Experimental Models and Systems to Study Liver Diseases

TOPICAL COLLECTIONS

Guest Editor

Renu Dhanasekaran

Stanford University

Dr. Dhanasekaran is a physician scientist currently working at Stanford University pursuing basic and translational research in the field of hepatobiliary malignancies. Her primary research goal is to develop a deeper understanding of the molecular biology of liver cancer in order to identify diagnostic and therapeutic targets. Her lab is focused on identifying biomarkers for early detection of HCC and also evaluating novel therapeutics for liver cancer. Dr. Dhanasekaran maintains a bio-repository of tissue and blood samples from patients with liver cancer and has also developed several patient derived xenograft (PDX) models for preclinical testing. Dr. Dhanasekaran also plays an active role in the cancer genome atlas (TCGA) consortium effort to translate the knowledge gained from the study of genomics of liver cancer. She served as the manuscript coordinator for the liver cancer project of TCGA and has gained valuable experience in analyzing and interpreting complex multi-platform genomic data. The marker paper from this team-science project was published in Cell (2017). Her current translational research areas involve dissecting the role of the immune microenvironment in tumor progression in human HCC. She has recently identified immunological changes and molecular pathways involved in promoting HCC metastasis, a crucial mechanism responsible for patient mortality in HCC. Their manuscript illustrating how oncogenes drive metastasis via cytokines which orchestrate the crosstalk between tumor and host thus remodeling the immune microenvironment was published in eLife in 2020. Overall, Dr. Dhanasekaran has over 90 publications which have been cited more than 9000 times, thus reflecting the impact of her work on the field of liver diseases.

Collection Overview

The liver is the largest internal organ in the human body and it performs hundreds of complex physiological functions. Chronic liver injury from viral hepatitis, alcohol abuse, or metabolic syndrome can lead to liver inflammation, steatosis, fibrosis and liver cancer. Experimental models, in vitro and in vivo, which mimic both liver function and pathology are essential in studying liver diseases and developing therapeutics. In this Methods Collection we will review various cutting-edge models and systems that are used to study all the stages of liver diseases from steatosis to fibrosis to liver cancer. We will focus on proven models which are practical and reproducible and discuss the relative strengths and weaknesses of these models. Specifically, in this collection, we will illustrate models that experimentally induce liver fibrosis, dietary models which induce steatohepatitis, and genetically engineered mouse models of liver cancer. In vitro experimental models like organ-on-a-chip and organoid models, both of which are valuable tools during preclinical drug testing, will also be demonstrated.