David A. Rudnick, M.D., Ph.D.  rudnick_d@wustl.edu

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Researcher, Developmental Biology
Gastroenterology, Hepatology and Nutrition

phone: (314) 454-6173

Research Interests

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.

  4. Clinical-translational studies of pediatric liver diseases – I am the WUSM PI for the national, multi-center Pediatric Acute Liver Failure Study Group (PALFSG). In addition to contributing patient data and biosamples to this study, we have led efforts to define metabolic biomarkers of outcome and the prevalences of specific rare genetically-based liver diseases in the PALFSG cohort.

Education

  • BS, University of Illinois1987
  • MD, Washington University School of Medicine1994
  • PhD, Washington University School of Medicine 1994

Training

  • Internship, St. Louis Children's Hospital1994 - 1995
  • Residency, St. Louis Children's Hospital1995 - 1997
  • Fellowship, Washington University School of Medicine1997 - 2000

Licensure and Board Certification

  • MO, 1997
  • American Board of Pediatrics, General Pediatrics 1997
  • American Board of Pediatrics, Sub-board of Pediatric Gastroenterology 2001
  • American Board of Pediatrics, General Pediatrics, Recertification 2004
  • American Board of Pediatrics, Sub-board of Pediatric Gastroenterology, Recertification 2008

Honors

  • Phi Beta Kappa, University of Illinois Chapter1987
  • Summa Cum Laude, University of Illinois1987
  • American Federation for Clinical Research, Medical Student Award, Washington University Medical School1992
  • Spencer T. and Ann W. Olin Foundation Medical Scientist Predoctoral, Fellowship, Washington University Medical School1992
  • American College of Physicians Award for Excellence in Physical Diagnosis, Washington University Medical School1993
  • Alpha Omega Alpha, Washington University Medical School Chapter1994
  • The Dr. Phillip Needleman Pharmacology Award, Washington University Medical School1994
  • The George F. Gill Prize in Pediatrics, Washington University Medical School1994
  • Scholar of the Child Health Research Center for Excellence in Developmental Biology at Washington University Medical School2000 - 2003
  • NASPGHAN Young Faculty Investigator Award2003
  • Research Excellence in GI and Liver (REGAL) Award2003
  • Best Doctors in America2007 - Pres
  • WUMS Distinguished Investigator Award2008
  • NASPGHAN Foundation Mid-Level Career Development Award2015

Selected Publications view all (42)


Publication Co-Authors

1.
Prevalence and Significance of Autoantibodies in Children With Acute Liver Failure. J Pediatr Gastroenterol Nutr. 2017;64(2):210-217. PMCID:PMC5250572  PMID:27496798 
2.
Outcomes of Children With and Without Hepatic Encephalopathy From the Pediatric Acute Liver Failure Study Group. J Pediatr Gastroenterol Nutr. 2016;63(3):357-64. PMCID:PMC4992416  PMID:27367788 
3.
Postponing the Hypoglycemic Response to Partial Hepatectomy Delays Mouse Liver Regeneration. Am J Pathol. 2016;186(3):587-99. doi:10.1016/j.ajpath.2015.10.027  PMID:26772417 
4.
Dietary aflatoxin-induced stunting in a novel rat model: evidence for toxin-induced liver injury and hepatic growth hormone resistance. Pediatr Res. 2015;78(2):120-127. doi:10.1038/pr.2015.84  PMCID:PMC4506701  PMID:25938735 
5.
Baseline Analysis of a Young α-1-Antitrypsin Deficiency Liver Disease Cohort Reveals Frequent Portal Hypertension. J Pediatr Gastroenterol Nutr. 2015;61(1):94-101. doi:10.1097/MPG.0000000000000753  PMID:25651489 
6.
Fibroblast growth factor 15 deficiency impairs liver regeneration in mice. Am J Physiol Gastrointest Liver Physiol. 2014;306(10):G893-902. doi:10.1152/ajpgi.00337.2013  PMCID:PMC4024724  PMID:24699334 
7.
Elucidating the metabolic regulation of liver regeneration. Am J Pathol. 2014;184(2):309-21. PMCID:PMC3906487  PMID:24139945 
8.
Identification of an epigenetic signature of early mouse liver regeneration that is disrupted by Zn-HDAC inhibition. Epigenetics. 2014;9(11):1521-31. doi:10.4161/15592294.2014.983371  PMID:25482284 
9.
Pregnancy in an NTBC-treated patient with hereditary tyrosinemia type I. J Pediatr Gastroenterol Nutr. 2013. doi:10.1097/MPG.0b013e3182a27463  PMID:23838819 
10.
Characterization of the regulation and function of zinc-dependent histone deacetylases during rodent liver regeneration. Hepatology. 2013;57(5):1742-51. doi:10.1002/hep.26206  PMID:23258575 
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