Faculty

Amy Shiu Lee, PhD
Amy Shiu Lee, PhD
Professor of Biochemistry & Molecular Medicine;Judy and Larry Freeman Chair in Basic Science Cancer Research
Biochemistry and Molecular Medicine
NOR 5306, 5310, 5312, 5314, 5338, 1441 Eastlake Avenue Health Sciences Campus Los Angeles
Dr. Amy Lee is the Associate Director for Basic Research and Professor of Biochemistry and Molecular Medicine at the University of Southern California (USC) Norris Comprehensive Cancer Center, Los Angeles, California. Dr. Lee obtained her B.A. from the University of California, Berkeley, and her Ph.D. from the California Institute of Technology, Pasadena, California. Dr. Lee is currently holder of the Judy and Larry Freeman Cosmetics Chair in Basic Science in Cancer Research at USC. Dr. Lee’s research focuses on the mammalian stress response and molecular chaperones. Her laboratory is the first to clone the genes coding for a set of endoplasmic reticulum (ER) stress-inducible glucose regulated proteins (GRPs) and has made numerous discoveries in understanding how these genes are regulated and their role in development and human diseases. Dr. Lee’s laboratory established that GRP78 is a major contributor for tumorigenesis, metastatic growth and drug resistance. Through creation of conditional mouse models of GRP78, her laboratory provides direct proof that partial reduction of GRP78, while having no effect on normal organ function, is sufficient to halt cancer progression in vivo. GRP78 is now recognized as a novel cancer therapeutic target with dual function in tumor progression as well as tumor angiogenesis and a novel prognostic marker for tumor virulence and disease recurrence. With the recent discovery that GRP78 is preferentially expressed on the cell surface of tumor cells controlling signaling and proliferation, her laboratory is investigating the basic mechanisms for GRP translocation to the cell surface and developing therapeutics targeting the GRPs for clinical applications.

For her research achievements, Dr. Lee received the MERIT Award from the National Cancer Institute. In recognition of her pioneering work on ER stress and its impact on cell and cancer biology, she was elected Fellow of the American Association for the Advancement of Sciences (AAAS).

Cell Stress Society International : Spirit of Budapest Pioneer Award, 2019

Indiana University School of Medicine: The Mark Brothers Award, 2019

University of Southern California: Associates Award for Creativity in Research and Scholarship, 2018

Glucose-regulated protein 78 is essential for cardiac myocyte survival Cell Death Differ. 2018 12; 25(12):2181-2194. . View in PubMed

Endoplasmic reticulum chaperone GRP78 regulates macrophage function and insulin resistance in diet-induced obesity FASEB J. 2018 04; 32(4):2292-2304. . View in PubMed

Endoplasmic reticulum stress activates SRC, relocating chaperones to the cell surface where GRP78/CD109 blocks TGF-ß signaling Proc Natl Acad Sci U S A. 2018 05 01; 115(18):E4245-E4254. . View in PubMed

Effects of Prolonged GRP78 Haploinsufficiency on Organ Homeostasis, Behavior, Cancer and Chemotoxic Resistance in Aged Mice Sci Rep. 2017 02 01; 7:40919. . View in PubMed

GRP78 haploinsufficiency suppresses acinar-to-ductal metaplasia, signaling, and mutant Kras-driven pancreatic tumorigenesis in mice Proc Natl Acad Sci U S A. 2017 05 16; 114(20):E4020-E4029. . View in PubMed

Glucose-regulated protein 94 deficiency induces squamous cell metaplasia and suppresses PTEN-null driven endometrial epithelial tumor development Oncotarget. 2016 Mar 22; 7(12):14885-97. . View in PubMed

GRP94 Regulates Circulating Cholesterol Levels through Blockade of PCSK9-Induced LDLR Degradation Cell Rep. 2015 Dec 15; 13(10):2064-71. . View in PubMed

ER Chaperone BiP/GRP78 Is Required for Myelinating Cell Survival and Provides Protection during Experimental Autoimmune Encephalomyelitis J Neurosci. 2015 Dec 02; 35(48):15921-33. . View in PubMed

Characterization and mechanism of stress-induced translocation of 78-kilodalton glucose-regulated protein (GRP78) to the cell surface J Biol Chem. 2015 Mar 27; 290(13):8049-64. . View in PubMed

