| 项目编号: | 1509713
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| 项目名称: | UNS:Direct measurement of DUB activity in intact single cells using a droplet microfluidic array |
| 作者: | Adam Melvin
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| 承担单位: | Louisiana State University & Agricultural and Mechanical College
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| 批准年: | 2014
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| 开始日期: | 2015-06-15
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| 结束日期: | 2018-05-31
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| 资助金额: | USD313643
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| 资助来源: | US-NSF
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| 项目类别: | Standard Grant
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| 国家: | US
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| 语种: | 英语
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| 特色学科分类: | Engineering - Chemical, Bioengineering, Environmental, and Transport Systems
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| 英文关键词: | dub activity
; dub-specific
; intact single cell
; microfluidic droplet array
; proposal
; myeloma cell
; dub-specific fluorescent reporter
; drug-resistant cell
; drug
; cancer cell
; bulk measurement
; dub-targeted therapy
; dub-specific substrate
; potent cell
|
| 英文摘要: | 1509713
Melvin, Adam
One of the greatest challenges facing myeloma patients is the resistance to the drugs currently used to treat the disease. This interdisciplinary project involves the development of a microfluidic device and man-made peptide-based biosensors to specifically identify distinct sub-populations of cancer cells found in a tumor, including those that are resistant to particular chemotherapy drugs. Ultimately, the goal of this proposal is to develop a new diagnostic tool that can lead to a personalized treatment protocol for high risk myeloma patients, dramatically increasing the prognosis of individuals battling cancer.
Molecularly-targeted therapeutics and personalized medicine have dramatically increased the prognosis of patients suffering from cancer. In the case of multiple myeloma, there has been great success using drugs that specifically target enzymes associated with the ubiquitin proteasome system (UPS). Deubiquitinating enzymes (DUBs) are one such class of enzyme due to their ability to promote drug resistance in multiple myeloma patients. In this proposal, an interdisciplinary approach will be applied to develop a new method to directly measure DUB activity in intact single cells across a heterogeneous population such as tumor biopsy. A long-lived, cell permeable, DUB-specific fluorescent reporter will be developed to directly measure DUB activity. One hallmark of this peptide-based reporter is the inclusion of a â-hairpin ?protectide?, serving to both confer stability onto the DUB-specific substrate, and to act as a potent cell penetrating peptide (CPP). This novel reporting scheme will be incorporated into a microfluidic droplet array that will be developed to facilitate high-throughput screening (HTS) of a population of myeloma cells. The microfluidic droplet array designed in this proposal will allow for on-chip encapsulation followed by real-time quantification of DUB activity in intact single cells. The biochemical assay will serve as a first step in developing a new technique allowing to 1) determine if patients would benefit from a DUB-targeted therapy, 2) identify an ideal dose of drug to maximize efficacy while minimizing side effects, and 3) analyze a heterogeneous sample to identify distinct subpopulations of drug-resistant cells, which cannot be performed using bulk measurement.
This award by the Biotechnology and Biochemical Engineering Program of the CBET Division is co-funded by the Experimental Program to Stimulate Competitive Research (EPSCoR). |
| 资源类型: | 项目
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| 标识符: | http://119.78.100.158/handle/2HF3EXSE/94407
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| Appears in Collections: | 影响、适应和脆弱性
气候减缓与适应
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| Recommended Citation: | |
Adam Melvin. UNS:Direct measurement of DUB activity in intact single cells using a droplet microfluidic array. 2014-01-01.
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