The University of Texas Health Science Center at Houston
McGovern Medical School
Department of Anesthesiology
Research in my laboratory focuses on understanding the inflammatory mechanisms of acute and chronic liver diseases, which affect more than 30 million Americans. Although there are multiple etiologies (viral infection, drug treatment, alcohol ingestion, metabolic disorder) causing liver disease, tissue inflammation is a common central driver of the disease progression.
Macrophages are of paramount importance in both promoting inflammation/injury and tissue repair, owing to their heterogeneity and plasticity. We are interested in two specific questions: i) how does the injurious tissue microenvironment influence macrophage phenotypes, and ii) what are the molecular signaling pathways that regulate macrophage functions?
To address these questions, we employ several mouse models of liver diseases, including overdose acetaminophen (APAP)-induced acute liver injury, liver ischemia/reperfusion injury, which simulates liver transplantation/resection surgeries, and alcohol-induced chronic liver disease.
As examples of our current projects, we are investigating the role of hypoxia-inducible factors (HIFs) in mediating the hepato-protective functions of hepatic macrophages. We found that during acute liver injury caused either by overdose of APAP or ischemia, the tissue becomes hypoxic. This particular microenvironment affects the phenotypes of macrophages, which usually accumulate in hypoxic areas during tissue injury. HIF1A and HIF2A are key transcription factors regulating cellular responses to hypoxia. The studies are conducted using unique transgenic mouse lines with macrophage-specific deletion of HIF1A or HIF2A. The students will learn a multitude of in vivo and in vitro experimental methods. These include mouse handling and treatment, isolating primary cells from the mouse liver, and in vitro cell culturing. Other immunology and molecular biology experiments routinely performed in the lab include flow cytometric cell analysis, Western blot, ELISA, qPCR, cloning, etc.
Education & Training
Ph.D. - University of Toronto - 1999