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 |
Abstract
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.
Publications
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 00:00:00.0; 92(20), p. 13661-13666.
EPub date: 2020-10-01 00:00:00.0.
PMID: 32957776
Related Citations
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 00:00:00.0; 92(3), p. 2519-2526.
EPub date: 2020-01-14 00:00:00.0.
PMID: 31894965
Related Citations
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, 2019-10-30 00:00:00.0; , .
EPub date: 2019-10-30 00:00:00.0.
PMID: 31666743
Related Citations
Microfluidic epigenomic mapping technologies for precision medicine.
Authors: Deng C.
, Naler L.B.
, Lu C.
.
Source: Lab On A Chip, 2019-08-21 00:00:00.0; 19(16), p. 2630-2650.
EPub date: 2019-07-24 00:00:00.0.
PMID: 31338502
Related Citations
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 00:00:00.0; 21(1), p. 51.
EPub date: 2019-04-17 00:00:00.0.
PMID: 30995943
Related Citations
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 00:00:00.0; 19(7), p. 1247-1256.
PMID: 30815639
Related Citations
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 00:00:00.0; 144(6), p. 1904-1915.
PMID: 30631869
Related Citations
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 00:00:00.0; 5(3), p. 1544-1552.
EPub date: 2019-02-07 00:00:00.0.
PMID: 31799379
Related Citations
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 00:00:00.0; 90(12), p. 7666-7674.
EPub date: 2018-06-08 00:00:00.0.
PMID: 29842781
Related Citations
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 00:00:00.0.
PMID: 29675472
Related Citations
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, 2018-03-08 00:00:00.0; , .
EPub date: 2018-03-08 00:00:00.0.
PMID: 29498513
Related Citations
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 00:00:00.0; 143(1), p. 60-80.
PMID: 29170786
Related Citations