Publications

Contact
1025 Walnut Street
603 College Building
Philadelphia, PA 19107
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 Carcinoma. Cancer 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 Cholangiocarcinoma. Cancer 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 Carcinoma. Scientific 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
NELFE-Dependent MYC Signature Identifies a Unique Cancer Subtype in Hepatocellular Carcinoma
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
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
Snail1 induces epithelial-to-mesenchymal transition and tumor initiating stem cell characteristics
Clinical application for the preservation of phospho-proteins through in-situ tissue stabilization
Epithelial-to-mesenchymal transition of murine liver tumor cells promotes invasion