David Perlmutter, M.D.  perlmutterd@wustl.edu

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Dean, School of Medicine
Executive Vice Chancellor of Medical Affairs
Professor of Pediatrics, Gastroenterology, Hepatology and Nutrition
Researcher, Developmental Biology
School of Medicine



  • BA, University of Rochester1974
  • MD, St. Louis University School of Medicine1978


  • Pediatric Intern, Children's Hospital of Philadelphia1978 - 1979
  • Junior Resident, Children's Hospital of Philadelphia1979 - 1980
  • Assistant Chief Resident, Children's Hospital of Philadelphia1980 - 1981
  • Clinical Fellow, Boston Children's Hospital1981 - 1982
  • Research Fellow, Boston Children's Hospital1982 - 1984

Licensure and Board Certification

  • 1978PA, State of Pennsylvania Medical License
  • 1982MA, State of Massachusetts Medical License
  • 1986 - PresPediatrics
  • 1986State of Missouri Medical License
  • 1990 - PresPediatric Gastroenterology and Nutrition

Honors and Awards

  • Alpha Omega Alpha1978
  • Alpha Sigma Nu, National Jesuit Honor Society, St. Louis University1978
  • Arthur E. McElfresh Department of Pediatrics Award, St. Louis University School of Medicine1978
  • Department of Neurology Award, St. Louis University School of Medicine1978
  • American Liver Foundation Postdoctoral Award1983
  • Charles A Hood Foundation Postdoctoral Award1984
  • American Gastroenterological Association/Industry Research Scholar Award1985
  • Charles A. Janeway Fellowship Award1985
  • RJR Nabisco Research Scholars Award1986
  • Society for Pediatric Research Young Investigator Award (Honorable Mention)1986
  • American Heart Association Established Investigator Award1987
  • Burroughs Wellcome Scholar in Experimental Therapeutics Award1993
  • E. Mead Johnson Award for Research in Pediatrics1994
  • Donald Strominger Endowed Chair/Professorship, Washington University1996
  • Vira I. Heinz Endowed Chair, Children’s Hospital of Pittsburgh/University of Pittsburgh2001
  • Sass-Kortsak Award for Pediatric Liver Research, Canadian Liver Association2006
  • Shwachman Award for Lifetime Achievement, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition2011
  • David H Perlmutter Research Endowment, University of Pittsburgh Medical Center/Children’s Hospital of Pittsburgh Foundation2013
  • American Association for the Study of Liver Disease, AASLD Fellow2014

Recent Publications view all (97)

