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Daniel N. Hebert

Professor

Office

LSL N327
(413) 545-0079

Focus

Protein folding, quality control and degradation of membrane glycoproteins

Background and Training

PhD: University of Massachusetts Medical Center
Postdoctoral training: Yale University School of Medicine

Research Summary

The focus of my laboratory is to understand the processes involved in the maturation and degradation of proteins that traverse the secretory pathway in the living cell. 

Protein maturation is a highly assisted process enlisting the help of many cellular factors. We are particularly interested in understanding the role of co-translational folding and modifications that occur in the endoplasmic reticulum, and the involvement of molecular chaperones in these processes. The cell also possesses a quality control system that helps to ensure that only properly folded and assembled proteins are generated. Proteins that are unable to reach their native conformation are targeted for destruction. As our knowledge of protein maturation and quality control increases, it has become clear that a number of common human genetic diseases involve protein maturation defects including cystic fibrosis, albinism, melanoma and heart disease. Current model proteins that our laboratory studies include: tyrosinase, the key protein in melanin synthesis or cellular pigmentation; and the flu viral glycoprotein, hemagglutinin. We employ a variety of cell biololgical, biochemical, and molecular biological approaches to study the maturation and degradation of membrane glycoproteins using cell-free asssays, isolated organelles and live cells.

Figure 1. Model of the maturation and degradation pathway of the membrane glycoprotein, tyrosinase.

Publications

Raghava S, Giorda KM, Romano FB, Heuck AP, Hebert D.  (2011) The SV40 Late Protein VP4 Is a Viroporin that Forms Pores to Disrupt Membranes for Viral Release. PLoS Pathog. Jun;7(6):e1002116. Epub 2011 Jun 30. [PubMed]
     
Tamura T, Cormier JH, Hebert DN. (2011) Characterization of early EDEM1 maturation events and their functional implications. J Biol Chem. Jun 1. [PubMed]

Tamura T, Sunryd JC, Hebert DN. (2010) Sorting things out through endoplasmic reticulum quality control. Mol Membr Biol. Nov;27(8):412-27. [PubMed]
     
Pearse BR, Tamura T, Sunryd JC, Grabowski GA, Kaufman RJ, Hebert DN. (2010) The role of UDP-Glc:glycoprotein glucosyltransferase1 in the maturation of an obligate substrate prosaposin. J Cell Biol. May 31;189(5):829-41. [PubMed]
     
Hebert DN, Bernasconi R, Molinari M. (2010) ERAD substrates: which way out? Semin Cell Dev Biol. Jul;21(5):526-32. Epub 2009 Dec 22. [PubMed]

Pearse BR, Hebert DN. (2010) Lectin chaperones help direct the maturation of glycoproteins in the endoplasmic reticulum. Biochim Biophys Acta. Jun;1803(6):684-693. [PubMed]

Cyr DM, Hebert DN. (2009) Protein quality control--linking the unfolded protein response to disease. Conference on 'From Unfolded Proteins in the Endoplasmic Reticulum to Disease'. EMBO Rep. Nov;10(11):1206-10. [PubMed]

A. Jejcic, R. Daniels, L. Goobar-Larsson, D.N. Hebert, A.Vahlne. (2009) Small molecule targets Env for ER-associated protein degradation and inhibits HIV-1 propagation. J Virol. Oct;83(19):10075-84. [PubMed]

D.N. Hebert , L.M. Gierasch. (2009) The molecular dating game: an antibody heavy chain hangs loose with a chaperone while waiting for its life partner. Molecular Cell. Jun 26;34(6):635-6. [PubMed]

J. H. Cormier , Tamura T., J.C, Sunryd, D.N. Hebert. (2009) EDEM1 recognition and delivery of misfolded proteins to the SEL1L-containing ERAD complex. Molecular Cell. Jun 12;34(5):627-33. [PubMed]

Wang, N., E.J. Glidden, S.R. Murphy, B.R. Pearse, and D.N. Hebert. (2008). The co-translational maturation program for the type II membrane glycopotein influenza neuraminidase. J Biol Chem. 283(49):33826-37. [PubMed]

Tamura, T., J.H. Cormier, and D.N. Hebert. Sweet Bays of ERAD. (2008). Trends Biochem Sci. Jul;33(7):298-300. [PubMed]

Pearse, B.R., L. Gabriel, N. Wang, and D.N. Hebert. (2008). A cell-based reglucosylation assay demonstrates the role of GT1 in the quality control of a maturing glycoprotein. J Cell Biol. 181: 309-320. [PubMed]

Hebert, D.N. and M. Molinari. (2007). In and out of the ER: protein folding, quality control and degradation, and related human diseases. Physiology Reviews. 87(4): p. 1377-1408. [PubMed]
 
Hebert, D.N. (2007). Glycoprotein maturation and quality control in the endoplasmic reticulum. [Audio Lecture]. Henry Stewart talks lecture series on the Endoplasmic Reticulum: Fundamentals and role in disease. London, UK. Series editor M. Michalak. (online at http://hstalks.com/bio)

Pearse, B. R. and D. N. Hebert. (2007). Calnexin, Calreticulin and their associated oxidoreductase ERp57. The Enzymes, Vol. 25, Molecular Machines involved in Protein Transport across Cellular Membranes, Edited by R. E. Dalbey, C. Koehler and F. Tamanoi for Academic Press/Elsevier. August 2007.

Daniels, R., D. Sadowicz., and D.N. Hebert. (2007) A Very Late Viral Protein Triggers the Lytic Release of SV40. PLOS Pathogens. 3(7). [PubMed]

Wang N, Hebert DN. (2006) Tyrosinase maturation through the mammalian secretory pathway: bringing color to life. Pigment Cell Research. February; 19 (1): 3-18. [PubMed]

Cormier JH, Pearse BR, Hebert DN. (2005) Yos9p: a sweet-toothed bouncer of the secretory pathway. Mol Cell. 19(6):717-9. [PubMed]

Wang N, Daniels R, Hebert DN. (2005) The cotranslational maturation of the type I membrane glycoprotein tyrosinase: the heat shock protein 70 system hands off to the lectin-based chaperone system. Mol Biol Cell. 16(8):3740-52. [PubMed]

Hebert DN, Garman SC, Molinari M. The glycan code of the endoplasmic reticulum: asparagine-linked carbohydrates as protein maturation and quality-control tags. Trends Cell Biol. 2005 Jul;15(7):364-70. Review. [PubMed]

Daniels R, Svedine S, Hebert DN. N-linked carbohydrates act as lumenal maturation and quality control protein tags. Cell Biochem Biophys. 2004;41(1):113-38. [PubMed]

Svedine S, Wang T, Halaban R, Hebert DN. Carbohydrates act as sorting determinants in ER-associated degradation of tyrosinase. J Cell Sci. 2004 Jun 15;117(Pt 14):2937-49. Epub 2004 May 25. [PubMed]