Research Interests
Deep examinations of whole genomes in tumors highlight that the majority of DNA mutations occur
in non-coding regions. It remains unclear how their functions converge in a non-coding
regulatory network to lead to cancer. Our lab focuses on developing cutting-edge computational
and experimental approaches to uncover interactive rules within these regulatory networks, and
to understand the functional consequences of non-coding mutations through these networks. We
focus on the development of multiplexed CRISPR screening to study the functional interaction
network of enhancers. The use of this approach, combined with deep learning and statistical
modeling, will reveal the genetic code, discover novel genetic biomarkers, and develop
epistasis-aware genomic risk prediction schemes for precision cancer medicine.
Most Significant Scientific Contributions
Nested Epistasis Enhancer Networks for Robust Genome Regulation. Link.
A comprehensive analysis and resource to use CRISPR-Cas13 for broad-spectrum targeting of RNA viruses. Link.
Development of CRISPR as a prophylactic strategy to combat novel coronavirus and influenza. Link.
DNMT3A and TET1 cooperate to regulate promoter epigenetic landscapes in mouse embryonic stem cells. Link.
Sparse conserved under-methylated CpGs are associated with high-order chromatin structure. Link.
BSeQC: Quality Control of Bisulfite Sequencing Experiments. Link.
Other Publications
Multiplexed genome regulation in vivo with hyper-efficient Cas12a. Link.
The disordered N-terminal domain of DNMT3A recognizes H2AK119ub and is required for postnatal development. Link.
Broad-spectrum CRISPR-mediated inhibition of SARS-CoV-2 variants and endemic coronaviruses in vitro. Link.
Computational Methods for Analysis of Large-Scale CRISPR Screens. Link.
A benchmark of algorithms for the analysis of pooled CRISPR screens. Link.
CRISPR-mediated programmable 3D genome positioning and nuclear organization. Link.
CRISPR Activation Screens Systematically Identify Factors that Drive Neuronal Fate and Reprogramming. Link.
CRISPhieRmix: a hierarchical mixture model for CRISPR pooled screens. Link.
Homeobox oncogene activation by pan-cancer DNA hypermethylation. Link.
DNMT3A mutation leads to leukemia extramedullary infiltration mediated by TWIST1. Link.
DNMT3A loss drives enhancer hypomethylation in FLT3-ITD-associated leukemias. Link.
Broad H3K4me3 is associated with increased transcription elongation and enhancer activity at tumor-suppressor genes. Link.
Comparative analysis of metazoan chromatin organization. Link.
PHF8 and REST/NRSF co-occupy gene promoters to regulate proximal gene expression. Link.
CistromeFinder for ChIP-seq and DNase-seq data reuse. Link.
Software & Code
SRE_Predictor
BSeQC
CRISPhieRmix
EnhancerNet
PACMAN