Daniel N. Hebert

Professor of Biochemistry and Molecular Biology, University of Massachusetts

Email: dhebert@biochem.umass.edu
D. Hebert Biochemistry & Molecular Biology Web Site
D. Hebert Lab Web Site

Ph.D.: University of Massachusetts Medical Center
Postdoctoral Training: Yale University School of Medicine

Protein Folding, Quality Control and Degradation of Membrane Glycoproteins

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.

Representative publications:

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 in press.

Braakman, I. and Hebert, D.N. (2012) "Protein folding in the endoplasmic reticulum", in Ferro-Novick, S.R. Schekman, and T. Rapoport (ed.), Endoplasmic Reticulum Monograph, Cold Spring Harbor Laboratory Press, in press.

Hebert, D.N. (2012), "The ERAD Network", in Houry, W. (ed.), Protein Homeostasis, The Biomedical & Life Sciences Collection, Henry Stewart Talks Ltd, London (online at http://hstalks.com/?t=BL1423153-Hebert)

Hebert D.N. (2012), An MBoC Favorite: Malectin: a novel carbohydrate-binding protein of the endoplasmic reticulum and a candidte player in the early steps of protein N-glycosylation. Molecular Biology of the Cell 23(12):2236.

Giorda KM, Raghava S, Hebert DN. The Simian virus 40 late viral protein VP4 disrupts the nuclear envelope for viral release. J Virol. 2012 Mar;86(6):3180-92.

Tamura, T., J. H. Cormier and D.N. Hebert (2011) Characterization of the early EDEM1 maturation events and their functional implications. Journal of Biological Chemistry, 286(28):24906-15.

Raghava, S., K.M. Giorda, F.B. Romano, A.P. Heuck and D.N. Hebert (2011) Th SV40 late protein VP4 is a viroporin that formes pores to disrupt membranes viral release, PLoS Pathogens, 7(6):1002116.

Tamura, T., J.C. Sunryd and D.N. Hebert (2010) Sorting things out through ER quality control, Molecular Membranes Biology, 27(8):412-427.

Pease, B.R., T, Tamura, J.C. Sunryd, G.A. Grabowski, R.J. Kaufman and D.N. Hebert (2010) The role of UDP-Glc:glycoprotein glucosyltransferase 1 in the maturation of an obligate substrate, prosaposin, Journal of Cell Biology, 189:829-841.

Hebert, D.N., R. Bernasconi and M. Molinari (2010) ERAD substrates: which way out? Seminar in Cell and Developmental Biology, 21:526-532.

Pearse, B.R. and D.N. Hebert (2010) Lectin chaperones help direct maturation of glycoproteins in the endoplasmic reticulum, Biochimica et Biophysica Acta, 1803:684-693.

Cyr, D.M. and D.N. Hebert (2009) Protein Quality Control: A Meeting on Links Between the Unfolded Protein Response and Disease, EMBO Reports, 10(11):1206-10.

Jejcic, A., R. Daniels, L. Goodbar-Larsson, D.N. Hebert, and A. Vahlne (2009) Small Molecule targets Env for ER-associated protein degradation and inhibits HIV-1 propagation. Journal of Virology 83(19):10075-84.

Hebert, D.N. and L.M.Gierasch (2009) The molecular dating game: an antibody heavy chain hangs loose with a chaperone while waiting for its life partner. [Preview] Molecular Cell 34:635-636.

Cormier, J.H., T. Tamura and D.N. Hebert (2009) EDEM1 recognition and delivery of misfolded proteins to the SEL 1L-containing ERAD complex. Molecular Cell 34:627-633.

Wang, N., E.J. Glidden, S.R. Murphy, B.R. Pearse and D.N. Hebert (2008) The cotranslational maturation program for the type II membrane glycoprotein influenza neuraminidase. Journal of Biological Chemistry 283:33826-33837.

Tamura, T., J. H. Cormier and D.N. Hebert (2008) Sweet bays of ERAD. Trends in Biochemical Sciences 33:298-300.

Pearse B.R., L. Gabriel, N. Wang and D.N. Hebert (2008) A cell-based reglucosylation assay demonstrates the role of GR1 in th quality control of a maturing glycoprotein. Journal of Cell Biology 181:309-320.