The broad goal of this proposal is to develop and apply a novel sensing platform to detect and molecularly profile exosomes for monitoring tumor progression and treatment response in glioblastoma multiforme (GBM). Exosomes are membrane-bound phospholipid nanovesicles actively shed by cancer cells and the platform will be used to determine the abundance and composition of exosomes in serum. The candidate, Hyungsoon Im, has extensive experience in developing new sensing platforms with a background in engineering and now aims to transition to biomedical cancer research. Through the training, he will further develop skill sets to conduct independent translational research and make significant contribution to the field of cancer exosome research. This work will be conducted in the Center for Systems Biology at Massachusetts General Hospital and Harvard Medical School under the mentorship of Dr. Ralph Weissleder MD, PhD. To expand expertise, he has also brought in Xandra Breakefield, an internationally recognized expert in exosome biology and Prof. Antonio Chiocca, a neurosurgical oncologist with interest in translational work for additional mentoring and expertise. These members of the advisory committee will facilitate the transition of Hyungsoon's work toward a unique and independent line of investigation and allow him to develop a successful career as an independent biomedical cancer researcher. The research plan aims to first develop a microarray nano-plasmonic exosome sensing platform (nPLEX) for multiplexed profiling of exosome proteins and nucleic acids in serum. Exosomes have unique advantages as a circulating biomarker, but the quantification of their molecular composition has been challenging especially in clinical settings. This work stems from preliminary research using plasmonic nanoholes for sensitive detection of exosomes in a label-free manner and quantification of their marker expression levels.
In specific aim 1, an advanced nPLEX platform with 400 sensing arrays will be developed by integrating with state-of-the- art nanofabrication techniques and a high-throughput readout system.
In specific aim 2, the nPLEX platform will be applied for serial analyses of exosomes in GBM mouse models. Longitudinal assessment of exosomes pre- and post-treatment will be used to identify specific exosomes markers that correlate with tumor progression and treatment response to predict therapeutic efficacy. The proposed platform would allow comprehensive analyses of tumor-derived exosomes to shed light on molecular profiles of primary and metastatic tumors and provide information to guide efficient treatment schemes. The new nPLEX system could be a transformative tool facilitating cancer research and clinical practice.

Public Health Relevance

This project aims to develop a novel sensing platform to detect and molecularly profile exosome cancer biomarkers. The platform will allow gathering of comprehensive molecular information of tumors through high- throughput exosome profiling to monitor tumor progression and treatment response.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Transition Award (R00)
Project #
5R00CA201248-04
Application #
9547296
Study Section
Special Emphasis Panel (NSS)
Program Officer
Knowlton, John R
Project Start
2017-08-15
Project End
2020-07-31
Budget Start
2018-08-01
Budget End
2019-07-31
Support Year
4
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
Shao, Huilin; Im, Hyungsoon; Castro, Cesar M et al. (2018) New Technologies for Analysis of Extracellular Vesicles. Chem Rev 118:1917-1950
Im, Hyungsoon; Pathania, Divya; McFarland, Philip J et al. (2018) Design and clinical validation of a point-of-care device for the diagnosis of lymphoma via contrast-enhanced microholography and machine learning. Nat Biomed Eng 2:666-674
Park, Jongmin; Im, Hyungsoon; Hong, Seonki et al. (2018) Analyses of Intravesicular Exosomal Proteins Using a Nano-Plasmonic System. ACS Photonics 5:487-494
Min, Jouha; Nothing, Maria; Coble, Ben et al. (2018) Integrated Biosensor for Rapid and Point-of-Care Sepsis Diagnosis. ACS Nano 12:3378-3384
Im, Hyungsoon; Lee, Kyungheon; Weissleder, Ralph et al. (2017) Novel nanosensing technologies for exosome detection and profiling. Lab Chip 17:2892-2898