Publication Co-Authors

  1. Current and Emerging Treatments for Alpha-1 Antitrypsin Deficiency. Gastroenterol Hepatol (N Y). 2016;12(7):446-8. PMCID:PMC4969782  PMID:27489528 
  2. Is severe progressive liver disease caused by alpha-1-antitrypsin deficiency more common in children or adults? Liver Transpl. 2016;22(7):886-94. PMID:26946192 
  3. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 2016;12(1):1-222. PMCID:PMC4835977  PMID:26799652 
  4. Enhancing Autophagy with Drugs or Lung-directed Gene Therapy Reverses the Pathological Effects of Respiratory Epithelial Cell Proteinopathy. J Biol Chem. 2015;290(50):29742-57. PMCID:PMC4705969  PMID:26494620 
  5. Induced pluripotent stem cells model personalized variations in liver disease resulting from α1-antitrypsin deficiency. Hepatology. 2015;62(1):147-57. PMCID:PMC4482790  PMID:25690322 
  6. Two New Considerations for Improving the Diagnosis of α1-Antitrypsin Deficiency-Associated Liver Disease. Dig Dis Sci. 2015;60(6):1511-3. PMCID:PMC4456220  PMID:25634676 
  7. The aggregation-prone intracellular serpin SRP-2 fails to transit the ER in Caenorhabditis elegans. Genetics. 2015;200(1):207-19. PMCID:PMC4423363  PMID:25786854 
  8. Deficient and Null Variants of SERPINA1 Are Proteotoxic in a Caenorhabditis elegans Model of α1-Antitrypsin Deficiency. PLoS One. 2015;10(10):e0141542. PMCID:PMC4626213  PMID:26512890 
  9. A genome-wide RNAi screen identifies potential drug targets in a C. elegans model of α1-antitrypsin deficiency. Hum Mol Genet. 2014;23(19):5123-32. PMCID:PMC4159156  PMID:24838285 
  10. A C. elegans model of human α1-antitrypsin deficiency links components of the RNAi pathway to misfolded protein turnover. Hum Mol Genet. 2014;23(19):5109-22. PMCID:PMC4159155  PMID:24838286 
  11. Worming our way to novel drug discovery with the Caenorhabditis elegans proteostasis network, stress response and insulin-signaling pathways. Expert Opin Drug Discov. 2014;9(9):1021-32. PMID:24998976 
  12. C. elegans in high-throughput drug discovery. Adv Drug Deliv Rev. 2014;69-70:247-53. PMCID:PMC4019719  PMID:24333896 
  13. Mysteries of α1-antitrypsin deficiency: emerging therapeutic strategies for a challenging disease. Dis Model Mech. 2014;7(4):411-9. PMCID:PMC3974452  PMID:24719116 
  14. α1-antitrypsin deficiency and the hepatocytes - an elegans solution to drug discovery. Int J Biochem Cell Biol. 2014;47:109-12. PMCID:PMC3970812  PMID:24355812 
  15. Capitalizing on the autophagic response for treatment of liver disease caused by alpha-1-antitrypsin deficiency and other genetic diseases. Biomed Res Int. 2014;2014:459823. PMCID:PMC4065733  PMID:25025052 
  16. Fluphenazine reduces proteotoxicity in C. elegans and mammalian models of alpha-1-antitrypsin deficiency. PLoS One. 2014;9(1):e87260. PMCID:PMC3909079  PMID:24498058 
  17. Targeting intracellular degradation pathways for treatment of liver disease caused by α1-antitrypsin deficiency. Pediatr Res. 2014;75(1-2):133-9. PMCID:PMC4174576  PMID:24226634 
  18. Disorders of protein misfolding: alpha-1-antitrypsin deficiency as prototype. J Pediatr. 2013;163(2):320-6. PMCID:PMC3725216  PMID:23664631 
  19. Functions of autophagy in normal and diseased liver. Autophagy. 2013;9(8):1131-58. PMCID:PMC3748187  PMID:23774882 
  20. The endosomal protein-sorting receptor sortilin has a role in trafficking α-1 antitrypsin. Genetics. 2012;192(3):889-903. PMCID:PMC3522165  PMID:22923381 
  21. Clathrin pit-mediated endocytosis of neutrophil elastase and cathepsin G by cancer cells. J Biol Chem. 2012;287(42):35341-50. PMCID:PMC3471748  PMID:22915586 
  22. Novel treatment strategies for liver disease due to α1-antitrypsin deficiency. Clin Transl Sci. 2012;5(3):289-94. PMCID:PMC3982223  PMID:22686209 
  23. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy. 2012;8(4):445-544. PMCID:PMC3404883  PMID:22966490 
  24. A pro-cathepsin L mutant is a luminal substrate for endoplasmic-reticulum-associated degradation in C. elegans. PLoS One. 2012;7(7):e40145. PMCID:PMC3388072  PMID:22768338 
  25. Spontaneous hepatic repopulation in transgenic mice expressing mutant human α1-antitrypsin by wild-type donor hepatocytes. J Clin Invest. 2011;121(5):1930-4. PMCID:PMC3083768  PMID:21505264 
