Project Leader: Stephen Gould The biogenesis and intercellular transfer of functional, extracellular RNA (exRNA) is being detected in an ever-increasing array of biological systems. Intercellular traffic of exRNA plays important roles in human health and disease, and exRNA-mediated systems for disease detection, monitoring, and therapy have a high yet currently untapped potential. However, the molecular mechanisms that cells use to generate exRNAs are only poorly understood, and there is virtually nothing known about the mechanisms of exRNA uptake by human cells. This proposal will advance our mechanistic understanding of exRNA biogenesis and uptake using a glioblastoma multiforme (GBM) model system that focuses on the production of exRNAs by GBM cells, and their uptake by surrounding somatic cell types such as astrocytes, microglia, and brain endothelial cells. The successful completion of this proposal will shed light on the mechanisms of intercellular RNA trafficking, test the scope and limitations of these mechanisms, and generate technologies for the engineered production and uptake of exRNA in human and rodent cell systems.

Public Health Relevance

This proposal will advance our understanding of how genetic information can be transferred from one cell to another. It will also explore the relevance of this process to cancer biology, and brain tumors in particular.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program--Cooperative Agreements (U19)
Project #
1U19CA179563-01
Application #
8590455
Study Section
Special Emphasis Panel (ZRG1-OBT-S (50))
Project Start
2013-09-01
Project End
2018-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
1
Fiscal Year
2013
Total Cost
$414,536
Indirect Cost
$83,304
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
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Abels, Erik R; Breakefield, Xandra O (2016) Introduction to Extracellular Vesicles: Biogenesis, RNA Cargo Selection, Content, Release, and Uptake. Cell Mol Neurobiol 36:301-12

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