Amy S. Lee

PIBBS MENTOR

Professor

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 my laboratory is to investigate the regulation and function of two stress-inducible proteins GRP78/BiP and GRP94. As Ca2+-binding molecular chaperones localized in the endoplasmic reticulum (ER), they play important roles in protein folding, secretion, and can confer protection against cell death under a variety of stress conditions. In tumor cells, induction of the GRPs confers resistance to cell mediated cytotoxicity and leads to tumor progression. Since stress in the ER such as Ca2+-depletion or protein malfolding can activate the Grp78 and Grp94 promoters, the GRP system offers a unique model to study intra-organelle signaling. We have deciphered the genetic code for the coordinate induction of the GRP genes and identified the transcription factors which mediate the ER stress response. We plan to investigate further into the role of chromatin and transcription factor modifications that regulate Grp promoter activity. We also found that GRP induction in solid tumors confer drug resistance to cancer cells. We have constructed conditional knockout models for the study of the physiological function of GRP78 and GRP94 in vivo. In particular, we will examine the requirement of GRP78 and GRP94 for tumor proliferation, survival and metastasis. Our laboratory has also discovered new mouse models of diabetes and obesity resulting from novel disruption of ER gene function. Future studies will use these models to understand the role of the GRP stress proteins in development and pathophysiology of human diseases.

Research in Progress:

1) To investigate the function and regulation of the stress-inducible glucose regulated protein genes in mammalian cells using conditional knockout mouse models.

2) To investigate the functional contribution of the glucose regulated protein in cancer progression and drug resistance.

3) To investigate the link of ER stress to cancer and metabolic diseases such as diabetes and obesity.

Postdoctoral Position Available

Interested candidate, please contact Dr. Lee at
amylee@usc.edu