sclerosis Society

Conflict of interests: Richard Daneman is a consultant for Alector but their products will not be discussed

 

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Supporting Publications
Organised by
 
  • Elsevier
  • TLP
  • TLN
Exhibitors
 
  • Autoimmune Encephalitis (AE) Alliance
  • Encephalitis Society
  • Treating Autism
Sponsors
 
  • Encephalitis Society
  • Epitech
  • Treating Autism