David A. Rudnick, M.D., Ph.D.

Associate Professor
Gastroenterology & Nutrition
Developmental Biology

Developmental, Regenerative and Stem Cell Biology Program

Research Abstract:

My laboratory is interested in understanding the mechanisms that regulate the ability of the liver to regenerate, and in using that knowledge to develop improved strategies for diagnosing and treating children with liver diseases. The remarkable regenerative potential of this organ, which has been recognized for millenia as recounted in the ancient Greek mythology legend of Prometheus, permits structural and functional recovery from the deficits that follow hepatic injury. The best characterized experimental system for studying liver regeneration is the rodent partial hepatectomy model, which has been used for almost the last century to investigate the physiological, cellular, and molecular processes that occur during and are responsible for this process. Analyses using this system have led to the identification of many signals that are regulated during and necessary for normal liver regeneration. For example, the early response to partial hepatectomy is characterized by induction of specific growth factor- and cytokine-dependent signaling and transcription factor activation. These events direct an immediate-early gene expression program which promotes normally quiescent hepatocytes to re-enter and progress through the cell cycle. Ultimately this leads to restoration of normal hepatic mass. Despite this knowledge, an integrated understanding of the precise mechanistic regulation of the hepatic regenerative response remains incomplete. Indeed, the nature and identities of the most proximal and distal signals that initiate and terminate hepatic regeneration are still largely unknown.

In our lab, we employ the partial hepatectomy model in pharmacologically and genetically manipulated mouse models, together with modern genomic, proteomic, and metabolomic analytical platforms, to further characterize the signals required for a normal hepatic regenerative response. Our hope is that elucidating these pathways will provide insight into hepatic growth regulation in health and disease, and lead to the development of novel diagnostic or therapeutic strategies for treating, preventing, or reversing the complications of acute and chronic liver diseases. Our studies may also provide a paradigm for analyses of regeneration in other tissues.

Selected Publications:

Rudnick DA, Dietzen DJ, Turmelle Y, Shepherd R, Zhang S, Belle S, Squires R, and the Pediatric Acute Liver Failure Study Group. Serum a-NH2-Butyric Acid May Predict Spontaneous Survival in Pediatric Acute Liver Failure. Pediatric Transplantation 2009 13:223-230.

Weymann A, Hartman E, Gazit V, Wang C, Glauber M, Turmelle Y, and Rudnick DA. p21 is Required for Dextrose-Mediated Inhibition of Mouse Liver Regeneration. Hepatology 2009 50:207-215.

Rudnick DA, Shikapwashya O, Blomenkamp K, and Teckman JH. NSAIDs Increase Liver Injury in a Murine Model of Alpha-1-Antritrypsin Deficiency. Hepatology 2006 44: 976-982.

Shteyer E, Liao Y, Muglia LJ, Hruz P, Rudnick DA. Disruption of Hepatic Adipogenesis is Associated with Impaired Liver Regeneration. Hepatology 2004 40:1322-1332.

Rudnick DA, Perlmutter DH and Muglia LJ. Prostaglandins are required for CREB Activation and Cellular Proliferation During Liver Regeneration. Proc. Natl. Acad Sci. USA 2001 98: 8885-8890.

Last Updated: 8/4/2011 11:56:40 AM

Back To Top

Follow us: