Keck School Faculty

Amy Shiu Lee

Amy Shiu Lee

Professor of Biochemistry & Molecular Medicine
Judy and Larry Freeman Chair in Basic Science Cancer Research
NOR 5306, 5310, 5312, 5314, 5338, 1441 Eastlake Avenue Health Sciences Campus Los Angeles


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

Hydra-Elastin-like Polypeptides Increase Rapamycin Potency When Targeting Cell Surface GRP78 Biomacromolecules. 2022 08 08; 23(8):3116-3129. . View in PubMed

ER residential chaperone GRP78 unconventionally relocalizes to the cell surface via endosomal transport Cell Mol Life Sci. 2021 Jun; 78(12):5179-5195. . View in PubMed

Suppression of ER-stress induction of GRP78 as an anti-neoplastic mechanism of the cardiac glycoside Lanatoside C in pancreatic cancer: Lanatoside C suppresses GRP78 stress induction Neoplasia. 2021 12; 23(12):1213-1226. . View in PubMed

Endoplasmic reticulum chaperone GRP78/BiP is critical for mutant Kras-driven lung tumorigenesis Oncogene. 2021 05; 40(20):3624-3632. . View in PubMed

The Hydroxyquinoline Analogue YUM70 Inhibits GRP78 to Induce ER Stress-Mediated Apoptosis in Pancreatic Cancer Cancer Res. 2021 04 01; 81(7):1883-1895. . View in PubMed

The chaperone GRP78 is a host auxiliary factor for SARS-CoV-2 and GRP78 depleting antibody blocks viral entry and infection J Biol Chem. 2021 Jan-Jun; 296:100759. . View in PubMed

Insulin-like growth factor 1-receptor signaling stimulates GRP78 expression through the PI3K/AKT/mTOR/ATF4 axis Cell Signal. 2020 11; 75:109736. . View in PubMed

The stress-inducible molecular chaperone GRP78 as potential therapeutic target for coronavirus infection J Infect. 2020 09; 81(3):452-482. . View in PubMed

Grp78 Loss in Epithelial Progenitors Reveals an Age-linked Role for Endoplasmic Reticulum Stress in Pulmonary Fibrosis Am J Respir Crit Care Med. 2020 01 15; 201(2):198-211. . View in PubMed

GRP78 regulates CD44v membrane homeostasis and cell spreading in tamoxifen-resistant breast cancer Life Sci Alliance. 2019 08; 2(4). . View in PubMed

The COOH-Terminal Proline-Rich Region of GRP78 Is a Key Regulator of Its Cell Surface Expression and Viability of Tamoxifen-Resistant Breast Cancer Cells Neoplasia. 2019 08; 21(8):837-848. . View in PubMed

Suppression of stress induction of the 78-kilodalton glucose regulated protein (GRP78) in cancer by IT-139, an anti-tumor ruthenium small molecule inhibitor Oncotarget. 2018 Jul 03; 9(51):29698-29714. . View in PubMed

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

Heterozygosity of Chaperone Grp78 Reduces Intestinal Stem Cell Regeneration Potential and Protects against Adenoma Formation Cancer Res. 2018 11 01; 78(21):6098-6106. . View in PubMed

Proc Natl Acad Sci U S A. 2018 05 01; 115(18):E4245-E4254. . View in PubMed

The Endoplasmic Reticulum Chaperone GRP78/BiP Modulates Prion Propagation in vitro and in vivo Sci Rep. 2017 03 23; 7:44723. . View in PubMed

Induction of endoplasmic reticulum stress by deletion of Grp78 depletes Apc mutant intestinal epithelial stem cells Oncogene. 2017 06 15; 36(24):3397-3405. . View in PubMed

New role of endoplasmic reticulum chaperones in regulating metaplasia during tumorigenesis Mol Cell Oncol. 2017; 4(6):e1345350. . 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

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

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

The 78-kD Glucose-Regulated Protein Regulates Endoplasmic Reticulum Homeostasis and Distal Epithelial Cell Survival during Lung Development Am J Respir Cell Mol Biol. 2016 07; 55(1):135-49. . 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

Targeting the glucose-regulated protein-78 abrogates Pten-null driven AKT activation and endometrioid tumorigenesis Oncogene. 2015 Oct; 34(43):5418-26. . View in PubMed

Role of the unfolded protein response, GRP78 and GRP94 in organ homeostasis J Cell Physiol. 2015 Jul; 230(7):1413-20. . View in PubMed

Reply: To PMID 24027047 Hepatology. 2015 May; 61(5):1767-8. . 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