ER stress induces epithelial differentiation in the mouse oesophagus Gut. 2015 Feb; 64(2):195-202. . View in PubMed

GRP78 as a regulator of liver steatosis and cancer progression mediated by loss of the tumor suppressor PTEN Oncogene. 2014 Oct 16; 33(42):4997-5005. . View in PubMed

Differential requirement of GRP94 and GRP78 in mammary gland development Sci Rep. 2014 Jun 23; 4:5390. . View in PubMed

Glucose-regulated proteins in cancer: molecular mechanisms and therapeutic potential Nat Rev Cancer. 2014 Apr; 14(4):263-76. . View in PubMed

Deficiency of GRP94 in the hematopoietic system alters proliferation regulators in hematopoietic stem cells Stem Cells Dev. 2013 Dec 01; 22(23):3062-73. . View in PubMed

AKT inhibition mitigates GRP78 (glucose-regulated protein) expression and contribution to chemoresistance in endometrial cancers Int J Cancer. 2013 Jul; 133(1):21-30. . View in PubMed

ER stress causes rapid loss of intestinal epithelial stemness through activation of the unfolded protein response Cell Rep. 2013 Apr 25; 3(4):1128-39. . View in PubMed

GRP78 plays an essential role in adipogenesis and postnatal growth in mice FASEB J. 2013 Mar; 27(3):955-64. . View in PubMed

Cancer cells resistant to therapy promote cell surface relocalization of GRP78 which complexes with PI3K and enhances PI(3,4,5)P3 production PLoS One. 2013; 8(11):e80071. . View in PubMed

GRP78/BiP is a novel downstream target of IGF-1 receptor mediated signaling J Cell Physiol. 2012 Dec; 227(12):3803-11. . View in PubMed

Endoplasmic reticulum stress response promotes cytotoxic phenotype of CD8aß+ intraepithelial lymphocytes in a mouse model for Crohn's disease-like ileitis J Immunol. 2012 Aug 01; 189(3):1510-20. . View in PubMed

A novel pathogenic role of the ER chaperone GRP78/BiP in rheumatoid arthritis J Exp Med. 2012 Apr 09; 209(4):871-86. . View in PubMed

Acute inducible ablation of GRP78 reveals its role in hematopoietic stem cell survival, lymphogenesis and regulation of stress signaling PLoS One. 2012; 7(6):e39047. . View in PubMed

GRP78 promoter polymorphism rs391957 as potential predictor for clinical outcome in gastric and colorectal cancer patients Ann Oncol. 2011 Nov; 22(11):2431-9. . View in PubMed

A critical role for GRP78/BiP in the tumor microenvironment for neovascularization during tumor growth and metastasis Cancer Res. 2011 Apr 15; 71(8):2848-57. . View in PubMed

Beyond the endoplasmic reticulum: atypical GRP78 in cell viability, signalling and therapeutic targeting Biochem J. 2011 Mar 01; 434(2):181-8. . View in PubMed

GRP78 as potential predictor for breast cancer response to adjuvant taxane therapy Int J Cancer. 2011 Feb 01; 128(3):726-31. . View in PubMed

Grp78 heterozygosity regulates chaperone balance in exocrine pancreas with differential response to cerulein-induced acute pancreatitis Am J Pathol. 2010 Dec; 177(6):2827-36. . View in PubMed

Cell surface relocalization of the endoplasmic reticulum chaperone and unfolded protein response regulator GRP78/BiP J Biol Chem. 2010 May 14; 285(20):15065-75. . View in PubMed

Essential role of the unfolded protein response regulator GRP78/BiP in protection from neuronal apoptosis Cell Death Differ. 2010 Mar; 17(3):488-98. . View in PubMed

Grp78 heterozygosity promotes adaptive unfolded protein response and attenuates diet-induced obesity and insulin resistance Diabetes. 2010 Jan; 59(1):6-16. . View in PubMed

Glucose-regulated protein 78 as a novel effector of BRCA1 for inhibiting stress-induced apoptosis Oncogene. 2008 Dec 04; 27(53):6782-9. . View in PubMed

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. . View in PubMed

Glucose-regulated protein GRP78 is up-regulated in prostate cancer and correlates with recurrence and survival Hum Pathol. 2007 Oct; 38(10):1547-52. . View in PubMed

