David Perlmutter

Summary

Affiliation: Children's Hospital of Pittsburgh
Country: USA

Publications

  1. doi request reprint An autophagy-enhancing drug promotes degradation of mutant alpha1-antitrypsin Z and reduces hepatic fibrosis
    Tunda Hidvegi
    Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    Science 329:229-32. 2010
  2. pmc Mysteries of α1-antitrypsin deficiency: emerging therapeutic strategies for a challenging disease
    Raafe Ghouse
    Department of Pediatrics, University of Pittsburgh School of Medicine, One Children s Hospital Drive, 4401 Penn Avenue, Pittsburgh, PA 15224, USA
    Dis Model Mech 7:411-9. 2014
  3. pmc Fluphenazine reduces proteotoxicity in C. elegans and mammalian models of alpha-1-antitrypsin deficiency
    Jie Li
    Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America Children s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States of America
    PLoS ONE 9:e87260. 2014
  4. ncbi request reprint Alpha-1-antitrypsin deficiency: diagnosis and treatment
    David H Perlmutter
    University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
    Clin Liver Dis 8:839-59, viii-ix. 2004
  5. ncbi request reprint Pathogenesis of chronic liver injury and hepatocellular carcinoma in alpha-1-antitrypsin deficiency
    David H Perlmutter
    Department of Pediatrics, University of Pittsburgh School of Medicine, Children s Hospital of Pittsburgh, PA 15213, USA
    Pediatr Res 60:233-8. 2006
  6. ncbi request reprint The role of autophagy in alpha-1-antitrypsin deficiency: a specific cellular response in genetic diseases associated with aggregation-prone proteins
    David H Perlmutter
    Department of Pediatrics and Cell Biology, University of Pittsburgh School of Medicine, Childrens Hospital of Pittsburgh, Pynnsylvania 15213, USA
    Autophagy 2:258-63. 2006
  7. pmc Liver injury in alpha1-antitrypsin deficiency: an aggregated protein induces mitochondrial injury
    David H Perlmutter
    University of Pittsburgh School of Medicine, Children s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
    J Clin Invest 110:1579-83. 2002
  8. ncbi request reprint Molecular pathogenesis of alpha-1-antitrypsin deficiency-associated liver disease: a meeting review
    David H Perlmutter
    Department of Pediatrics, University of Pittsburgh School of Medicine, Children s Hospital of Pittsburgh, Pittsburgh, PA 15213, USA
    Hepatology 45:1313-23. 2007
  9. doi request reprint Autophagic disposal of the aggregation-prone protein that causes liver inflammation and carcinogenesis in alpha-1-antitrypsin deficiency
    D H Perlmutter
    Department of Pediatrics, Cell Biology and Physiology, University of Pittsburgh School of Medicine, Children s Hospital of Pittsburgh of UPMC, 3705 Fifth Avenue, Pittsburgh, PA 15213 2583, USA
    Cell Death Differ 16:39-45. 2009
  10. doi request reprint Alpha-1-antitrypsin deficiency: importance of proteasomal and autophagic degradative pathways in disposal of liver disease-associated protein aggregates
    David H Perlmutter
    Department of Pediatrics, Cell Biology and Physiology, University of Pittsburgh School of Medicine, Children s Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania 15217, USA
    Annu Rev Med 62:333-45. 2011

Research Grants

  1. Novel Pharmacological Strategies for Liver Disease in Antitrypsin Deficiency
    David H Perlmutter; Fiscal Year: 2010
  2. LOCAL EXPRESSION OF ALPHA-1-ANTITRYPSIN IN EMPHYSEMA
    David Perlmutter; Fiscal Year: 1990
  3. LIVER INJURY IN ALPHA 1 ANTITRYPSIN DEFICIENCY
    David Perlmutter; Fiscal Year: 2001
  4. Liver Injury in Alpha-1-Antitrypsin Deficiency
    David Perlmutter; Fiscal Year: 2001
  5. Liver Injury in Alpha-1-Antitrypsin Deficiency
    David Perlmutter; Fiscal Year: 2006
  6. LOCAL EXPRESSION OF ALPHA-1-ANTITRYPSIN IN EMPHYSEMA
    David Perlmutter; Fiscal Year: 2005
  7. LOCAL EXPRESSION OF ALPHA-1-ANTITRYPSIN IN EMPHYSEMA
    David Perlmutter; Fiscal Year: 2003
  8. LOCAL EXPRESSION OF ALPHA-1-ANTITRYPSIN IN EMPHYSEMA
    David Perlmutter; Fiscal Year: 1993
  9. LIVER INJURY IN ALPHA 1 ANTITRYPSIN DEFICIENCY
    David Perlmutter; Fiscal Year: 1999
  10. Hepatocellular Carcinoma in Antitrypsin Deficiency
    David H Perlmutter; Fiscal Year: 2010