Targeted deletion of ER chaperone GRP94 in the liver results in injury, repopulation of GRP94-positive hepatocytes, and spontaneous hepatocellular carcinoma development in aged mice Neoplasia. 2014 Aug; 16(8):617-26. . 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

Liver-specific knockout of GRP94 in mice disrupts cell adhesion, activates liver progenitor cells, and accelerates liver tumorigenesis Hepatology. 2014 Mar; 59(3):947-57. . View in PubMed

Monoclonal antibody against cell surface GRP78 as a novel agent in suppressing PI3K/AKT signaling, tumor growth, and metastasis Clin Cancer Res. 2013 Dec 15; 19(24):6802-11. . 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

miR-30d, miR-181a and miR-199a-5p cooperatively suppress the endoplasmic reticulum chaperone and signaling regulator GRP78 in cancer Oncogene. 2013 Sep 26; 32(39):4694-701. . 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

The endoplasmic reticulum stress marker, glucose-regulated protein-78 (GRP78) in visceral adipocytes predicts endometrial cancer progression and patient survival Gynecol Oncol. 2013 Mar; 128(3):552-9. . View in PubMed

The critical roles of endoplasmic reticulum chaperones and unfolded protein response in tumorigenesis and anticancer therapies Oncogene. 2013 Feb 14; 32(7):805-18. . 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

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

Inducible knockout of GRP78/BiP in the hematopoietic system suppresses Pten-null leukemogenesis and AKT oncogenic signaling Blood. 2012 Jan 19; 119(3):817-25. . 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):2431-2439. . View in PubMed

Soy food supplementation, dietary fat reduction and peripheral blood gene expression in postmenopausal women--a randomized, controlled trial Mol Nutr Food Res. 2011 Sep; 55 Suppl 2:S264-77. . View in PubMed

Inositol 1,4,5-trisphosphate receptor 1 mutation perturbs glucose homeostasis and enhances susceptibility to diet-induced diabetes J Endocrinol. 2011 Aug; 210(2):209-17. . View in PubMed

Novel mechanism of anti-apoptotic function of 78-kDa glucose-regulated protein (GRP78): endocrine resistance factor in breast cancer, through release of B-cell lymphoma 2 (BCL-2) from BCL-2-interacting killer (BIK) J Biol Chem. 2011 Jul 22; 286(29):25687-96. . View in PubMed

Liver-specific loss of glucose-regulated protein 78 perturbs the unfolded protein response and exacerbates a spectrum of liver diseases in mice Hepatology. 2011 Jul; 54(1):229-39. . View in PubMed

Impaired eyeblink conditioning in 78 kDa-glucose regulated protein (GRP78)/immunoglobulin binding protein (BiP) conditional knockout mice Behav Neurosci. 2011 Jun; 125(3):404-11. . 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

The critical role of GRP78 in physiologic and pathologic stress Curr Opin Cell Biol. 2011 Apr; 23(2):150-6. . 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

Overexpressing GRP78 influences Ca2+ handling and function of mitochondria in astrocytes after ischemia-like stress Mitochondrion. 2011 Mar; 11(2):279-86. . 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

The endoplasmic reticulum chaperone protein GRP94 is required for maintaining hematopoietic stem cell interactions with the adult bone marrow niche PLoS One. 2011; 6(5):e20364. . 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

The endothelial cell receptor GRP78 is required for mucormycosis pathogenesis in diabetic mice J Clin Invest. 2010 Jun; 120(6):1914-24. . View in PubMed

Targeted mutation of the mouse Grp94 gene disrupts development and perturbs endoplasmic reticulum stress signaling PLoS One. 2010 May 26; 5(5):e10852. . 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):15065-15075. . 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

The Par-4-GRP78 TRAIL, more twists and turns Cancer Biol Ther. 2009 Nov; 8(22):2103-5. . View in PubMed

Role of the unfolded protein response regulator GRP78/BiP in development, cancer, and neurological disorders Antioxid Redox Signal. 2009 Sep; 11(9):2307-16. . View in PubMed

Regulation of PERK signaling and leukemic cell survival by a novel cytosolic isoform of the UPR regulator GRP78/BiP PLoS One. 2009 Aug 31; 4(8):e6868. . View in PubMed

Transcriptional induction of GRP78/BiP by histone deacetylase inhibitors and resistance to histone deacetylase inhibitor-induced apoptosis Mol Cancer Ther. 2009 May; 8(5):1086-94. . View in PubMed

Pten null prostate tumorigenesis and AKT activation are blocked by targeted knockout of ER chaperone GRP78/BiP in prostate epithelium Proc Natl Acad Sci U S A. 2008 Dec 09; 105(49):19444-9. . 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

