Chronic Liver Disease
Alex B. Lentsch, PhD
Professor and Vice Chairman for Research
Department of Surgery
Description of Research
Dr. Lentsch investigates the intricate roles of various soluble mediators in the initiation and regulation of the acute inflammatory response to hepatic ischemia/reperfusion, and how these factors are modulated by postnatal development and age. He has recently shown that the response to injury by the liver and the immune systems differs substantially in young versus adult mice. These age-related responses are linked to altered activation of NF-kB in hepatocytes. Dr. Lentsch’s laboratory has shown that two important changes in NF-kB occur with increased mouse age. First, the expression of specific subunits of the proteasome changes in older mice. Second, activation of the intracellular kinase Akt is reduced with age. These change lead to a suppression of NF-kB activation in hepatocytes, increased cell death, and liver dysfunction. Furthermore, Dr. Lentsch’s work has shown that some key cytoprotective proteins, such as the heat shock protein-70 (HSP70), are induced to a much lesser extent after ischemia/reperfusion in the livers of old mice compared to young mice. Thus, the divergence in the injury response due to age is related to selective, age-dependent activation of NF-kB and other molecular circuits.
Collaborations and Core Use
Dr. Lentsch collaborates with Drs. Zingarelli and Pritts investigating the molecular and cellular mechanisms of the immune response to ischemia/reperfusion liver injury. Projection of Core use: Gene and Protein Expression, Bioinformatics, and Integrative Morphology Cores.
