A BiP-centric View of Endoplasmic Reticulum Functions and of My Career

Abstract

After completing my post-doctoral training at the University of Alabama, Birmingham and a brief period on the faculty there, I joined the Department of Tumor Cell Biology at St. Jude Children’s Research Hospital in 1987 as an Assistant Member and started my independent research program. For the following 37 years, I led a relatively small basic research group comprised at various times of post-doctoral fellows, graduate students, undergraduate students, and research technicians; many of whom I am still in contact. Last year I closed the lab and transitioned to an emeritus position at St. Jude. I continue to maintain several research collaborations covering areas of research that have long been dear to my heart.

My post-doctoral studies on BiP revealed that it controlled immunoglobulin assembly and transport, and as such, played a critical role in the fidelity of the immune response. My lab continued to define BiP’s functions in protein folding and subunit assembly, as well as, in degradation of proteins that failed to mature properly using biochemical, cell-based, and biophysical analyses. Several ER localized co-factors that regulate the activity of BiP and allow it to contribute to its multiple ER functions were identified by our group. These include DnaJ family members and nucleotide change factors. Through a variety of collaborative studies, we pursued BiP’s functions in maintaining the permeability barrier of the translocon, contributing to ER calcium stores, and regulating the up-stream transducers of the UPR, a stress response that is activated by the accumulation of unfolded proteins in the ER.