Collaborators

Detail Information

Publications26

  1. doi request reprint An autophagy-enhancing drug promotes degradation of mutant alpha1-antitrypsin Z and reduces hepatic fibrosis
    Tunda Hidvegi
    Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA
    Science 329:229-32. 2010
    ..These results provide a basis for testing CBZ, which has an extensive clinical safety profile, in patients with AT deficiency and also provide a proof of principle for therapeutic use of autophagy enhancers...
  2. pmc Mysteries of α1-antitrypsin deficiency: emerging therapeutic strategies for a challenging disease
    Raafe Ghouse
    Department of Pediatrics, University of Pittsburgh School of Medicine, One Children s Hospital Drive, 4401 Penn Avenue, Pittsburgh, PA 15224, USA
    Dis Model Mech 7:411-9. 2014
    ..Nevertheless, advances in understanding the variability in clinical phenotype and in developing novel therapeutic concepts is beginning to address the major clinical challenges of this mysterious disorder. ..
  3. pmc Fluphenazine reduces proteotoxicity in C. elegans and mammalian models of alpha-1-antitrypsin deficiency
    Jie Li
    Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America Children s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States of America
    PLoS ONE 9:e87260. 2014
    ..The results also provide further validation for drug discovery using C. elegans models that can be adapted to high-content drug screening platforms and used together with mammalian cell line and animal models. ..
  4. ncbi request reprint Alpha-1-antitrypsin deficiency: diagnosis and treatment
    David H Perlmutter
    University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
    Clin Liver Dis 8:839-59, viii-ix. 2004
    ..Observations indicate that genetic traits unlinked to the AT gene or environmental factors predispose to or protect AT-deficient individuals from liver disease...
  5. ncbi request reprint Pathogenesis of chronic liver injury and hepatocellular carcinoma in alpha-1-antitrypsin deficiency
    David H Perlmutter
    Department of Pediatrics, University of Pittsburgh School of Medicine, Children s Hospital of Pittsburgh, PA 15213, USA
    Pediatr Res 60:233-8. 2006
    ..Aspects of this hypothetical paradigm may also explain the proclivity for hepatocarcinogenesis in other chronic liver diseases, including other genetic diseases, viral hepatitis, and nonalcoholic steatohepatitis...
  6. ncbi request reprint The role of autophagy in alpha-1-antitrypsin deficiency: a specific cellular response in genetic diseases associated with aggregation-prone proteins
    David H Perlmutter
    Department of Pediatrics and Cell Biology, University of Pittsburgh School of Medicine, Childrens Hospital of Pittsburgh, Pynnsylvania 15213, USA
    Autophagy 2:258-63. 2006
    ..Together, these studies provide further evidence for the importance of autophagy in the cellular adaptive response to aggregated proteins in general...
  7. pmc Liver injury in alpha1-antitrypsin deficiency: an aggregated protein induces mitochondrial injury
    David H Perlmutter
    University of Pittsburgh School of Medicine, Children s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
    J Clin Invest 110:1579-83. 2002
  8. ncbi request reprint Molecular pathogenesis of alpha-1-antitrypsin deficiency-associated liver disease: a meeting review
    David H Perlmutter
    Department of Pediatrics, University of Pittsburgh School of Medicine, Children s Hospital of Pittsburgh, Pittsburgh, PA 15213, USA
    Hepatology 45:1313-23. 2007
    ..A session of the meeting was devoted to novel therapeutic strategies being developed for AT deficiency as well as to strategies either in development or already being applied to the class of diseases associated with mutant proteins...
  9. doi request reprint Autophagic disposal of the aggregation-prone protein that causes liver inflammation and carcinogenesis in alpha-1-antitrypsin deficiency
    D H Perlmutter
    Department of Pediatrics, Cell Biology and Physiology, University of Pittsburgh School of Medicine, Children s Hospital of Pittsburgh of UPMC, 3705 Fifth Avenue, Pittsburgh, PA 15213 2583, USA
    Cell Death Differ 16:39-45. 2009
    ....
  10. doi request reprint Alpha-1-antitrypsin deficiency: importance of proteasomal and autophagic degradative pathways in disposal of liver disease-associated protein aggregates
    David H Perlmutter
    Department of Pediatrics, Cell Biology and Physiology, University of Pittsburgh School of Medicine, Children s Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania 15217, USA
    Annu Rev Med 62:333-45. 2011
    ..Exciting recent results have shown that a drug that enhances autophagy can reduce the hepatic load of aggregated protein and reverse fibrosis in a mouse model of this disease...
  11. ncbi request reprint 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
    Tunda Hidvegi
    Department of Pediatrics, University of Pittsburgh School of Medicine, Children s Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    J Biol Chem 282:27769-80. 2007
    ....
  12. ncbi request reprint Accumulation of mutant alpha1-antitrypsin Z in the endoplasmic reticulum activates caspases-4 and -12, NFkappaB, and BAP31 but not the unfolded protein response
    Tunda Hidvegi