ER chaperones in mammalian development and human diseases FEBS Lett. 2007 Jul 31; 581(19):3641-51. . View in PubMed

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. . View in PubMed

GRP78 induction in cancer: therapeutic and prognostic implications Cancer Res. 2007 Apr 15; 67(8):3496-9. . View in PubMed

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. . View in PubMed

Constitutive nucleosome depletion and ordered factor assembly at the GRP78 promoter revealed by single molecule footprinting PLoS Genet. 2006 Sep 22; 2(9):e160. . View in PubMed

GRP78 as a novel predictor of responsiveness to chemotherapy in breast cancer Cancer Res. 2006 Aug 15; 66(16):7849-53. . View in PubMed

GRP78/BiP is required for cell proliferation and protecting the inner cell mass from apoptosis during early mouse embryonic development Mol Cell Biol. 2006 Aug; 26(15):5688-97. . View in PubMed

ER stress and cancer Cancer Biol Ther. 2006 Jul; 5(7):721-2. . View in PubMed

Glucose regulated proteins in cancer progression, drug resistance and immunotherapy Cancer Biol Ther. 2006 Jul; 5(7):741-4. . View in PubMed

Activator protein-2 overexpression accounts for increased insulin receptor expression in human breast cancer Cancer Res. 2006 May 15; 66(10):5085-93. . View in PubMed

Endoplasmic reticulum stress-induced apoptosis: multiple pathways and activation of p53-up-regulated modulator of apoptosis (PUMA) and NOXA by p53 J Biol Chem. 2006 Mar 17; 281(11):7260-70. . View in PubMed

Endoplasmic reticulum stress induction of the Grp78/BiP promoter: activating mechanisms mediated by YY1 and its interactive chromatin modifiers Mol Cell Biol. 2005 Jun; 25(11):4529-40. . View in PubMed

Endoplasmic reticulum stress triggers an acute proteasome-dependent degradation of ATF6 J Cell Biochem. 2004 Jul 01; 92(4):723-32. . View in PubMed

ATF6 modulates SREBP2-mediated lipogenesis EMBO J. 2004 Feb 25; 23(4):950-8. . View in PubMed

Endoplasmic reticulum chaperone protein GRP78 protects cells from apoptosis induced by topoisomerase inhibitors: role of ATP binding site in suppression of caspase-7 activation J Biol Chem. 2003 Jun 06; 278(23):20915-24. . View in PubMed

Cancer-inducible transgene expression by the Grp94 promoter: spontaneous activation in tumors of various origins and cancer-associated macrophages Cancer Res. 2002 Dec 15; 62(24):7207-12. . View in PubMed

Enhanced photodynamic therapy efficacy with inducible suicide gene therapy controlled by the grp promoter Cancer Res. 2002 Mar 01; 62(5):1458-61. . View in PubMed

CDP and AP-2 mediated repression mechanism of the replication-dependent hamster histone H32 promoter. J Cell Biochem. 2002; 84(4):699-707. . View in PubMed

Heterogeneous nuclear ribonucleoproteins as regulators of gene expression through interactions with the human thymidine kinase promoter J Cell Biochem. 2000 Sep 07; 79(3):395-406. . View in PubMed

ATF6 as a transcription activator of the endoplasmic reticulum stress element: thapsigargin stress-induced changes and synergistic interactions with NF-Y and YY1 Mol Cell Biol. 2000 Jul; 20(14):5096-106. . View in PubMed

Eradication of murine mammary adenocarcinoma through HSVtk expression directed by the glucose-starvation inducible grp78 promoter Breast Cancer Res Treat. 2000 Jan; 59(1):81-90. . View in PubMed

Conservation and divergence of the yeast and mammalian unfolded protein responseActivation of specific mammalian endoplasmic reticulum stress element of the grp78/BiP promoter by yeast Hac1. J Biol Chem. 1999 Oct 22; 274(43):30402-9. . View in PubMed

De-regulation of GRP stress protein expression in human breast cancer cell lines Breast Cancer Res Treat. 1999 Mar; 54(2):135-46. . View in PubMed

Hepatitis C virus core protein interacts with heterogeneous nuclear ribonucleoprotein K J Biol Chem. 1998 Jul 10; 273(28):17651-9. . View in PubMed

