Research Abstract:
Liver-to-body weight ratio is tightly regulated during normal development and precisely restored by hepatic regeneration after injury. The objective of Dr. Rudnick's research program is to elucidate the molecular signaling mechanisms that underlie this precise regulation and remarkable regenerative potential of liver mass. Dr. Rudnick's laboratory employs the rodent partial hepatectomy model system to investigate liver regeneration in genetically- and pharmacologically-manipulated mouse models. Using this strategy, he has characterized critical roles for COX-2 derived prostaglandin signaling and Egr-1 expression during normal liver regeneration. Recently, he has used genomic analysis of regenerating liver to identify a novel genetic program associated with liver regeneration. This analysis led to the identification of a pattern of adipogenic gene expression induced coincident with transient marked hepatic fat accumulation during liver regeneration. Disruption of this adipogenic program resulted in impaired liver regeneration, suggesting that these adipogenic changes or the signals that regulate them are necessary for normal liver regeneration. Several lines of investigation based on these observations are underway in order to further characterize the molecular regulatory mechanisms and specific functional roles of hepatic adipogenic changes during normal liver regeneration. Ultimately, these efforts should lead to new insight into hepatobiliary organogenesis and the pathogenesis of liver diseases, and may also lead to the development of novel diagnostic and therapeutic tools for management of acute and chronic liver diseases.
Selected Publications:
Rudnick DA. Trimming the fat from liver regeneration. Hepatology 2005 42:1001-1003.
Liao Y, Shikapwashya O, Shteyer E, Dieckgraefe BK, et al. Delayed hepatocellular mitotic progression and impaired liver regeneration in early-growh-response-1 deficient mice. J Biol Chem 2004 41:43107-43116.
Rudnick DA, Perlmutter DH, Muglia LJ, et al. Analyses of hepatocellular proliferation in a mouse model of Alpha-1-Antitrypsin deficiency. Hepatology 2004 39:1048-1055.
Shteyer E, Liao Y, Muglia LJ, et al. Disruption of hepatic adipogenesis is associated with impaired liver regeneration. Hepatology 2004 40:1322-1332.
Rudnick DA, Perlmutter DH, Muglia LJ. Prostaglandins are required for CREB activation and cellular proliferation during liver regeneration. Proc Natl Acad Sci USA 2001 98:8885-8890.
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