Sadeesh Ramakrishnan, PhD*
W1057 Biomedical Science Tower
200 Lothrop Street
Pittsburgh, PA 15261
Tissues constantly experience a dynamic change in intracellular oxygen levels, which is influenced by both oxygen consumption and utilization. Adaptation to the changes in intracellular oxygen levels is a challenge to the tissues particularly liver, a hub of all metabolic responses. A highly conserved transcription factor, hypoxia-inducible transcription factor (HIF) orchestrates the adaptive response to low oxygen levels (hypoxia). However, chronic activation of HIF is shown to be detrimental and can lead to the numerous pathologies including fatty liver. The upstream pathways and signaling cues that are involved in the activation of HIF, independent of intracellular oxygen levels, remain unknown. Furthermore, the HIF-driven pathophysiological mechanisms that are involved in the progression of fatty liver to non-alcoholic steatohepatitis and hepatocellular carcinoma remains to be elucidated. Our research interest is to (i) investigate the mechanism by which physiological and pathological cues activate the hypoxic response in the liver, (ii) determine the role of hypoxia-mediated metabolic adaptation in fatty liver disease and liver cancer, and (iii) identify isoform specificity and therapeutic potential of HIFs in metabolic diseases and cancer.
Department of Medicine – Division of Endocrinology and Metabolism