Endoplasmic reticulum stress-inducible protein GRP94 is associated with an Mg2+-dependent serine kinase activity modulated by Ca2+ and GRP78/BiP J Cell Physiol. 1997 Feb; 170(2):115-29. . View in PubMed

Identification of a set of protein species approximately 40 kDa as high-affinity DNA binding factor(s) to the cell cycle regulatory region of the human thymidine kinase promoter Cell Growth Differ. 1996 Dec; 7(12):1741-9. . View in PubMed

Calcium-sensitive transcriptional activation of the proximal CCAAT regulatory element of the grp78/BiP promoter by the human nuclear factor CBF/NF-Y J Biol Chem. 1996 Nov 15; 271(46):28995-9002. . View in PubMed

Conformation-defective herpes simplex virus 1 glycoprotein B activates the promoter of the grp94 gene that codes for the 94-kD stress protein in the endoplasmic reticulum DNA Cell Biol. 1995 May; 14(5):373-84. . View in PubMed

Generation of a mammalian cell line deficient in glucose-regulated protein stress induction through targeted ribozyme driven by a stress-inducible promoter J Biol Chem. 1995 Apr 21; 270(16):9526-34. . View in PubMed

Identification of a 68 kDa protein species as a specific DNA-binding component of the H3abp complex interacting with the histone H32 G1/S regulatory domain. Nucleic Acids Res. 1995 Feb 11; 23(3):475-84. . View in PubMed

Constitutive expression of a microinjected glucose-regulated protein (grp78) fusion gene during early Xenopus laevis development Differentiation. 1994 Sep; 57(3):171-7. . View in PubMed

Erp61 is GRP58, a stress-inducible luminal endoplasmic reticulum protein, but is devoid of phosphatidylinositide-specific phospholipase C activity Arch Biochem Biophys. 1994 Feb 01; 308(2):454-60. . View in PubMed

A human HMG2 cDNA with a novel 3'-untranslated region Nucleic Acids Res. 1992 Dec 11; 20(23):6413. . View in PubMed

Establishment of a Chinese hamster ovary cell line that expresses grp78 antisense transcripts and suppresses A23187 induction of both GRP78 and GRP94 J Cell Physiol. 1992 Dec; 153(3):575-82. . View in PubMed

Identification of a 10-base pair protein binding site in the promoter of the hamster H32 gene required for the S phase dependent increase in transcription and its interaction with a Jun-like nuclear factor. Cell Growth Differ. 1992 Dec; 3(12):919-28. . View in PubMed

Brefeldin A as a regulator of grp78 gene expression in mammalian cells J Biol Chem. 1992 Apr 05; 267(10):7128-33. . View in PubMed

Identification of a protein-binding site in the promoter of the human thymidine kinase gene required for the G1-S-regulated transcription J Biol Chem. 1992 Feb 05; 267(4):2723-7. . View in PubMed

Comparison of the genomic organizations of the rat grp78 and hsc73 gene and their evolutionary implications DNA Seq. 1992; 3(1):41-8. . View in PubMed

Analysis of the expression of a glucose-regulated protein (GRP78) promoter/CAT fusion gene during early Xenopus laevis development Differentiation. 1992 Jan; 49(1):1-6. . View in PubMed

Glucose regulated protein induction and cellular resistance to oxidative stress mediated by porphyrin photosensitization Cancer Res. 1991 Dec 15; 51(24):6574-9. . View in PubMed

A binding site for the cyclic adenosine 3',5'-monophosphate-response element-binding protein as a regulatory element in the grp78 promoter Mol Endocrinol. 1991 Dec; 5(12):1862-72. . View in PubMed

Common sets of nuclear factors binding to the conserved promoter sequence motif of two coordinately regulated ER protein genes, GRP78 and GRP94 Nucleic Acids Res. 1991 Oct 11; 19(19):5425-31. . View in PubMed

Competitive inhibition of a set of endoplasmic reticulum protein genes (GRP78, GRP94, and ERp72) retards cell growth and lowers viability after ionophore treatment Mol Cell Biol. 1991 Jul; 11(7):3446-53. . View in PubMed

Identification of a 70-base-pair cell cycle regulatory unit within the promoter of the human thymidine kinase gene and its interaction with cellular factors Mol Cell Biol. 1991 Apr; 11(4):2296-302. . View in PubMed

