| Send E-mail to: amylee@usc.edu | |
| Telephone: 323-865-0507 | Fax: 323-865-0094 |
| Office: NOR 5307 | Mail Code: 9176 HSC |
Education:
BA 1970 Bacteriology & Immunology - University of California at Berkeley, California
MS 1972 Biology - California Institute of Technology, California
PhD 1975 Biology - California Institute of Technology, California
Postdoctoral Research Fellowship:
1975-1978 California Institute of Technology, Pasadena
Started at USC: 1979
Research Topics: Cancer Cell Biology, Gene Regulation/Transcription, Gene Therapy, Human/Mammalian Genetics
Research Description
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.
Selected Publications
Li J, Ni M, Lee B, Barron E, Hinton DR, Lee AS. - The unfolded protein response regulator GRP78/BiP is required for endoplasmic reticulum integrity and stress-induced autophagy in mammalian cells. - Cell Death Differ [ 2008 ] Jun 13; . PubMed
Dong D, Ni M, Li J, Xiong S, Ye W, Virrey JJ, Mao C, Ye R, Wang M, Pen L, Dubeau L, Groshen S, Hofman FM, Lee AS. - Critical role of the stress chaperone GRP78/BiP in tumor proliferation, survival, and tumor angiogenesis in transgene-induced mammary tumor development. - Cancer Res [ 2008 ] Jan 15;68(2):498-505 . PubMed
Pyrko P, Schönthal AH, Hofman FM, Chen TC, Lee AS. - The unfolded protein response regulator GRP78/BiP as a novel target for increasing chemosensitivity in malignant gliomas. - Cancer Res [ 2007 ] Oct 15;67(20):9809-16 . PubMed
Daneshmand S, Quek ML, Lin E, Lee C, Cote RJ, Hawes D, Cai J, Groshen S, Lieskovsky G, Skinner DG, Lee AS, Pinski J. - Glucose-regulated protein GRP78 is up-regulated in prostate cancer and correlates with recurrence and survival. - Hum Pathol [ 2007 ] Oct;38(10):1547-52 . PubMed
Bánhegyi G, Baumeister P, Benedetti A, Dong D, Fu Y, Lee AS, Li J, Mao C, Margittai E, Ni M, Paschen W, Piccirella S, Senesi S, Sitia R, Wang M, Yang W. - Endoplasmic reticulum stress. - Ann N Y Acad Sci [ 2007 ] Oct;1113:58-71 . PubMed
Ni M, Lee AS. - ER chaperones in mammalian development and human diseases. - FEBS Lett [ 2007 ] Jul 31;581(19):3641-51 . PubMed
Fu Y, Li J, Lee AS. - GRP78/BiP inhibits endoplasmic reticulum BIK and protects human breast cancer cells against estrogen starvation-induced apoptosis. - Cancer Res [ 2007 ] Apr 15;67(8):3734-40 . PubMed
Lee AS. - GRP78 induction in cancer: therapeutic and prognostic implications. - Cancer Res [ 2007 ] Apr 15;67(8):3496-9 . PubMed
Pootrakul L, Datar RH, Shi SR, Cai J, Hawes D, Groshen SG, Lee AS, Cote RJ. - Expression of stress response protein Grp78 is associated with the development of castration-resistant prostate cancer. - Clin Cancer Res [ 2006 ] Oct 15;12(20 Pt 1):5987-93 . PubMed
Gal-Yam EN, Jeong S, Tanay A, Egger G, Lee AS, Jones PA. - Constitutive nucleosome depletion and ordered factor assembly at the GRP78 promoter revealed by single molecule footprinting. - PLoS Genet [ 2006 ] Sep 22;2(9):e160 . PubMed
