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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-OBT-S (50))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Massachusetts General Hospital
United States
Zip Code
Maas, Sybren L N; Breakefield, Xandra O; Weaver, Alissa M (2017) Extracellular Vesicles: Unique Intercellular Delivery Vehicles. Trends Cell Biol 27:172-188
Yeo, Alan T; Charest, Alain (2017) Immune Checkpoint Blockade Biology in Mouse Models of Glioblastoma. J Cell Biochem 118:2516-2527
Wei, Zhiyun; Batagov, Arsen O; Schinelli, Sergio et al. (2017) Coding and noncoding landscape of extracellular RNA released by human glioma stem cells. Nat Commun 8:1145
Pucci, Ferdinando; Garris, Christopher; Lai, Charles P et al. (2016) SCS macrophages suppress melanoma by restricting tumor-derived vesicle-B cell interactions. Science 352:242-6
van der Vos, Kristan E; Abels, Erik R; Zhang, Xuan et al. (2016) Directly visualized glioblastoma-derived extracellular vesicles transfer RNA to microglia/macrophages in the brain. Neuro Oncol 18:58-69
Wei, Zhiyun; Batagov, Arsen O; Carter, David R F et al. (2016) Fetal Bovine Serum RNA Interferes with the Cell Culture derived Extracellular RNA. Sci Rep 6:31175
Zappulli, Valentina; Friis, Kristina Pagh; Fitzpatrick, Zachary et al. (2016) Extracellular vesicles and intercellular communication within the nervous system. J Clin Invest 126:1198-207
Soares, Vitor Y R; Atai, Nadia A; Fujita, Takeshi et al. (2016) Extracellular vesicles derived from human vestibular schwannomas associated with poor hearing damage cochlear cells. Neuro Oncol 18:1498-1507
Hall, Justin; Prabhakar, Shilpa; Balaj, Leonora et al. (2016) Delivery of Therapeutic Proteins via Extracellular Vesicles: Review and Potential Treatments for Parkinson's Disease, Glioma, and Schwannoma. Cell Mol Neurobiol 36:417-27
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

Showing the most recent 10 out of 28 publications