Expression of the glucose-regulated proteins (GRP94 and GRP78) in differentiated and undifferentiated mouse embryonic cells and the use of the GRP78 promoter as an expression system in embryonic cells Differentiation. 1990 Feb; 42(3):153-9. . View in PubMed

Enhanced transcription of the 78,000-dalton glucose-regulated protein (GRP78) gene and association of GRP78 with immunoglobulin light chains in a nonsecreting B-cell myeloma line (NS-1) Mol Cell Biol. 1989 May; 9(5):2233-8. . View in PubMed

Glucose-regulated protein (GRP94 and GRP78) genes share common regulatory domains and are coordinately regulated by common trans-acting factors Mol Cell Biol. 1989 May; 9(5):2153-62. . View in PubMed

Cooperative interactions between the GRP78 enhancer and promoter elements in hamster fibroblasts Gene. 1989 Apr 15; 77(1):123-31. . View in PubMed

Cell cycle regulation of H2b histone octamer DNA-binding activity in Chinese hamster lung fibroblasts Mol Cell Biol. 1989 Feb; 9(2):869-73. . View in PubMed

Human gene encoding the 78,000-dalton glucose-regulated protein and its pseudogene: structure, conservation, and regulation DNA. 1988 May; 7(4):275-86. . View in PubMed

Depletion of intracellular calcium stores by calcium ionophore A23187 induces the genes for glucose-regulated proteins in hamster fibroblasts J Biol Chem. 1987 Sep 15; 262(26):12801-5. . View in PubMed

Cell-cycle regulatory sequences in a hamster histone promoter and their interactions with cellular factors Nature. 1987 Aug 27-Sep 2; 328(6133):823-7. . View in PubMed

Coordinated regulation of a set of genes by glucose and calcium ionophores in mammalian cells 1987; 12:20-23. . View in PubMed

Enhanced synthesis of the glucose/calcium-regulated proteins in a hamster cell mutant deficient in transfer of oligosaccharide core to polypeptides J Cell Physiol. 1986 Dec; 129(3):277-82. . View in PubMed

Calcium ionophore A23187 as a regulator of gene expression in mammalian cells J Cell Biol. 1986 Dec; 103(6 Pt 1):2145-52. . View in PubMed

Effect of E1A and E1B viral proteins on the expression of a calcium ionophore-inducible gene and its promoter Nucleic Acids Res. 1986 Jun 25; 14(12):4911-21. . View in PubMed

A calcium ionophore-inducible cellular promoter is highly active and has enhancerlike properties Mol Cell Biol. 1986 Apr; 6(4):1235-43. . View in PubMed

Calcium ionophore A23187 induces expression of glucose-regulated genes and their heterologous fusion genes Mol Cell Biol. 1985 Jun; 5(6):1212-9. . View in PubMed

Biochemical characterization of the 94- and 78-kilodalton glucose-regulated proteins in hamster fibroblasts J Biol Chem. 1984 Apr 10; 259(7):4616-21. . View in PubMed

Characterization of a cell cycle mutant derived from hamster fibroblast: reversion analysis J Cell Biol. 1982 Mar; 92(3):629-33. . View in PubMed

Coupling of histone and DNA synthesis in the somatic cell cycle Science. 1982 Jan 01; 215(4528):79-81. . View in PubMed

Highly conserved glucose-regulated protein in hamster and chicken cells: preliminary characterization of its cDNA clone Proc Natl Acad Sci U S A. 1981 Aug; 78(8):4922-5. . View in PubMed

Four sizes of transcript produced by a single sea urchin gene expressed in early embryos Proc Natl Acad Sci U S A. 1980 Jun; 77(6):3259-63. . View in PubMed

Developmental expression of two cloned sequences coding for rare sea urchin embryo messages Dev Biol. 1980 May; 76(2):322-40. . View in PubMed

Clones of individual repetitive sequences from sea urchin DNA constructed with synthetic Eco RI sites Science. 1977 Apr 08; 196(4286):197-200. . View in PubMed

A continuous electroelution method for the recovery of DNA restriction enzyme fragments Anal Biochem. 1974 Aug; 60(2):640-4. . View in PubMed

A cleavage map of bacteriophage phiX174 genome Proc Natl Acad Sci U S A. 1974 Jul; 71(7):2882-6. . View in PubMed

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