Amy S. Lee



Biochemistry & Molecular Biology
Keck School of Medicine
USC Norris Comprehensive Cancer Center

Research Topics

  • Cancer Cell Biology
  • Gene Regulation/Transcription
  • Gene Therapy
  • Human/Mammalian Genetics

Research Images

Research Overview

The major research focus of the Lee laboratory is in the area of endoplasmic reticulum (ER) stress and, in particular, the ER chaperone proteins, GRP78 and GRP94. As Ca2+-binding molecular chaperones, they play important roles in the folding and processing of membrane associated and secretory proteins, many of which control key functions in cell growth, adhesion and cellular communication. With the recent discovery that these GRPs can relocate to the cell surface in stressed cells, this opens up novel functions of the GRPs beyond the ER, including regulation of critical oncogenic signaling from the cell surface.

The Lee laboratory is the first to clone human GRP78 and elucidate its transcriptional regulation, an essential role in regulating cellular homeostasis and its requirement for mammalian development, as well as cancer progression and therapeutic resistance. We have created expression vectors and mouse models genetically targeting GRP78 and GRP94 that provide valuable tools to ascertain its functional role in health and disease state. Our laboratory has established the anti-apoptotic properties of GRP78 and its critical role in cancer progression and therapeutic resistance. In cell metabolism, through creating genetic knockout mouse models of GRP78, we obtained direct evidence that GRP78 deficiency could have substantial impact on adiposity and response to diet-induced diabetes and pancreatitis. We also discovered the requirement of GRP78 for maintaining ER integrity and autophagy. Recently, our research has expanded into investigating the role of GRP78 beyond the ER through control of signaling pathways by GRP78 that are localized to the cell surface. Our laboratory is currently developing and testing therapeutics targeting GRP78 for application into cancer and other human diseases.

Postdoctoral Position Available

Interested candidate, please contact Dr. Lee at