  26. Hepatic fibrosis and carcinogenesis in α1-antitrypsin deficiency: a prototype for chronic tissue damage in gain-of-function disorders. Cold Spring Harb Perspect Biol. 2011;3(3). PMCID:PMC3039936  PMID:21421920 
  27. Alpha-1-antitrypsin deficiency: importance of proteasomal and autophagic degradative pathways in disposal of liver disease-associated protein aggregates. Annu Rev Med. 2011;62:333-45. PMID:20707674 
  28. Using Caenorhabditis elegans to study serpinopathies. Methods Enzymol. 2011;499:259-81. PMCID:PMC4374434  PMID:21683258 
  29. The role of autophagy in alpha-1-antitrypsin deficiency. Methods Enzymol. 2011;499:33-54. PMID:21683248 
  30. Automated high-content live animal drug screening using C. elegans expressing the aggregation prone serpin α1-antitrypsin Z. PLoS One. 2010;5(11):e15460. PMCID:PMC2980495  PMID:21103396 
  31. An autophagy-enhancing drug promotes degradation of mutant alpha1-antitrypsin Z and reduces hepatic fibrosis. Science. 2010;329(5988):229-32. PMID:20522742 
  32. Autophagic disposal of the aggregation-prone protein that causes liver inflammation and carcinogenesis in alpha-1-antitrypsin deficiency. Cell Death Differ. 2009;16(1):39-45. PMID:18617899 
  33. Modeling molecular and cellular aspects of human disease using the nematode Caenorhabditis elegans. Pediatr Res. 2009;65(1):10-8. PMCID:PMC2731241  PMID:18852689 
  34. Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy. 2008;4(2):151-75. PMCID:PMC2654259  PMID:18188003 
  35. ADD66, a gene involved in the endoplasmic reticulum-associated degradation of alpha-1-antitrypsin-Z in yeast, facilitates proteasome activity and assembly. Mol Biol Cell. 2007;18(10):3776-87. PMCID:PMC1995736  PMID:17634286 
  36. Regulator of G Signaling 16 is a marker for the distinct endoplasmic reticulum stress state associated with aggregated mutant alpha1-antitrypsin Z in the classical form of alpha1-antitrypsin deficiency. J Biol Chem. 2007;282(38):27769-80. PMID:17635928 
  37. Molecular pathogenesis of alpha-1-antitrypsin deficiency-associated liver disease: a meeting review. Hepatology. 2007;45(5):1313-23. PMID:17464974 
  38. The role of autophagy in alpha-1-antitrypsin deficiency: a specific cellular response in genetic diseases associated with aggregation-prone proteins. Autophagy. 2006;2(4):258-63. PMID:16874089 
  39. Pathogenesis of chronic liver injury and hepatocellular carcinoma in alpha-1-antitrypsin deficiency. Pediatr Res. 2006;60(2):233-8. PMID:16864711 
  40. Intracellular inclusions containing mutant alpha1-antitrypsin Z are propagated in the absence of autophagic activity. J Biol Chem. 2006;281(7):4467-76. PMID:16365039 
  41. Accumulation of mutant alpha1-antitrypsin Z in the endoplasmic reticulum activates caspases-4 and -12, NFkappaB, and BAP31 but not the unfolded protein response. J Biol Chem. 2005;280(47):39002-15. PMID:16183649 
  42. Grp78, Grp94, and Grp170 interact with alpha1-antitrypsin mutants that are retained in the endoplasmic reticulum. Am J Physiol Gastrointest Liver Physiol. 2005;289(3):G444-55. PMID:15845869 
  43. Alpha-1-antitrypsin deficiency: a new paradigm for hepatocellular carcinoma in genetic liver disease. Hepatology. 2005;42(3):514-21. PMID:16044402 
  44. Alpha-1-antitrypsin deficiency: diagnosis and treatment. Clin Liver Dis. 2004;8(4):839-59, viii-ix. PMID:15464658 
  45. Analyses of hepatocellular proliferation in a mouse model of alpha-1-antitrypsin deficiency. Hepatology. 2004;39(4):1048-55. PMID:15057909 
  46. Alpha1-antitrypsin deficiency: liver disease associated with retention of a mutant secretory glycoprotein in the endoplasmic reticulum. Methods Mol Biol. 2003;232:39-56. PMID:12840538 
  47. Liver injury in alpha1-antitrypsin deficiency: an aggregated protein induces mitochondrial injury. J Clin Invest. 2002;110(11):1579-83. PMCID:PMC151639  PMID:12464659 
  48. Chemical chaperones: a pharmacological strategy for disorders of protein folding and trafficking. Pediatr Res. 2002;52(6):832-6. PMID:12438657 