    Department of Pediatrics, University of Pittsburgh School of Medicine, Children s Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA
    J Biol Chem 280:39002-15. 2005
    ..Accumulation of mutant alpha1ATZ does activate specific signaling pathways, including caspase-12 in mouse, caspase-4 in human, NFkappaB, and BAP31, a profile that was distinct from that activated by nonpolymerogenic alpha1AT mutants...
  13. pmc The cellular response to aggregated proteins associated with human disease
    David H Perlmutter
    University of Pittsburgh School of Medicine and Children s Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213 2583, USA
    J Clin Invest 110:1219-20. 2002
  14. ncbi request reprint Grp78, Grp94, and Grp170 interact with alpha1-antitrypsin mutants that are retained in the endoplasmic reticulum
    Bela Z Schmidt
    Department of Pediatrics, Univ of Pittsburgh School of Medicine, Children s Hospital of Pittsburgh, 3705 Fifth Ave, Pittsburgh, PA 15213 2583, USA
    Am J Physiol Gastrointest Liver Physiol 289:G444-55. 2005
    ..Agents that perturb the synthesis and/or activity of ER chaperones such as tunicamycin and calcium ionophore A23187, have different effects on the solubility and degradation of alpha1-AT Z as well as on its residual secretion...
  15. ncbi request reprint Extrahepatic biliary atresia: a disease or a phenotype?
    David H Perlmutter
    Department of Pediatrics, Washington University School of Medicine, USA
    Hepatology 35:1297-304. 2002
  16. ncbi request reprint Analyses of hepatocellular proliferation in a mouse model of alpha-1-antitrypsin deficiency
    David A Rudnick
    Department of Pediatrics, Washington University School of Medicine, St Louis, MO 63110, USA
    Hepatology 39:1048-55. 2004
    ..This selective proliferation suggests that hepatocellular transplantation may be applicable for treatment of this and other slowly progressive metabolic liver diseases...
  17. ncbi request reprint Alpha1-antitrypsin deficiency: liver disease associated with retention of a mutant secretory glycoprotein in the endoplasmic reticulum
    David H Perlmutter
    Department of Pediatrics, University of Pittsburgh School of Medicine, PA, USA
    Methods Mol Biol 232:39-56. 2003
  18. ncbi request reprint Chemical chaperones: a pharmacological strategy for disorders of protein folding and trafficking
    David H Perlmutter
    Department of Pediatrics, University of Pittsburgh School of Medicine, Children s Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213 2583, USA
    Pediatr Res 52:832-6. 2002
  19. ncbi request reprint Fasting in alpha1-antitrypsin deficient liver: constitutive [correction of consultative] activation of autophagy
    Jeffrey H Teckman
    Department of Pediatrics, St Louis Children s Hospital, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Am J Physiol Gastrointest Liver Physiol 283:G1156-65. 2002
    ....
  20. ncbi request reprint Cell-specific involvement of HNF-1beta in alpha(1)-antitrypsin gene expression in human respiratory epithelial cells
    Chaobin Hu
    Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Am J Physiol Lung Cell Mol Physiol 282:L757-65. 2002
    ..These results indicate the unique involvement of HNF-1beta in alpha(1)-AT gene expression in a cell line and primary cultures derived from human respiratory epithelium...
  21. pmc ADD66, a gene involved in the endoplasmic reticulum-associated degradation of alpha-1-antitrypsin-Z in yeast, facilitates proteasome activity and assembly
    Craig M Scott
    Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA
    Mol Biol Cell 18:3776-87. 2007
    ..These data identify Add66p as a proteasome assembly chaperone (PAC), and they provide the first link between PAC activity and ERAD...
  22. ncbi request reprint Metabolic liver disease
    David H Perlmutter
    Children s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA
    J Pediatr Gastroenterol Nutr 35:S24-8. 2002
  23. pmc Modeling molecular and cellular aspects of human disease using the nematode Caenorhabditis elegans
    Gary A Silverman
    Department of Pediatrics, Children s Hospital of Pittsburgh and Magee Womens Hospital Research Institute, Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA
    Pediatr Res 65:10-8. 2009
    ..elegans, manifesting different aspects of human disease phenotypes, will become the platform of choice for in vivo drug discovery and target validation using high-throughput/content screening technologies...
  24. ncbi request reprint Alpha-1-antitrypsin deficiency: a new paradigm for hepatocellular carcinoma in genetic liver disease
    David A Rudnick
    Department of Pediatics, Washington University School of Medicine, St Louis, MO, USA
    Hepatology 42:514-21. 2005
    ..Further, this paradigm may apply to other genetic and infectious liver diseases that are predisposed to hepatocellular carcinoma...
  25. ncbi request reprint 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 N
    David H Perlmutter
    Children s Digestive Health and Nutrition Foundation, PO Box 6, Flourtown, PA 19031, USA
    J Pediatr Gastroenterol Nutr 35:S237-41. 2002
  26. ncbi request reprint Intracellular inclusions containing mutant alpha1-antitrypsin Z are propagated in the absence of autophagic activity
    Takahiro Kamimoto
    Department of Cell Genetics, National Institute of Genetics, Mishima, Japan
    J Biol Chem 281:4467-76. 2006
    ....

