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Shao, Huilin

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Shao

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Huilin

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Shao, Huilin

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2012 - 20164

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Author's Publications: search.filters.isAuthorOfPublication.d17b9c6a-031c-4092-9f79-e528a98f9268

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Now showing 1 - 4 of 4
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    Biosensor Platforms for Molecular Analyses of Circulating Cancer Biomarkers
    (2013-10-15) Shao, Huilin; Weissleder, Ralph; Langer, Robert S.; Breakefield, Xandra; Lee, Hakho; Westervelt, Robert; Hogle, James
    Solid cancers often shed (sub)cellular materials into the circulation, such as circulating tumor cells and extracellular microvesicles. Mounting evidence supports that these circulating materials could serve as surrogate cancer markers for classifying primary tumors, stratifying patients for targeted therapies, assessing treatment efficacy, and achieving clinical benefits. A sensor platform capable of sensitive and portable detection of circulating cancer markers would thus be an invaluable tool, that will advance our understanding of tumor biology as well as clinical outcomes. This dissertation describes various systems that we have developed for quantitative analyses of circulating cancer biomarkers. Firstly, we have developed a novel magnetic resonance sensing platform for microvesicle analyses. By using a chip-based platform that combines microfiltration and bioorthogonal nanoparticle targeting, we demonstrate for the first time that magnetic biosensing can be applied for clinical evaluation of circulating microvesicles in blood samples to monitor cancer therapy. Secondly, we have advanced a new plasmonic sensor to achieve label-free detection of microvesicles. Based on periodic nanohole arrays, this platform has been applied for high-throughput protein profiling of microvesicles in native ascites. Finally, we have implemented microfluidic devices to effectively enrich circulating tumor cells from peripheral whole blood, and to enable comprehensive molecular analyses of isolated tumor cells at a single cell resolution. By enabling rapid, sensitive and cost-effective detection of circulating cancer markers, these developed platforms could significantly expand the reach of preclinical and clinical cancer research, in informing therapy selection, rationally directing trials, and improving sequential monitoring to achieve better clinical outcomes.
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    Chip-based analysis of exosomal mRNA mediating drug resistance in glioblastoma
    (Nature Pub. Group, 2015) Shao, Huilin; Chung, Jaehoon; Lee, Kyungheon; Balaj, Leonora; Min, Changwook; Carter, Bob S.; Hochberg, Fred H.; Breakefield, Xandra; Lee, Hakho; Weissleder, Ralph
    Real-time monitoring of drug efficacy in glioblastoma multiforme (GBM) is a major clinical problem as serial re-biopsy of primary tumours is often not a clinical option. MGMT (O6-methylguanine DNA methyltransferase) and APNG (alkylpurine-DNA-N-glycosylase) are key enzymes capable of repairing temozolomide-induced DNA damages and their levels in tissue are inversely related to treatment efficacy. Yet, serial clinical analysis remains difficult, and, when done, primarily relies on promoter methylation studies of tumour biopsy material at the time of initial surgery. Here we present a microfluidic chip to analyse mRNA levels of MGMT and APNG in enriched tumour exosomes obtained from blood. We show that exosomal mRNA levels of these enzymes correlate well with levels found in parental cells and that levels change considerably during treatment of seven patients. We propose that if validated on a larger cohort of patients, the method may be used to predict drug response in GBM patients.
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    Diagnostic technologies for circulating tumour cells and exosomes
    (Portland Press Ltd., 2016) Shao, Huilin; Chung, Jaehoon; Issadore, David
    Circulating tumour cells (CTCs) and exosomes are promising circulating biomarkers. They exist in easily accessible blood and carry large diversity of molecular information. As such, they can be easily and repeatedly obtained for minimally invasive cancer diagnosis and monitoring. Because of their intrinsic differences in counts, size and molecular contents, CTCs and exosomes pose unique sets of technical challenges for clinical translation–CTCs are rare whereas exosomes are small. Novel technologies are underway to overcome these specific challenges to fully harness the clinical potential of these circulating biomarkers. Herein, we will overview the characteristics of CTCs and exosomes as valuable circulating biomarkers and their associated technical challenges for clinical adaptation. Specifically, we will describe emerging technologies that have been developed to address these technical obstacles and the unique clinical opportunities enabled by technological innovations.
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    Magnetic Nanoparticles and MicroNMR for Diagnostic Applications
    (Ivyspring International Publisher, 2012) Shao, Huilin; Min, Changwook; Issadore, David; Liong, Monty; Yoon, Tae-Jong; Weissleder, Ralph; Lee, Hakho
    Sensitive and quantitative measurements of clinically relevant protein biomarkers, pathogens and cells in biological samples would be invaluable for disease diagnosis, monitoring of malignancy, and for evaluating therapy efficacy. Biosensing strategies using magnetic nanoparticles (MNPs) have recently received considerable attention, since they offer unique advantages over traditional detection methods. Specifically, because biological samples have negligible magnetic background, MNPs can be used to obtain highly sensitive measurements in minimally processed samples. This review focuses on the use of MNPs for in vitro detection of cellular biomarkers based on nuclear magnetic resonance (NMR) effects. This detection platform, termed diagnostic magnetic resonance (DMR), exploits MNPs as proximity sensors to modulate the spin-spin relaxation time of water molecules surrounding the molecularly-targeted nanoparticles. With new developments such as more effective MNP biosensors, advanced conjugational strategies, and highly sensitive miniaturized NMR systems, the DMR detection capabilities have been considerably improved. These developments have also enabled parallel and rapid measurements from small sample volumes and on a wide range of targets, including whole cells, proteins, DNA/mRNA, metabolites, drugs, viruses and bacteria. The DMR platform thus makes a robust and easy-to-use sensor system with broad applications in biomedicine, as well as clinical utility in point-of-care settings.