David A. Geller, MD
Dr. Geller is the Richard L. Simmons Professor of Surgery at the University of Pittsburgh School of Medicine, and Co-Director of the UPMC Liver Cancer Center. As a liver transplant and hepatobiliary surgeon, his clinical practice centers on the evaluation and management of patients with liver cancers. His research interests focus on transcriptional regulation of the human iNOS gene, as well as molecular mechanisms of hepatic I/R injury. His team cloned the human iNOS gene, and has spent the past decade studying the transcriptional factors that regulate human iNOS gene expression in response to inflammatory cytokines. His group identified NF-kB repressing factor (NRF) as a negative transcription factor that constitutively silences the human iNOS gene by binding to an upstream cis-acting NRE response element. Recently, his group also showed that the human iNOS gene is a target of Wnt/B-catenin signaling pathway in human cancer cells. The significance is the novel mechanism where B-catenin may contribute to cancer by inducing iNOS expression and NO production. In related translational research, his laboratory is also studying the role of L-arginine, NO, and iNOS in liver ischemia/reperfusion injury. They have shown that blockade of the L-arginine/NOS pathway worsens liver damage during liver transplant preservation injury. They noted that liver transplant recipients are profoundly arginine-deficient due to hepatocellular arginase release and are currently pursuing novel strategies to inhibit arginase activity to augment arginine and NO to ameliorate liver ischemia/reperfusion injury.