Research Grants48

  1. Novel Pharmacological Strategies for Liver Disease in Antitrypsin Deficiency
    David H Perlmutter; Fiscal Year: 2010
    ....
  2. LOCAL EXPRESSION OF ALPHA-1-ANTITRYPSIN IN EMPHYSEMA
    David Perlmutter; Fiscal Year: 1990
    ..These studies have broad application to the understanding of this common genetic deficiency, consequent injury to lung and liver and to the development of new therapeutic strategies...
  3. LIVER INJURY IN ALPHA 1 ANTITRYPSIN DEFICIENCY
    David Perlmutter; Fiscal Year: 2001
    ....
  4. Liver Injury in Alpha-1-Antitrypsin Deficiency
    David Perlmutter; Fiscal Year: 2001
    ....
  5. Liver Injury in Alpha-1-Antitrypsin Deficiency
    David Perlmutter; Fiscal Year: 2006
    ..Thus, the studies proposed in this competitive renewal application will address the novel concept that oxidative stress causes, or contributes to, liver cell injury in alpha-1-ATZ deficiency. ..
  6. LOCAL EXPRESSION OF ALPHA-1-ANTITRYPSIN IN EMPHYSEMA
    David Perlmutter; Fiscal Year: 2005
    ....
  7. LOCAL EXPRESSION OF ALPHA-1-ANTITRYPSIN IN EMPHYSEMA
    David Perlmutter; Fiscal Year: 2003
    ..Lastly, the investigator proposes to determine whether there are tissue-specific differences in ER retention of a1-ATZ and the autophagic response in the lung and liver of PiZ mouse in vivo during homeostasis and inflammation. ..
  8. LOCAL EXPRESSION OF ALPHA-1-ANTITRYPSIN IN EMPHYSEMA
    David Perlmutter; Fiscal Year: 1993
    ..These studies have broad application to the understanding of this common genetic deficiency, consequent injury to lung and liver and to the development of new therapeutic strategies...
  9. LIVER INJURY IN ALPHA 1 ANTITRYPSIN DEFICIENCY
    David Perlmutter; Fiscal Year: 1999
    ....
  10. Hepatocellular Carcinoma in Antitrypsin Deficiency
    David H Perlmutter; Fiscal Year: 2010
    ..This knowledge will allow us to formulate novel strategies for treatment and prevention of liver cancer. ..
  11. Hepatocellular Carcinoma in Antitrypsin Deficiency
    David Perlmutter; Fiscal Year: 2009
    ..This knowledge will allow us to formulate novel strategies for treatment and prevention of liver cancer. ..
  12. The Clinical Interface of Molecular and Cellular Biology
    David Perlmutter; Fiscal Year: 2006
    ....
  13. Liver Injury in Alpha-1-Antitrypsin Deficiency
    David Perlmutter; Fiscal Year: 2005
    ..Thus, the studies proposed in this competitive renewal application will address the novel concept that oxidative stress causes, or contributes to, liver cell injury in alpha-1-ATZ deficiency. ..
  14. Novel Pharmacological Strategies for Liver Disease in Antitrypsin Deficiency
    David Perlmutter; Fiscal Year: 2009
    ....
  15. LOCAL EXPRESSION OF ALPHA-1-ANTITRYPSIN IN EMPHYSEMA
    David Perlmutter; Fiscal Year: 2006
    ....
  16. Screening for Genetic Mechanisms for Biliary Atresia
    David Perlmutter; Fiscal Year: 2006
    ..These studies will provide new information about and a basis for many additional studies of the pathogenesis, natural history, early diagnosis and treatment of BA, a rare and severe liver disease of infants ..
  17. Liver Injury in Alpha-1-Antitrypsin Deficiency
    David Perlmutter; Fiscal Year: 2007