The unfolded protein response regulator GRP78/BiP is required for endoplasmic reticulum integrity and stress-induced autophagy in mammalian cells Cell Death Differ. 2008 Sep; 15(9):1460-71. . View in PubMed

Stress chaperone GRP78/BiP confers chemoresistance to tumor-associated endothelial cells Mol Cancer Res. 2008 Aug; 6(8):1268-75. . 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

Pyrvinium targets the unfolded protein response to hypoglycemia and its anti-tumor activity is enhanced by combination therapy PLoS One. 2008; 3(12):e3951. . View in PubMed

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. . 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

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

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

The effect of dexamethasone on defective nephrin transport caused by ER stress: a potential mechanism for the therapeutic action of glucocorticoids in the acquired glomerular diseases Kidney Int. 2006 Apr; 69(8):1350-9. . View in PubMed

In vivo regulation of Grp78/BiP transcription in the embryonic heart: role of the endoplasmic reticulum stress response element and GATA-4 J Biol Chem. 2006 Mar 31; 281(13):8877-87. . 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

Stress induction of GRP78/BiP and its role in cancer Curr Mol Med. 2006 Feb; 6(1):45-54. . View in PubMed

Vascular targeting and antiangiogenesis agents induce drug resistance effector GRP78 within the tumor microenvironment Cancer Res. 2005 Jul 01; 65(13):5785-91. . 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

Transcriptional regulation of the Grp78 promoter by endoplasmic reticulum stress: role of TFII-I and its tyrosine phosphorylation J Biol Chem. 2005 Apr 29; 280(17):16821-8. . View in PubMed

The ER chaperone and signaling regulator GRP78/BiP as a monitor of endoplasmic reticulum stress Methods. 2005 Apr; 35(4):373-81. . View in PubMed

Transgenic mouse model for monitoring endoplasmic reticulum stress in vivo Nat Med. 2004 Oct; 10(10):1013-4; author reply 1014. . 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

Spontaneous and controllable activation of suicide gene expression driven by the stress-inducible grp78 promoter resulting in eradication of sizable human tumors Hum Gene Ther. 2004 Jun; 15(6):553-61. . View in PubMed

Underglycosylation of ATF6 as a novel sensing mechanism for activation of the unfolded protein response J Biol Chem. 2004 Mar 19; 279(12):11354-63. . View in PubMed

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

Induction of Grp78/BiP by translational block: activation of the Grp78 promoter by ATF4 through and upstream ATF/CRE site independent of the endoplasmic reticulum stress elements J Biol Chem. 2003 Sep 26; 278(39):37375-85. . 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

Requirement of the p38 mitogen-activated protein kinase signalling pathway for the induction of the 78 kDa glucose-regulated protein/immunoglobulin heavy-chain binding protein by azetidine stress: activating transcription factor 6 as a target for stress-induced phosphorylation Biochem J. 2002 Sep 15; 366(Pt 3):787-95. . 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

The glucose-regulated proteins: stress induction and clinical applications Trends Biochem Sci. 2001 Aug; 26(8):504-10. . View in PubMed

Identification of TFII-I as the endoplasmic reticulum stress response element binding factor ERSF: its autoregulation by stress and interaction with ATF6 Mol Cell Biol. 2001 May; 21(9):3220-33. . View in PubMed

YY1 as a regulator of replication-dependent hamster histone H32 promoter and an interactive partner of AP-2. J Biol Chem. 2001 Jan 05; 276(1):28-34. . View in PubMed

Upregulation of BiP and CHOP by the unfolded-protein response is independent of presenilin expression Nat Cell Biol. 2000 Dec; 2(12):863-70. . 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

The endoplasmic reticulum chaperone glycoprotein GRP94 with Ca(2+)-binding and antiapoptotic properties is a novel proteolytic target of calpain during etoposide-induced apoptosis J Biol Chem. 1999 Oct 01; 274(40):28476-83. . View in PubMed

Use of the glucose starvation-inducible glucose-regulated protein 78 promoter in suicide gene therapy of murine fibrosarcoma Cancer Res. 1999 Jul 01; 59(13):3100-6. . View in PubMed

The mammalian endoplasmic reticulum stress response element consists of an evolutionarily conserved tripartite structure and interacts with a novel stress-inducible complex Nucleic Acids Res. 1999 Mar 15; 27(6):1437-43. . 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

Identification of AP-2 as an interactive target of Rb and a regulator of the G1/S control element of the hamster histone H32 promoter. Nucleic Acids Res. 1998 Nov 01; 26(21):4837-45. . 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