  49. The cellular response to aggregated proteins associated with human disease. J Clin Invest. 2002;110(9):1219-20. PMCID:PMC151619  PMID:12417557 
  50. Fasting in alpha1-antitrypsin deficient liver: constitutive [correction of consultative] activation of autophagy. Am J Physiol Gastrointest Liver Physiol. 2002;283(5):G1156-65. PMID:12381530 
  51. Extrahepatic biliary atresia: a disease or a phenotype? Hepatology. 2002;35(6):1297-304. PMID:12029613 
  52. Cell-specific involvement of HNF-1beta in alpha(1)-antitrypsin gene expression in human respiratory epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2002;282(4):L757-65. PMID:11880302 
  53. Research agenda for pediatric gastroenterology, hepatology and nutrition: molecular basis of gastrointestinal diseases. Report of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition for the Children's Digestive Health and Nutrition Foundation. J Pediatr Gastroenterol Nutr. 2002;35 Suppl 3:S237-41. PMID:12394357 
  54. Metabolic liver disease. J Pediatr Gastroenterol Nutr. 2002;35 Suppl 1:S24-8. PMID:12151817 
  55. The proteasome participates in degradation of mutant alpha 1-antitrypsin Z in the endoplasmic reticulum of hepatoma-derived hepatocytes. J Biol Chem. 2001;276(48):44865-72. PMID:11577074 
  56. A naturally occurring nonpolymerogenic mutant of alpha 1-antitrypsin characterized by prolonged retention in the endoplasmic reticulum. J Biol Chem. 2001;276(36):33893-8. PMID:11427540 
  57. Prostaglandins are required for CREB activation and cellular proliferation during liver regeneration. Proc Natl Acad Sci U S A. 2001;98(15):8885-90. PMCID:PMC37530  PMID:11447268 
  58. Outcome of early hepatic portoenterostomy for biliary atresia. J Pediatr Gastroenterol Nutr. 2001;32(3):265-9. PMID:11345173 
  59. Alpha(1)-Antitrypsin Deficiency. Curr Treat Options Gastroenterol. 2000;3(6):451-456. PMID:11096605 
  60. Retention of mutant alpha(1)-antitrypsin Z in endoplasmic reticulum is associated with an autophagic response. Am J Physiol Gastrointest Liver Physiol. 2000;279(5):G961-74. PMID:11052993 
  61. Alpha1-antitrypsin deficiency-associated liver disease progresses slowly in some children. J Pediatr Gastroenterol Nutr. 2000;31(3):258-63. PMID:10997369 
  62. Circulating serpin tumor markers SCCA1 and SCCA2 are not actively secreted but reside in the cytosol of squamous carcinoma cells. Int J Cancer. 2000;89(4):368-77. PMID:10956412 
  63. Liver injury in alpha 1-antitrypsin deficiency. Clin Liver Dis. 2000;4(2):387-408, vi. PMID:11232197 
  64. Chemical chaperones mediate increased secretion of mutant alpha 1-antitrypsin (alpha 1-AT) Z: A potential pharmacological strategy for prevention of liver injury and emphysema in alpha 1-AT deficiency. Proc Natl Acad Sci U S A. 2000;97(4):1796-801. PMCID:PMC26515  PMID:10677536 
  65. Glucosidase and mannosidase inhibitors mediate increased secretion of mutant alpha1 antitrypsin Z. J Biol Chem. 2000;275(3):1987-92. PMID:10636901 
  66. Role of ubiquitin in proteasomal degradation of mutant alpha(1)-antitrypsin Z in the endoplasmic reticulum. Am J Physiol Gastrointest Liver Physiol. 2000;278(1):G39-48. PMID:10644560 
  67. Primary gastric plasmacytoma: a rare cause of hypertrophic gastritis in an adolescent. J Pediatr Gastroenterol Nutr. 1999;29(4):424-30. PMID:10512402 
  68. Anomalous development of the hepatobiliary system in the Inv mouse. Hepatology. 1999;30(2):372-8. PMID:10421642 
  69. Misfolded proteins in the endoplasmic reticulum. Lab Invest. 1999;79(6):623-38. PMID:10378505 
  70. Regulation of alpha1-antitrypsin gene expression in human intestinal epithelial cell line caco-2 by HNF-1alpha and HNF-4. Am J Physiol. 1999;276(5 Pt 1):G1181-94. PMID:10330009 
  71. Disruption of disulfide bonds is responsible for impaired secretion in human complement factor H deficiency. J Biol Chem. 1999;274(17):11782-8. PMID:10206995 
  72. Chain length of the polylysine in receptor-targeted gene transfer complexes affects duration of reporter gene expression both in vitro and in vivo. J Biol Chem. 1999;274(8):4908-16. PMID:9988733 
  73. Ligand substitution of receptor targeted DNA complexes affects gene transfer into hepatoma cells. Gene Ther. 1998;5(12):1685-97. PMID:10023448 
