Most eukaryotic cells secrete numerous membrane-derived vesicles of 30-150 nm in size termed exosomes. As an emerging mechanism for cell-to-cell communication, exosomes have been recently found to play important roles in a wide range of biological processes, including cancer development and metastasis. For instance, increasing evidences support the cancer-derived exosomes can reprogram the behavior of recipient cells to promote tumor growth and metastasis. Despite the significance of exosomes, our understanding of their biogenesis, molecular classification, and biological functions remain very limited. One of the challenges is to analyze exosomes released from single cells. Because cells in a tumor are known to be remarkably heterogeneous, single-cell analysis of exosomes is crucial to understanding their pathological roles in cancer. However, current ?gold standard? methods can only perform ensemble measurements of exosomes released from a large cell population because of their poor isolation yield, insufficient analysis sensitivity and low throughput. In this proposal, the PI aims to develop for the first time a high-throughput single cell exosome analysis system (SCEAS) capable of probing the secretion and molecular composition of exosomes at the single cell level. The goal will be achieved via two specific aims: 1) Develop a microfluidic digital barcode system for multiplexed, ultrasensitive exosome profiling; and 2) Establish a Single Cell Exosome Analysis System (SCEAS) for quantitative profiling of exosomes derived from single cancer cells. Success of the work will yield a key tool to enable the studies of heterogeneous exosome release by tumor cells at the single cell level, which would facilitate better understanding of intercellular signaling pathways underlying cancer development, metastasis, and drug resistance.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
5P20GM103638-08
Application #
9754182
Study Section
Special Emphasis Panel (ZGM1)
Project Start
Project End
Budget Start
2019-07-01
Budget End
2020-06-30
Support Year
8
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Kansas Lawrence
Department
Type
DUNS #
076248616
City
Lawrence
State
KS
Country
United States
Zip Code
66045
Zhu, Qingfu; Heon, Mikala; Zhao, Zheng et al. (2018) Microfluidic engineering of exosomes: editing cellular messages for precision therapeutics. Lab Chip 18:1690-1703
Pacelli, Settimio; Basu, Sayantani; Berkland, Cory et al. (2018) Design of a cytocompatible hydrogel coating to modulate properties of ceramic-based scaffolds for bone repair. Cell Mol Bioeng 11:211-217
Wessinger, Carolyn A; Kelly, John K; Jiang, Peng et al. (2018) SNP-skimming: A fast approach to map loci generating quantitative variation in natural populations. Mol Ecol Resour 18:1402-1414
Zhang, Peng; Crow, Jennifer; Lella, Divya et al. (2018) Ultrasensitive quantification of tumor mRNAs in extracellular vesicles with an integrated microfluidic digital analysis chip. Lab Chip 18:3790-3801
Klaus, Jennifer R; Deay, Jacqueline; Neuenswander, Benjamin et al. (2018) Malleilactone Is a Burkholderia pseudomallei Virulence Factor Regulated by Antibiotics and Quorum Sensing. J Bacteriol 200:
Abisado, Rhea G; Benomar, Saida; Klaus, Jennifer R et al. (2018) Bacterial Quorum Sensing and Microbial Community Interactions. MBio 9:
Hill, Tom; Unckless, Robert L (2018) The dynamic evolution of Drosophila innubila Nudivirus. Infect Genet Evol 57:151-157
Bandyopadhyay, Arnab; Wang, Huijing; Ray, J Christian J (2018) Lineage space and the propensity of bacterial cells to undergo growth transitions. PLoS Comput Biol 14:e1006380
Kaplan, Sam V; Limbocker, Ryan A; Levant, Beth et al. (2018) Regional differences in dopamine release in the R6/2 mouse caudate putamen. Electroanalysis 30:1066-1072
Reiner, David J; Lundquist, Erik A (2018) Small GTPases. WormBook 2018:1-65

Showing the most recent 10 out of 134 publications