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

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

phone:

Education

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

Training

  • 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

  • PA, State of Pennsylvania Medical License 1978
  • MA, State of Massachusetts Medical License 1982
  • Pediatrics 1986
  • State of Missouri Medical License 1986
  • Pediatric Gastroenterology and Nutrition 1990

Honors

  • 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 
Last updated: 08/15/2017
© 2018 by Washington University in St. Louis
One Brookings Drive, St. Louis, MO 63130