  74. Alpha1-antitrypsin deficiency: from genotype to childhood disease. J Pediatr Gastroenterol Nutr. 1998;27(1):65-74. PMID:9669729 
  75. Resistance to the apoptotic effect of aggregated amyloid-beta peptide in several different cell types including neuronal- and hepatoma-derived cell lines. Biochem J. 1998;332 ( Pt 2):517-24. PMCID:PMC1219508  PMID:9601082 
  76. Alpha-1-antitrypsin deficiency. Semin Liver Dis. 1998;18(3):217-25. PMID:9773422 
  77. Gene transfer into hepatoma cell lines via the serpin enzyme complex receptor. Am J Physiol. 1997;273(2 Pt 1):G545-52. PMCID:PMC4064792  PMID:9277436 
  78. Reconstitution of bile acid transport in a heterologous cell by cotransfection of transporters for bile acid uptake and efflux. J Biol Chem. 1997;272(29):18290-7. PMID:9218468 
  79. Review: alpha 1-antitrypsin deficiency associated liver disease. J Gastroenterol Hepatol. 1997;12(5):404-16. PMID:9195389 
  80. Site-directed mutagenesis within an ectoplasmic ATPase consensus sequence abrogates the cell aggregating properties of the rat liver canalicular bile acid transporter/ecto-ATPase/cell CAM 105 and carcinoembryonic antigen. J Biol Chem. 1996;271(51):33095-104. PMID:8955157 
  81. Molecular pathogenesis of liver disease in alpha1-antitrypsin deficiency. Hepatology. 1996;24(6):1504-16. PMID:8938188 
  82. Alpha-1-antitrypsin deficiency: biochemistry and clinical manifestations. Ann Med. 1996;28(5):385-94. PMID:8949968 
  83. Degradation of a mutant secretory protein, alpha1-antitrypsin Z, in the endoplasmic reticulum requires proteasome activity. J Biol Chem. 1996;271(37):22791-5. PMID:8798455 
  84. The serpin-enzyme complex receptor recognizes soluble, nontoxic amyloid-beta peptide but not aggregated, cytotoxic amyloid-beta peptide. J Biol Chem. 1996;271(30):18032-44. PMID:8663372 
  85. Biliary atresia: current concepts and research directions. Summary of a symposium. Hepatology. 1996;23(6):1682-92. PMID:8675193 
  86. The endoplasmic reticulum degradation pathway for mutant secretory proteins alpha1-antitrypsin Z and S is distinct from that for an unassembled membrane protein. J Biol Chem. 1996;271(22):13215-20. PMID:8662752 
  87. Regulation of sucrase-isomaltase gene expression in human intestinal epithelial cells by inflammatory cytokines. J Biol Chem. 1996;271(2):1237-42. PMID:8557656 
  88. Society for Pediatric Research presidential address 1995: marrying our medicine to biology. Pediatr Res. 1995;38(6):830-4. PMID:8618781 
  89. Specificity in recognition of amyloid-beta peptide by the serpin-enzyme complex receptor in hepatoma cells and neuronal cells. J Biol Chem. 1995;270(47):28022-8. PMID:7499286 
  90. N-formylpeptide and complement C5a receptors are expressed in liver cells and mediate hepatic acute phase gene regulation. J Exp Med. 1995;182(1):207-17. PMCID:PMC2192098  PMID:7540650 
  91. Conceptual advances in the pathogenesis and treatment of childhood metabolic liver disease. Gastroenterology. 1995;108(4):1263-79. PMID:7698594 
  92. Clinical manifestations of alpha 1-antitrypsin deficiency. Gastroenterol Clin North Am. 1995;24(1):27-43. PMID:7729860 
  93. Cellular expression of the C5a anaphylatoxin receptor (C5aR): demonstration of C5aR on nonmyeloid cells of the liver and lung. J Immunol. 1995;154(4):1861-9. PMID:7836770 
  94. A lag in intracellular degradation of mutant alpha 1-antitrypsin correlates with the liver disease phenotype in homozygous PiZZ alpha 1-antitrypsin deficiency. Proc Natl Acad Sci U S A. 1994;91(19):9014-8. PMCID:PMC44737  PMID:8090762 
  95. The SEC receptor: a possible link between neonatal hepatitis in alpha 1-antitrypsin deficiency and Alzheimer's disease. Pediatr Res. 1994;36(3):271-7. PMID:7808820 
  96. Bile acid efflux mediated by the rat liver canalicular bile acid transport/ecto-ATPase protein requires serine 503 phosphorylation and is regulated by tyrosine 488 phosphorylation. J Biol Chem. 1994;269(30):19539-45. PMID:7518458 
  97. Metabolic liver disease in childhood. Semin Gastrointest Dis. 1994;5(2):54-64. PMID:8049907 
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