Mechanism for the suppression of the mammalian stress response by genistein, an anticancer phytoestrogen from soy J Natl Cancer Inst. 1998 Mar 04; 90(5):381-8. . View in PubMed

Positive and negative regulation of the human thymidine kinase promoter mediated by CCAAT binding transcription factors NF-Y/CBF, dbpA, and CDP/cut Cell Growth Differ. 1997 Dec; 8(12):1329-38. . 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

Induction of the mammalian GRP78/BiP gene by Ca2+ depletion and formation of aberrant proteins: activation of the conserved stress-inducible grp core promoter element by the human nuclear factor YY1 Mol Cell Biol. 1997 Jan; 17(1):54-60. . View in PubMed

Suppression of grp78 core promoter element-mediated stress induction by the dbpA and dbpB (YB-1) cold shock domain proteins Mol Cell Biol. 1997 Jan; 17(1):61-8. . 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

Induction of glucose-regulated protein (glucose-regulated protein 78/BiP and glucose-regulated protein 94) and heat shock protein 70 transcripts in the immature rat brain following status epilepticus Neuroscience. 1996 Nov; 75(1):209-19. . View in PubMed

Inhibition of tumor progression by suppression of stress protein GRP78/BiP induction in fibrosarcoma B/C10ME Proc Natl Acad Sci U S A. 1996 Jul 23; 93(15):7690-4. . 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

Use of the stress-inducible grp78/BiP promoter in targeting high level gene expression in fibrosarcoma in vivo Cancer Res. 1995 Apr 15; 55(8):1660-3. . View in PubMed

Transduction of calcium stress through interaction of the human transcription factor CBF with the proximal CCAAT regulatory element of the grp78/BiP promoter Mol Cell Biol. 1995 Apr; 15(4):2263-74. . 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

Requirement of tyrosine- and serine/threonine kinases in the transcriptional activation of the mammalian grp78/BiP promoter by thapsigargin J Biol Chem. 1995 Jan 06; 270(1):494-502. . 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

Stress induction of the mammalian GRP78/BiP protein gene: in vivo genomic footprinting and identification of p70CORE from human nuclear extract as a DNA-binding component specific to the stress regulatory element Mol Cell Biol. 1994 Aug; 14(8):5533-46. . View in PubMed

Localization of the gene encoding human BiP/GRP78, the endoplasmic reticulum cognate of the HSP70 family, to chromosome 9q34 Genomics. 1994 Mar 15; 20(2):281-4. . 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

Increased cytotoxicity of chronic hypoxic cells by molecular inhibition of GRP78 induction Int J Radiat Oncol Biol Phys. 1994 Feb 01; 28(3):661-6. . View in PubMed

The glucose-regulated proteins (GRP78 and GRP94): functions, gene regulation, and applications Crit Rev Eukaryot Gene Expr. 1994; 4(1):1-18. . View in PubMed

Suppression of stress protein GRP78 induction in tumor B/C10ME eliminates resistance to cell mediated cytotoxicity Cancer Res. 1993 Dec 15; 53(24):6001-5. . View in PubMed

Transactivation of the grp78 promoter by Ca2+ depletionA comparative analysis with A23187 and the endoplasmic reticulum Ca(2+)-ATPase inhibitor thapsigargin. J Biol Chem. 1993 Jun 05; 268(16):12003-9. . View in PubMed

Temporal regulation of cyclin A-p107 and p33cdk2 complexes binding to a human thymidine kinase promoter element important for G1-S phase transcriptional regulation Proc Natl Acad Sci U S A. 1993 Apr 15; 90(8):3554-8. . 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

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

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

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

Mammalian stress response: induction of the glucose-regulated protein family Curr Opin Cell Biol. 1992 Apr; 4(2):267-73. . 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

Transactivation of the grp78 promoter by malfolded proteins, glycosylation block, and calcium ionophore is mediated through a proximal region containing a CCAAT motif which interacts with CTF/NF-I Mol Cell Biol. 1991 Nov; 11(11):5612-23. . 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

Proteolytic conversion of hepatitis B virus e antigen precursor to end product occurs in a postendoplasmic reticulum compartment J Virol. 1991 Sep; 65(9):5080-3. . 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

Temporal events regulating the early phases of the mammalian cell cycle Curr Opin Cell Biol. 1991 Apr; 3(2):261-8. . 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

The rat 78,000 dalton glucose-regulated protein (GRP78) as a precursor for the rat steroidogenesis-activator polypeptide (SAP): the SAP coding sequence is homologous with the terminal end of GRP78 Mol Endocrinol. 1989 Dec; 3(12):1944-52. . View in PubMed

