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.
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.
Ricklefs, Franz L; Alayo, Quazim; Krenzlin, Harald et al. (2018) Immune evasion mediated by PD-L1 on glioblastoma-derived extracellular vesicles. Sci Adv 4:eaar2766 |
Zhou, Shuang; Appleman, Vicky A; Rose, Christopher M et al. (2018) Chronic platelet-derived growth factor receptor signaling exerts control over initiation of protein translation in glioma. Life Sci Alliance 1:e201800029 |
Reátegui, Eduardo; van der Vos, Kristan E; Lai, Charles P et al. (2018) Engineered nanointerfaces for microfluidic isolation and molecular profiling of tumor-specific extracellular vesicles. Nat Commun 9:175 |
Boussiotis, Vassiliki A; Charest, Alain (2018) Immunotherapies for malignant glioma. Oncogene 37:1121-1141 |
Marangoni, Francesco; Zhang, Ruan; Mani, Vinidhra et al. (2018) Tumor Tolerance-Promoting Function of Regulatory T Cells Is Optimized by CD28, but Strictly Dependent on Calcineurin. J Immunol 200:3647-3661 |
Gustafsson, Gabriel; Lööv, Camilla; Persson, Emma et al. (2018) Secretion and Uptake of ?-Synuclein Via Extracellular Vesicles in Cultured Cells. Cell Mol Neurobiol 38:1539-1550 |
György, Bence; Lööv, Camilla; Zaborowski, Miko?aj P et al. (2018) CRISPR/Cas9 Mediated Disruption of the Swedish APP Allele as a Therapeutic Approach for Early-Onset Alzheimer's Disease. Mol Ther Nucleic Acids 11:429-440 |
Shao, Huilin; Im, Hyungsoon; Castro, Cesar M et al. (2018) New Technologies for Analysis of Extracellular Vesicles. Chem Rev 118:1917-1950 |
Maas, Sybren L N; Breakefield, Xandra O; Weaver, Alissa M (2017) Extracellular Vesicles: Unique Intercellular Delivery Vehicles. Trends Cell Biol 27:172-188 |
Wu, Anthony Yan-Tang; Lai, Charles Pin-Kuang (2017) Tracking Extracellular Vesicles Delivery and RNA Translation Using Multiplexed Reporters. Methods Mol Biol 1660:255-265 |
Showing the most recent 10 out of 37 publications