LSL N327


Protein folding, quality control and degradation of glycoproteins

Background and Training

PhD: University of Massachusetts Medical Center

Postdoctoral training: Yale University School of Medicine

Research Summary

A labeled diagram of N-linked glycans as protein sorting tags in the endoplasmic reticulum.
Figure 1. N-linked glycans as protein
sorting tags in the endoplasmic
reticulum (Hebert et al., 
Nature Chemical Biology 2014)

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.

Hebert Research Group


  • Adams, B. M., M. E. Oster and D. N. Hebert (2019) Protein quality control in the endoplasmic reticulum. The Protein Journal 38(3):317-329.
  • Graham, J. B., N. P. Canniff and D. N. Hebert (2019) TPR containing proteins control protein organization and homeostasis in the endoplasmic reticulum. Critical Reviews in Molecular and Cellular Biology 54(2):103-118.
  • Lamriben L, Oster ME, Tamura T, Tian W, Yang Z, Clausen H, and D. N. Hebert (2018) EDEM1's mannosidase-like domain binds ERAD client proteins in a redox-sensitive manner and possesses catalytic activity. Journal of Biological Chemistry. 293(36):13932-13945.
  • Lamriben, L. and D. N. Hebert (2018) Activating and repressing IRE1a: The Hsp47 and BiP Tug of War, Mol. Cell 69(2):159-160.    
  • Krishnan, B., L. Hedstrom, D. N. Hebert, L. M. Gierasch, and A. Gershenson, (2017) Expression and purification of active recombinant human a1-antitrypsin. Methods Mol Biol. 1639: 195-209.
  • Braakman, I., L. Lamriben, G. van Zadelhoff and D. N. Hebert (2017) Analysis of disulfide bond formation overview. In Current protocols in protein science, J. E. Coligan, H.L. Ploegh, J. A. Smith, D. W. Speicher and P.T. Wingfield, eds. (Brooklyn, NY: Greene Publ. Assoc. and Wiley-Interscience.
  • Chandrasekhar K., H. Ke, N. Wang, T. Goodwin, L.M. Gierasch, A. Gershenson, D. N. Hebert (2016) Cellular folding pathway of a metastable serpin. Proc. Natl. Acad. Sci. USA 113(23):6484-9. [PubMed]
  • Lamriben L., J. B. Graham, B. M. Adams, and D. N. Hebert, (2016) N-glycan based ER molecular chaperone and protein quality control system: the calnexin binding cycle. Traffic. 17(4):308-26. [PubMed]
  • Tannous A., G. B. Pisoni, D. N. Hebert and M. Molinari. (2015) N-linked sugar regulated protein folding and quality control in the ER, Seminars in Cell and Developmental Biology, 41:79-89[PubMed]
  • Tannous A., N. Patel, T. Tamura, and D. N. Hebert. (2015) Reglucosylation by UDP-glucose: glycoprotein glucosyltransferase 1 delays glycoprotein secretion but not degradation. Molecular Biology of the Cell, 26(3):390-405. [PubMed]
  • Guiliano, D.B, H. Fussell, I. Lenart, E. Tsao, D. Nesbeth, A. Fletcher, E. C. Campbell, S. Lynch, S. Santos, A. Cameron, G. Towers, P. Kellam, D. N. Hebert, K. Gould, S. J. Powis, and A. N. Antoniou. (2014) HLA-B27 dimers preferentially interact with EDEM1 and are targeted for degradation by an HRD1-dependent pathway. Arthritis & Rheumatology, 66(11):2976-88. [PubMed]
  • Hebert, D. N., L. Lamriben, E. T. Powers# and J. W. Kelly. (2014) The intrinsic and extrinsic effects of N-linked glycans on glycoproteostasis. Nature Chemical Biology, 10(11):902-910. [PubMed]
  • Sunryd, J.C., B. Cheon, J. B. Graham, K. M. Giorda, R. A. Fissore, D. N. Hebert. (2014) TMTC1 and TMTC2 are novel endoplasmic reticulum TPR-containing adapter proteins involved in calcium homeostasis. Journal of Biological Chemistry. 289:16085-16099. [PubMed]
  • Sunryd, J. C., T. Tannous, L. Lamriben and D. N. Hebert (2014) Chaperones of the ERAD pathway. In W. A. Houry (ed.), The Molecular Chaperones Interaction Networks in Protein Folding and Degradation, Springer Press
  • Giorda KM, Hebert DN. (2013) Viroporins customize host cells for efficient viral propagation. DNA & Cell Biol. 2013 Oct;32(10):557-64. [PubMed]
  • Raghava, S., K. M. Giorda, F. B. Romano, A. P. Heuck and D. N. Hebert (2013) SV40 late protein VP4 forms toroidal pores to disrupt membranes for viral release. Biochemistry. 2013 Jun 4;52(22):3939-48. [PubMed]
  • Giorda, K. M., S. Raghava, M. W. Zhang and D. N. Hebert (2013) The viroporin activity of the minor structural proteins VP2 and VP3 is required for SV40 propagation. Journal of Biological Chemistry, 288(4):2510-2520. [PubMed]
  • Braakman, I. and D. N. Hebert (2013) “Protein folding in the endoplasmic reticulum”, in Ferro-Novick, S, R. Schekman, and T. Rapoport (ed.), Endoplasmic Reticulum Monograph, Cold Spring Harbor Laboratory Press. May 1;5(5):a013201. [PubMed]
  • Hebert, D. N. and M. Molinari# (2012) Flagging and Docking: dual roles for N-glycans in protein quality control and cellular proteostasis. Trends in Biochemical Sciences 37(10):404-410. [PubMed]