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

Associate Professor
Pediatrics
Gastroenterology & Nutrition
Developmental Biology

Developmental, Regenerative and Stem Cell Biology Program

  • 314-286-2832

  • 314-286-2839

  • 314-286-2892

  • 8208

  • 3105 McDonnell Pediatric Research Bldg

  • rudnick_d@kids.wustl.edu

  • http://peds.wustl.edu//research/labs/Rudnick_David_A/

  • liver; regeneration; alpha 1 antitrypsin deficiency; liver disease; aflatoxin; acute liver failure; cell cycle; mouse models; epigenetics; metabolism

  • Molecular mechanisms of liver injury and regeneration

Research Abstract:

My laboratory’s major focus has been to elucidate the hepatic regenerative mechanisms by which the liver recovers from injury. Our long-term goal is to translate such knowledge into improved therapies for human liver diseases. We use mouse models of surgical partial liver resection and human alpha-1-antitrypsin deficiency liver disease as well as other paradigms to ask these questions. Our results have provided unique insights into the relationships between host metabolism, liver injury, and regeneration in response to such injury. Ongoing areas of current investigation include:

1. Metabolic Influences on Liver Regeneration – Based on our studies showing that alterations in glucose metabolism generate essential hepatic regenerative signals, we collaborated with Dr. Paul Cliften and the WUSM Genome Technology Access Center to define metabolic influences on epigenetic regulation of liver regeneration. We are collaborating with Dr. Sayee Anakk (University of Illinois) to investigate the influence of metabolically regulated nuclear hormone receptors on experimental liver regeneration. Our studies have also led to translational efforts to identify regenerative biomarkers that predict outcomes in pediatric acute liver failure.

2. Metabolic Influences on alpha-1-antitrypsin deficiency (ATD) Liver Disease – We previously characterized the hepatic regenerative response to ATD liver disease using the PiZ mouse model of that disease. Those studies led to a novel conceptual model for the pathogenesis of hepatocellular carcinoma in the human disease. We recently reestablished our collaboration with Dr. Perlmutter’s group on a project combining our expertise in the metabolic basis of liver regeneration and his lab’s expertise in ATD liver disease pathobiology. This project leverages several unique mouse models that we have developed together. Those models were generated based on results of studies by our collaborators (Drs. Silverman and Pak) using a C. elegans model of ATD, which implicated insulin signaling as an important determinant of the liver’s response to ATD-induced damage. We are collaborating with Drs. Perlmutter, Silverman, Pak and Luke to elucidate the mechanistic basis of this interesting discovery. Our long-term goal is to translate these observations into therapies that prevent or reverse liver disease in human ATD.

3. Dietary Aflatoxin-Induced Stunting and Liver Injury – We reported a novel rat model of dietary aflatoxin-exposure induced growth impairment and hepatic injury. We are using this model to investigate strategies with which to mitigate aflatoxin-induced pathology.

Selected Publications:

Huang J, Schriefer AE, Cliften PF, Dietzen D, Kulkarni S, Sing S, Monga SPS, and Rudnick DA. (2016) Postponing the hypoglycemic response to partial hepatectomy delays mouse liver regeneration. American Journal of Pathology, 186(3): 587-599. PMID: 26772417.

Huang J, Schriefer AE, Yang W, Cliften PF, and Rudnick DA. (2014) Identification of an Epigenetic Signature of Early Mouse Liver Regeneration that is Disrupted by Zn-HDAC Inhibition. Epigenetics, 9(11): 1521-1531. PMID: 25482284.

Huang, J., Rudnick D.A.. (2014) Elucidating the metabolic regulation of liver regeneration. American Journal of Pathology, 184(2):309-321. PMID: 24139945

Huang J, Barr E, Rudnick DA. Characterization of the regulation and function of zinc-dependent histone deacetylases during mouse liver regeneration. (2013) Hepatology; 57(5): 1742-1751. PMCID: PMC3825707

Gazit V, Huang J, Weymann A, Rudnick DA. Analysis of the role of hepatic PPAR gamma expression during mouse liver regeneration. (2012) Hepatology; 56(4):1489-98. PMCID:PMC3465497.

Gazit V, Weymann A, Hartman E, Finck BN, Hruz PW, Tzekov A, Rudnick DA. Liver regeneration is impaired in lipodystrophic fatty liver dystrophy mice. (2010) Hepatology; 52(6):2109-17. PMCID:PMC2991544.

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. (2009) Hepatology 50(1):207-215. PMID: 19441104.

Rudnick DA, Shikapwashya O, Blomenkamp K, and Teckman JH. Indomethacin Increases Liver Injury in a Murine Model of Liver Injury from Alpha-1-Antritrypsin Deficiency. (2006) Hepatology 44(4): 976-982. PMID: 17006946

Rudnick DA and Perlmutter DH, Alpha-1-Antitrypsin Deficiency: A New Paradigm for Hepatocellular Carcinoma in Genetic Liver Disease. (2005) Hepatology, 42: 514-521. PMID: 16044402.

Shteyer E, Liao Y, Muglia LJ, Hruz P, Rudnick DA. Disruption of Hepatic Adipogenesis is Associated with Impaired Liver Regeneration. (2004) Hepatology 40:1322-1332. PMID: 15565660

Rudnick DA, Liao Y, An JK, Muglia LJ, Perlmutter DH, Teckman JH. Analyses of hepatocellular proliferation in a mouse model of alpha-1-antitrypsin deficiency. (2004) Hepatology; 39:1048-55. PMID 15057909

Last Updated: 6/11/2018 10:23:24 AM

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