Publications

Hien Dang

Contact

Name: Hien Dang, PhD
Position: Assistant Professor

1025 Walnut Street
603 College Building
Philadelphia, PA 19107

Telephone: 215-955-1621

Highlighted Publications

Barry AE, Baldeosingh R, Lamm R, et al (2020) Hepatic Stellate Cells and Hepatocarcinogenesis. Front. Cell Dev. Biol., 8(709). 

 https://doi.org/10.3389/fcell.2020.00709

    Hepatic stellate cells (HSCs) are a significant component of the hepatocellular       carcinoma (HCC) tumor microenvironment (TME). Activated HSCs transform     into myofibroblast-like cells to promote fibrosis in response to liver injury or        chronic inflammation, leading to cirrhosis and HCC. The hepatic TME is     comprised of cellular components, including activated HSCs, tumor-associated     macrophages, endothelial cells, immune cells, and non-cellular components,     such as growth factors, proteolytic enzymes and their inhibitors, and other     extracellular matrix (ECM) proteins. Interactions between HCC cells and their     microenvironment have become topics under active investigation. These     interactions within the hepatic TME have the potential to drive carcinogenesis     and create challenges in generating effective therapies. Current studies reveal     potential mechanisms through which activated HSCs drive        hepatocarcinogenesis utilizing matricellular proteins and paracrine crosstalk     within the TME. Since activated HSCs are primary secretors of ECM proteins     during liver injury and inflammation, they help promote fibrogenesis, infiltrate     the HCC stroma, and contribute to HCC development. In this review, we     examine several recent studies revealing the roles of HSCs and their clinical     implications in the development of fibrosis and cirrhosis within the hepatic     TME.

Zhang K, Pomyen Y, Barry AE, et al. AGO2 Mediates MYC mRNA Stability in Hepatocellular Carcinoma [published online ahead of print, 2020 Jan 15]. Mol Cancer 

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 an oncogenic RBP that can regulate the MYC transcript in a RISC-independent manner to promote HCC. By utilizing transcriptomics, we show that activated AGO2 preferentially affects MYC mRNAs by enhancing their stability. We’re now elucidating how AGO2 promotes HCC progression by directly interacting with many mRNA targets independent of miRNAs.

Dang, H et al (2017) Oncogenic Activation of the RNA Binding Protein NELFE and MYC Signaling in Hepatocellular CarcinomaCancer Cell, 32, 101-114.

Tumor initiation and maintenance require the selection of a unique tumor-promoting transcriptome induced by driver genes. Our study indicates that RNA binding proteins can mediate cancer-associated transcriptomic changes in hepatocellular carcinoma (HCC). Our work is consistent with the hypotheses that NELFE activation drives hepatocarcinogenesis and that the NELFE-MYC axis may be exploited as a viable therapeutic target for HCC.

Chaisaingmongkol, J et al (2017) Common Molecular Subtypes Among Asian Hepatocellular Carcinoma and CholangiocarcinomaCancer Cell, 32, 57-70

Primary liver cancers have a complex mutational landscape with vast inter-tumor heterogeneity, which poses a major challenge to define actionable drivers. Here, we demonstrate that common molecular subtypes with key drivers are shared among Asian ICC andHCC patients through systematic integration of the genome, transcriptome, and metabolome. Our results indicate thatICC and HCC, while clinically treated as separate entities, share common molecular determinants, suggesting that a unifiedmolecular landscape of liver cancer is required to improve diagnosis and therapy.

Dang, H et al (2019) NELFE-Dependent MYC Signature Identifes a Unique Cancer Subtype in Hepatocellular CarcinomaScientific Reports, 9:3369.

We identified a gene signature to predict a unique subtype of HCC, which is associated with a poor prognosis in three independent cohorts encompassing diverse etiologies, demographics, and viral status. The application of our genes signature offers patients access to personalized risk assessments, which may be utilized to direct future care.

Recent Publications

Depletion of TRRAP Induces p53-Independent Senescence in Liver Cancer by Down-Regulating Mitotic Genes

NELFE-Dependent MYC Signature Identifies a Unique Cancer Subtype in Hepatocellular Carcinoma

Genome-wide RNAi screen identifies PMPCB as a therapeutic vulnerability in EpCAM+ hepatocellular carcinoma

Erratum to: Necroptosis microenvironment directs lineage commitment in liver cancer (Nature, (2018), 562, 7725, (69-75), 10.1038/s41586-018-0519-y)

Non-proteolytic ubiquitin modification of PPARγ by Smurf1 protects the liver from steatosis

Necroptosis microenvironment directs lineage commitment in liver cancer

Single-cell analysis reveals cancer stem cell heterogeneity in hepatocellular carcinoma

The significance of intertumor and intratumor heterogeneity in liver cancer

Ubiquitin-specific protease 21 stabilizes BRCA2 to control DNA repair and tumor growth

Oncogenic Activation of the RNA Binding Protein NELFE and MYC Signaling in Hepatocellular Carcinoma

Common Molecular Subtypes Among Asian Hepatocellular Carcinoma and Cholangiocarcinoma

Cancer exosomes: Wanted by many, explored by few, waiting for one

Three-dimensional Organotypic Culture Models of Human Hepatocellular Carcinoma

LTβR signalling preferentially accelerates oncogenic AKT-initiated liver tumours

Hepatic stellate cell and monocyte interaction contributes to poor prognosis in hepatocellular carcinoma

The EGFR/ErbB3 pathway acts as a compensatory survival mechanism upon c-Met inhibition in human c-Met+ hepatocellular carcinoma

Induction of tumor initiation is dependent on CD44s in c-Met+ hepatocellular carcinoma

Identification of drivers from cancer genome diversity in hepatocellular carcinoma

The origin of cancer stem cells

MiR-200b restoration and DNA methyltransferase inhibitor block lung metastasis of mesenchymal-phenotype hepatocellular carcinoma

Snail1 induces epithelial-to-mesenchymal transition and tumor initiating stem cell characteristics

c-Met represents a potential therapeutic target for personalized treatment in hepatocellular carcinoma

Clinical application for the preservation of phospho-proteins through in-situ tissue stabilization

Epithelial-to-mesenchymal transition of murine liver tumor cells promotes invasion

Expansion of hepatic tumor progenitor cells in pten-null mice requires liver injury and is reversed by loss of AKT2