Transcriptional regulation of the gene encoding the 78-kD glucose-regulated protein GRP78 in mouse sertoli cells: binding of specific factor(s) to the GRP78 promoter DNA. 1989 Jun; 8(5):301-10. . 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

Interaction of cellular factors related to the Jun oncoprotein with the promoter of a replication-dependent hamster histone H32 gene. Proc Natl Acad Sci U S A. 1989 Jan; 86(2):491-5. . View in PubMed

Identity of the immunoglobulin heavy-chain-binding protein with the 78,000-dalton glucose-regulated protein and the role of posttranslational modifications in its binding function Mol Cell Biol. 1988 Oct; 8(10):4250-6. . View in PubMed

Identification of highly conserved regulatory domains and protein-binding sites in the promoters of the rat and human genes encoding the stress-inducible 78-kilodalton glucose-regulated protein Mol Cell Biol. 1988 Oct; 8(10):4579-84. . View in PubMed

The organization of the rat GRP78 gene and A23187-induced expression of fusion gene products targeted intracellularly Exp Cell Res. 1988 Sep; 178(1):84-92. . View in PubMed

Sequences contained within the promoter of the human thymidine kinase gene can direct cell-cycle regulation of heterologous fusion genes Proc Natl Acad Sci U S A. 1988 Aug; 85(16):5894-8. . 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

Increased expression of the glucose-regulated gene encoding the Mr 78,000 glucose-regulated protein in chemically and radiation-transformed C3H 10T1/2 mouse embryo cells Cancer Res. 1987 Dec 01; 47(23):6220-4. . View in PubMed

Regulation of the glucose-regulated protein genes by beta-mercaptoethanol requires de novo protein synthesis and correlates with inhibition of protein glycosylation J Cell Physiol. 1987 Dec; 133(3):553-9. . 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

Transcriptional activation of the glucose-regulated protein genes and their heterologous fusion genes by beta-mercaptoethanol Mol Cell Biol. 1987 Aug; 7(8):2974-6. . View in PubMed

Rat gene encoding the 78-kDa glucose-regulated protein GRP78: its regulatory sequences and the effect of protein glycosylation on its expression Proc Natl Acad Sci U S A. 1987 Feb; 84(3):680-4. . View in PubMed

The nucleotide sequence encoding the hamster 78-kDa glucose-regulated protein (GRP78) and its conservation between hamster and rat Gene. 1987; 55(1):147-52. . 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

The effect of extracellular Ca2+ and temperature on the induction of the heat-shock and glucose-regulated proteins in hamster fibroblasts Biochem Biophys Res Commun. 1986 Nov 14; 140(3):881-7. . 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

Methylation analysis of a plasmid containing a mammalian cell cycle regulatory sequence after transient transfection into the host cell Biochem Biophys Res Commun. 1986 Mar 28; 135(3):942-9. . View in PubMed

Isolation of a mammalian sequence capable of conferring cell cycle regulation to a heterologous gene Science. 1985 Nov 29; 230(4729):1061-3. . 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

Use of a cell cycle mutant to delineate the critical period for the control of histone mRNA levels in the mammalian cell cycle Mol Cell Biol. 1984 Nov; 4(11):2364-9. . View in PubMed

Regulation of a hybrid gene by glucose and temperature in hamster fibroblasts Science. 1984 Oct 12; 226(4671):187-90. . 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

Induction of two genes by glucose starvation in hamster fibroblasts Proc Natl Acad Sci U S A. 1984 Feb; 81(4):988-92. . View in PubMed

Polymerization of vector DNA after transfection into hamster fibroblast cells Biochem Biophys Res Commun. 1983 Jan 27; 110(2):593-601. . View in PubMed

Transcriptional regulation of two genes specifically induced by glucose starvation in a hamster mutant fibroblast cell line J Biol Chem. 1983 Jan 10; 258(1):597-603. . 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

The accumulation of three specific proteins related to glucose-regulated proteins in a temperature-sensitive hamster mutant cell line K12 J Cell Physiol. 1981 Jan; 106(1):119-25. . 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

Interspersion of short repetitive sequences studied in cloned sea urchin DNA fragments Science. 1977 Apr 08; 196(4286):189-2. . 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

Location of the 5-methylcytosine group on the bacteriophage phi X174 genome J Virol. 1974 Oct; 14(4):872-7. . 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

Production of specific fragments of phi X174 replicative form DNA by a restriction enzyme from Haemophilus parainfluenzae, endonuclease HP J Virol. 1973 Apr; 11(4):596-9. . View in PubMed

Dr. Amy Lee is Freeman Chair of Basic Science 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).
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