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)
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Special Emphasis Panel (ZRG1-OBT-S)
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Massachusetts General Hospital
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Redzic, Jasmina S; Balaj, Leonora; van der Vos, Kristan E et al. (2014) Extracellular RNA mediates and marks cancer progression. Semin Cancer Biol 28:14-23
Bauer, Christian A; Kim, Edward Y; Marangoni, Francesco et al. (2014) Dynamic Treg interactions with intratumoral APCs promote local CTL dysfunction. J Clin Invest 124:2425-40
Nery, Flavia C; da Hora, Cintia C; Atai, Nadia A et al. (2014) Microfluidic platform to evaluate migration of cells from patients with DYT1 dystonia. J Neurosci Methods 232:181-8
Maguire, Casey A; Ramirez, Servio H; Merkel, Steven F et al. (2014) Gene therapy for the nervous system: challenges and new strategies. Neurotherapeutics 11:817-39
Vader, Pieter; Breakefield, Xandra O; Wood, Matthew J A (2014) Extracellular vesicles: emerging targets for cancer therapy. Trends Mol Med 20:385-93
Rajendran, Lawrence; Bali, Jitin; Barr, Maureen M et al. (2014) Emerging roles of extracellular vesicles in the nervous system. J Neurosci 34:15482-9
Lai, Charles P; Mardini, Osama; Ericsson, Maria et al. (2014) Dynamic biodistribution of extracellular vesicles in vivo using a multimodal imaging reporter. ACS Nano 8:483-94