Perlmutter Lab

David Perlmutter is internationally recognized for his research on the pathobiology of α1-antitrypsin deficiency, a rare disease in which a misfolded protein causes chronic liver failure and hepatocellular carcinoma. His work has led to advances in understanding the basic mechanisms of liver fibrosis and carcinoma and novel therapeutic strategies. Together with collaborators he has discovered a pipeline of drugs that can eliminate misfolded proteins and reverse the liver disease in model organisms. One of these drugs has advanced to phase II/III clinical trials. The class of drugs may also be utilized for other diseases caused by misfolded proteins, including Alzheimer’s disease and other age-dependent degenerative diseases.

Principal investigator

David Perlmutter, MD

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

• Phone: 314-362-6837
• Email: perlmutterd@wustl.edu

Recent publications

• Regulation of PGC1α Downstream of the Insulin Signaling Pathway Plays a Role in the Hepatic Proteotoxicity of Mutant α1-Antitrypsin Deficiency Variant Z
  July 1, 2022
  Regulation of PGC1α Downstream of the Insulin Signaling Pathway Plays a Role in the Hepatic Proteotoxicity of Mutant α1-Antitrypsin Deficiency Variant ZRudnick, D. A., Huang, J., Hidvegi, T., Chu, A. S., Hale, P., Munanairi, A., Dietzen, D. J., Cliften, P. F., Tycksen, E., Lutkewitte, A. J., Finck, B. N., Pak, S. C., Silverman, G. A. & Perlmutter, D. H., Jul 2022, In: Gastroenterology. 163, 1, p. 270-284 15 p.Research output: Contribution to journal › Article › peer-review
• Mechanisms of action of autophagy modulators dissected by quantitative systems pharmacology analysis
  April 1, 2020
  Mechanisms of action of autophagy modulators dissected by quantitative systems pharmacology analysisShi, Q., Pei, F., Silverman, G. A., Pak, S. C., Perlmutter, D. H., Liu, B. & Bahar, I., Apr 1 2020, In: International journal of molecular sciences. 21, 8, 2855.Research output: Contribution to journal › Article › peer-review
• Identification of Polycystic Kidney Disease 1 Like 1 Gene Variants in Children With Biliary Atresia Splenic Malformation Syndrome
  September 1, 2019
  Identification of Polycystic Kidney Disease 1 Like 1 Gene Variants in Children With Biliary Atresia Splenic Malformation Syndromefor the Childhood Liver Disease Research Network (ChiLDReN), Sep 2019, In: Hepatology. 70, 3, p. 899-910 12 p.Research output: Contribution to journal › Article › peer-review
• NFκB mitigates the pathological effects of misfolded α1-antitrypsin by activating autophagy and an integrated program of proteostasis mechanisms
  March 1, 2019
  NFκB mitigates the pathological effects of misfolded α1-antitrypsin by activating autophagy and an integrated program of proteostasis mechanismsMukherjee, A., Hidvegi, T., Araya, P., Ewing, M., Stolz, D. B. & Perlmutter, D. H., Mar 1 2019, In: Cell Death and Differentiation. 26, 3, p. 455-469 15 p.Research output: Contribution to journal › Article › peer-review
• An analog of glibenclamide selectively enhances autophagic degradation of misfolded α1-antitrypsin Z
  January 1, 2019
  An analog of glibenclamide selectively enhances autophagic degradation of misfolded α1-antitrypsin ZWang, Y., Cobanoglu, M. C., Li, J., Hidvegi, T., Hale, P., Ewing, M., Chu, A. S., Gong, Z., Muzumdar, R., Pak, S. C., Silverman, G. A., Bahar, I. & Perlmutter, D. H., Jan 2019, In: PloS one. 14, 1, e0209748.Research output: Contribution to journal › Article › peer-review