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.

Public Health Relevance

Aberrant patterns in the epigenomic landscape have been closely associated with cancer. We will develop the next-generation MOWChIP-seq (microfluidic-oscillatory-washing-based ChIP- seq) technology for mapping epigenomes with low input and high throughput.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants Phase II (R33)
Project #
5R33CA214176-02
Application #
9488455
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Divi, Rao L
Project Start
2017-05-23
Project End
2020-03-31
Budget Start
2018-04-01
Budget End
2019-03-31
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Virginia Polytechnic Institute and State University
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
003137015
City
Blacksburg
State
VA
Country
United States
Zip Code
24061