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Grant Details

Grant Number: 5R33CA214176-03 Interpret this number
Primary Investigator: Lu, Chang
Organization: Virginia Polytechnic Inst And St Univ
Project Title: Next-Generation Mowchip-Seq for High-Throughput Epigenomic Profiling Using Clinically Relevant Samples
Fiscal Year: 2019


Project Summary Aberrant patterns in the epigenomic landscape have been closely associated with cancer. Deregulation of histone modifications silences tumor-suppressor genes, triggers genetic changes via aberrant DNA repair/replication, and contributes to tumor heterogeneity. Chromatin immunoprecipitation (ChIP) assay is the technique of choice for examining epigenetic mechanisms in vivo such as histone modifications. However, the technique in its conventional form suffers from serious limitations. The prevailing ChIP-seq protocol requires 107 cells per test, involves extensive manual handling of the samples, and takes 3-4 days to generate a sequencing library. The requirement of a large sample amount practically prevents the use of ChIP-seq on samples from scarce sources such as animal models and patients. We recently demonstrated a microfluidic technology (microfluidic-oscillatory-washing-based ChIP-seq or MOWChIP-seq) for profiling genome-wide histone modifications using as few as 100 cells. In this R33 project, we will develop the next-generation MOWChIP-seq technology by facilitating high throughput, improving the level of integration, and further validating the technology via testing mouse and human samples. The development will fully validate the use of MOWChIP- seq for high-throughput epigenomic profiling of a large number of samples in clinical research settings.


Multiplexed and Ultralow-Input ChIP-seq Enabled by Tagmentation-Based Indexing and Facile Microfluidics.
Authors: Deng C. , Murphy T.W. , Zhang Q. , Naler L.B. , Xu A. , Lu C. .
Source: Analytical chemistry, 2020-10-20; 92(20), p. 13661-13666.
EPub date: 2020-10-01.
PMID: 32957776
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Microfluidic Platform for Next-Generation Sequencing Library Preparation with Low-Input Samples.
Authors: Murphy T.W. , Hsieh Y.P. , Zhu B. , Naler L.B. , Lu C. .
Source: Analytical chemistry, 2020-02-04; 92(3), p. 2519-2526.
EPub date: 2020-01-14.
PMID: 31894965
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MOWChIP-seq for low-input and multiplexed profiling of genome-wide histone modifications.
Authors: Zhu B. , Hsieh Y.P. , Murphy T.W. , Zhang Q. , Naler L.B. , Lu C. .
Source: Nature protocols, 2019 Dec; 14(12), p. 3366-3394.
EPub date: 2019-10-30.
PMID: 31666743
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Microfluidic epigenomic mapping technologies for precision medicine.
Authors: Deng C. , Naler L.B. , Lu C. .
Source: Lab on a chip, 2019-08-21; 19(16), p. 2630-2650.
EPub date: 2019-07-24.
PMID: 31338502
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BRCA1 mutations attenuate super-enhancer function and chromatin looping in haploinsufficient human breast epithelial cells.
Authors: Zhang X. , Wang Y. , Chiang H.C. , Hsieh Y.P. , Lu C. , Park B.H. , Jatoi I. , Jin V.X. , Hu Y. , Li R. .
Source: Breast cancer research : BCR, 2019-04-17; 21(1), p. 51.
EPub date: 2019-04-17.
PMID: 30995943
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A diffusion-based microfluidic device for single-cell RNA-seq.
Authors: Sarma M. , Lee J. , Ma S. , Li S. , Lu C. .
Source: Lab on a chip, 2019-03-27; 19(7), p. 1247-1256.
PMID: 30815639
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Effects of culture condition on epigenomic profiles of brain tumor cells.
Authors: Cox M.C. , Deng C. , Naler L.B. , Lu C. , Verbridge S.S. .
Source: ACS biomaterials science & engineering, 2019-03-11; 5(3), p. 1544-1552.
EPub date: 2019-02-07.
PMID: 31799379
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Microfluidic MeDIP-seq for low-input methylomic analysis of mammary tumorigenesis in mice.
Authors: Zhu Y. , Cao Z. , Lu C. .
Source: The Analyst, 2019-03-11; 144(6), p. 1904-1915.
PMID: 30631869
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Microfluidic Low-Input Fluidized-Bed Enabled ChIP-seq Device for Automated and Parallel Analysis of Histone Modifications.
Authors: Murphy T.W. , Hsieh Y.P. , Ma S. , Zhu Y. , Lu C. .
Source: Analytical chemistry, 2018-06-19; 90(12), p. 7666-7674.
EPub date: 2018-06-08.
PMID: 29842781
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Low-input and multiplexed microfluidic assay reveals epigenomic variation across cerebellum and prefrontal cortex.
Authors: Ma S. , Hsieh Y.P. , Ma J. , Lu C. .
Source: Science advances, 2018 Apr; 4(4), p. eaar8187.
EPub date: 2018-04-18.
PMID: 29675472
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Microfluidics-Based Chromosome Conformation Capture (3C) Technology for Examining Chromatin Organization with a Low Quantity of Cells.
Authors: Sun C. , Lu C. .
Source: Analytical chemistry, 2018-03-20; 90(6), p. 3714-3719.
EPub date: 2018-03-08.
PMID: 29498513
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Recent advances in the use of microfluidic technologies for single cell analysis.
Authors: Murphy T.W. , Zhang Q. , Naler L.B. , Ma S. , Lu C. .
Source: The Analyst, 2017-12-18; 143(1), p. 60-80.
PMID: 29170786
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