    ..Thus, the studies proposed in this competitive renewal application will address the novel concept that oxidative stress causes, or contributes to, liver cell injury in alpha-1-ATZ deficiency. ..
  18. Molecular Basis of Pediatric Disease
    David Perlmutter; Fiscal Year: 2007
    ..These Scholars will be expected to establish Mentor Committees of four senior faculty scientists to advise and facilitate the development of their career. ..
  19. LOCAL EXPRESSION OF ALPHA-1-ANTITRYPSIN IN EMPHYSEMA
    David Perlmutter; Fiscal Year: 2007
    ....
  20. LOCAL EXPRESSION OF ALPHA-1-ANTITRYPSIN IN EMPHYSEMA
    David Perlmutter; Fiscal Year: 2004
    ....
  21. Liver Injury in Alpha-1-Antitrypsin Deficiency
    David Perlmutter; Fiscal Year: 2004
    ..Thus, the studies proposed in this competitive renewal application will address the novel concept that oxidative stress causes, or contributes to, liver cell injury in alpha-1-ATZ deficiency. ..
  22. LOCAL EXPRESSION OF ALPHA-1 ANTITRYPSIN IN EMPHYSEMA
    David Perlmutter; Fiscal Year: 1999
    ....
  23. LOCAL EXPRESSION OF ALPHA-1-ANTITRYPSIN IN EMPHYSEMA
    David Perlmutter; Fiscal Year: 2000
    ..Lastly, the investigator proposes to determine whether there are tissue-specific differences in ER retention of a1-ATZ and the autophagic response in the lung and liver of PiZ mouse in vivo during homeostasis and inflammation. ..
  24. LIVER INJURY IN ALPHA 1 ANTITRYPSIN DEFICIENCY
    David Perlmutter; Fiscal Year: 2000
    ....
  25. LOCAL EXPRESSION OF ALPHA-1-ANTITRYPSIN IN EMPHYSEMA
    David Perlmutter; Fiscal Year: 2001
    ..Lastly, the investigator proposes to determine whether there are tissue-specific differences in ER retention of a1-ATZ and the autophagic response in the lung and liver of PiZ mouse in vivo during homeostasis and inflammation. ..
  26. LOCAL EXPRESSION OF ALPHA-1-ANTITRYPSIN IN EMPHYSEMA
    David Perlmutter; Fiscal Year: 2002
    ..Lastly, the investigator proposes to determine whether there are tissue-specific differences in ER retention of a1-ATZ and the autophagic response in the lung and liver of PiZ mouse in vivo during homeostasis and inflammation. ..
  27. Liver Injury in Alpha-1-Antitrypsin Deficiency
    David Perlmutter; Fiscal Year: 2003
    ..Thus, the studies proposed in this competitive renewal application will address the novel concept that oxidative stress causes, or contributes to, liver cell injury in alpha-1-ATZ deficiency. ..
  28. LOCAL EXPRESSION OF ALPHA-1-ANTITRYPSIN IN EMPHYSEMA
    David Perlmutter; Fiscal Year: 2001
    ..Lastly, the investigator proposes to determine whether there are tissue-specific differences in ER retention of a1-ATZ and the autophagic response in the lung and liver of PiZ mouse in vivo during homeostasis and inflammation. ..
  29. LOCAL EXPRESSION OF ALPHA-1-ANTITRYPSIN IN EMPHYSEMA
    David Perlmutter; Fiscal Year: 1992
    ..These studies have broad application to the understanding of this common genetic deficiency, consequent injury to lung and liver and to the development of new therapeutic strategies...
  30. LOCAL EXPRESSION OF ALPHA-1-ANTITRYPSIN IN EMPHYSEMA
    David Perlmutter; Fiscal Year: 1991
    ..These studies have broad application to the understanding of this common genetic deficiency, consequent injury to lung and liver and to the development of new therapeutic strategies...