Liver Immunology and Metabolism

Lab head: Jacob George and Saeed Esmaili
Location: Westmead Institute for Medical Research

Australia is among the countries with the fastest growing rates of overweight and obesity, which by 2025 will affect >70% of the population. Chronic diseases linked to obesity include type 2 diabetes, cardiovascular disease, cancer and fatty liver. In all these diseases, the metabolic milieu is characterized by low-grade inflammation that is ultimately modulated by nutrient intake. Macrophages play a pivotal role in this obesity-mediated inflammation. Our recent work suggests that cholesterol in the diet can change the homeostasis of hematopoietic stem cells and progenitor cells (HSPCs) in the bone marrow. These cells can we believe, subsequently differentiate to inflammatory cells with subsequent secretion of cytokines required for cancer cell growth. This project will investigate the mechanisms by which the cholesterol content of the diet affects the function of the bone marrow stem cell that eventually leads to liver inflammation and cancer. The study will involve multi-color flow cytometric detection of progenitor and inflammatory cells in different organs, and will also be suitable for an Honors project or PhD studies.

Lab members: Saeed Esmaili, 2 Post Docs, 3 Phd students, 1 Masters student
Funding: Robert W. Storr Bequest, NHMRC Program and Project grants
Research approach equipment: Full state of the art facilities available at WIMR

Career record of 348 publications and citation index of >25,000

Exploring the role of epigenetic factors modulating the predisposition to tissue scarring (fibrosis) and cancer

Primary supervisor: Jacob George

PhD or Masters or Honours

To date, most studies of genetic variation between individuals that contribute to tissue scarring and to cancer have focused on single nucleotide polymorphisms (SNPs), the most common type of genetic variation. However, SNPs explain only a small percentage of the heritability of complex diseases (4), explaining ~20% of heritability. This suggests that other variants and types of genetic variation remain to be discovered. Epigenetics is likely a major player in defining missing heritability, but the precise details are yet to be dissected. In this project, we will investigate the role of epigenetics in tissue scarring/fibrosis. The project will involve working with human samples. 

Discipline: Applied Medical Sciences, Westmead
Keywords: Epigenetics, Genomics, Liver fibrosis