The Dang lab studies the role of RNA binding proteins in primary liver cancer. Our goal is to identify unique drivers of liver cancer to develop novel biomarkers or therapies to improve patient outcome. The lab has several areas of expertise, including RNA biology, translational, bioinformatics, and molecular biology to identify key oncogenic RBPs involved in transcriptomic alterations associated with disease states.
Integrative Functional Genomics
We are interested in utilizing several areas of RNA biology, translational, bioinformatics, and molecular biology to identify key oncogenic RBPs involved in transcriptomic alterations associated with disease states. For example, we have recently identified Argonaute 2 (AGO2) as a possible oncogenic RBP that can promote an HCC transcriptome in a RISC-independent manner. By utilizing transcriptomics, we are modeling how activated AGO2 preferentially affects mRNAs by enhancing their stability in HCCs driven by AGO2. We’re now elucidating how AGO2 promotes HCC progression by directly interacting with mRNA targets independent of miRNAs.
The central focus of our research is investigating the dysregulation of mRNA binding proteins (mRBPs) in hepatocellular carcinoma (HCC). Our recent work identified Negative Elongation Factor E (NELFE) as an oncogenic RBP that is associated with poor clinical outcome in more than 1200 clinical specimens. We identified the novel mechanisms in which NELFE enhances the oncogene MYC to promote tumorigenesis. We are currently interested in how NELFE interact with and regulate their RNA targets through modular domains such as low complexity sequences (LCS) and RNA recognition motifs (RRMs).Title Placeholder
Tumor heterogeneity represents a significant barrier to improving HCC patient outcomes and poses a challenge for the establishment of robust HCC classification, making treatment extremely difficult. Consequently, the ability to discriminate patients with greater homogeneity and clinically relevant therapeutic targets will help guide treatments to improve patient outcome. We have developed a robust 20-NELFE dependent MYC (NDMPOS) gene signature, which reflects the biological characteristics of HCC. We are interested in utilizing genome-wide CRISPR/Cas9 screens to identify therapeutics for this specific subtype. In collaboration with others, we have developed a MYC-induced NELFE HCC Sleeping Beauty mouse model (Trp53flox/flox; Alb-Cre) and in vitro cell models, such as patient derived cell lines that can be used to validate targets.