Ph.D., University of Toledo Health Science Campus, 2005
The major goal of our research program is to determine the molecular mechanisms by which oxygen sensing transcription factors regulate gastrointestinal homeostasis, inflammation and cancer. Cellular oxygen level is an important systemic signal that modulates metabolic activities and disease in the liver and intestine. Low cellular oxygen also referred to as hypoxia is observed in several gastrointestinal diseases such as non-alcoholic and alcoholic fatty liver disease, inflammatory bowel disease and liver and colon cancers. Regulation of hypoxia-mediated genes is dependent on the nuclear transcription factor, hypoxia inducible factor (HIF). HIF signaling is critical in the adaptive response to low oxygen levels by activating genes involved in metabolism, angiogenesis, cell survival and iron metabolism. Using the latest in mouse transgenic technology we have developed novel animal models to study accurately the role of oxygen sensitive transcription factors in the liver and intestine. These studies have revealed new pathways that have not previously been associated with hypoxia.