Endoplasmic Reticulum

Novel Therapeutics Targeting ER Associated Degradation (ERAD)

There has been a recent explosion in the number of identified disorders linked to protein misfolding in the endoplasmic reticulum (ER), resulting in ER entrapment and degradation of exportable proteins. Several approaches have been proposed for potential therapies, including pharmacological modification of the rate of protein synthesis to avoid protein folding overload, manipulation of the ER ionic milieu, use of pharmacologic chaperones or modulators of endogenous ER chaperone activities, or pre-emptive induction of the Unfolded Protein Response.

Each of these therapies is designed to manipulate the ER quality control environment and improve the protein folding capacity while diminishing the protein folding load. However, none of these existing therapies has yet proved broadly efficacious. We will explore critical factors regulating ERAD and ER proteostasis with the goal of identifying new therapeutic targets for disorders related to protein misfolding in the ER.

Investigators Involved with this Hub:

ER Calcium Subgroup

ER Redox Subgroup

Hub Publications:

Walczak C, Ravindran MS, Inoue T, Tsai B.  A Cytosolic Chaperone Complexes with Dynamic Membrane J-Proteins and Mobilizes a Nonenveloped Virus out of the Endoplasmic Reticulum.  PLOS Pathogens. 2014 March 27.
Liu M.  Inefficient Translocation of Perproinsuline Contributes to Pancreatic Beta Cell Failure and Late Onset Diabetes.  Journal of Biological Chemistry, in press.


NIH, RO1 DK040344, Thyrocyte protein transport to the cell surface, Peter Arvan
NIH, RO1 DK48280, Peptide Hormone Sorting to the Secretory/Storage Granule, Peter Arvan