Hong Lu, PhD

Research Abstract

Liver is vital for the survival of the organism due to its critical role in nutrition and detoxification of xenobiotics and metabolic wastes. The major research interest of my laboratory is to understand the roles of nuclear receptors (transcription factors) and epigenetics in regulating gene expression during liver development and carcinogenesis so that we can develop more effective and safer drug treatment for patients.  We have 3 closely related major research projects.

Nuclear receptors and epigenetics in developmental regulation of drug processing genes. Children are more susceptible to adverse effects of drugs and environmental chemicals due to their immature capacity of processing xenobiotics. The major purpose of this project is to understand the roles of nuclear receptors and epigenetics in developmental regulation of drug processing genes.  We are using RNA-sequencing to elucidate changes of transcriptome in livers of wild-type and knockout mice during development.  We are using ChIP-sequencing to study dynamic changes of epigenome (DNA methylation and histone modifications) and global DNA-binding of transcription factors during liver development.   Additionally, to bridge the huge gap of species difference in the translation of scientific findings from animals to humans, we are establishing a novel 3D co-culture model of hepatocyte maturation to use in vitro model to mimic the in vivo developmental regulation of drug processing genes in mice and humans.

Epigenetics in liver carcinogenesis. Epigenetics is not only essential in liver development, but also liver carcinogenesis.  Histone methyltransferases G9a and EZH2 are two key epigenetic enzymes responsible for epigenetic silencing of gene expression.  G9a and EZH2 are overexpressed in human liver cancer.  My laboratory is using conditional double knockin/knockout mouse models to study the roles of these two key epigenetic enzymes in liver carcinogenesis.

G-quadruplex in translational regulation and cancer therapy. Different from many other major cancers, primary liver cancer is the direct cause of death because liver is vital for the survival of the organism. Liver cancer is intrinsically resistant to cytotoxic drugs, and most liver cancer patients have markedly compromised liver function due to liver fibrosis/cirrhosis.  Therefore, an ideal therapy for liver cancer should treat liver cancer and improve liver function simultaneously.  My laboratory is actively studying how the protein expression of certain liver-enriched transcription factors is regulated by a special nucleic acid structure, G-quadruplex (G4).  Meanwhile, we are studying the anticancer mechanism of G4 DNA oligos. The long-term goal of this study is to develop novel therapy to treat liver cancer and improve liver function simultaneously, through restoring the protein expression and activity of master regulators of liver development and liver function.