Amy Shiu Lee
Amy S. Lee is a Chinese-born American biochemist and cancer biologist. She has served as Professor of Biochemistry and Molecular Medicine at the Keck School of Medicine of the University of Southern California (USC) from 1979 to 2025. Lee is best known for her pioneering research on endoplasmic reticulum (ER) stress and the discovery, regulation, and functions of the ER chaperone glucose-regulated protein 78 (GRP78), also known as BiP.[1][2] Her work has been highly influential in elucidating the role of ER stress responses in development, cancer progression, therapeutic resistance, and viral infection. She served as Associate Director for Basic Research at the USC Norris Comprehensive Cancer Center from 1996 to 2019 and held the Judy and Larry Freeman Chair in Basic Science in Cancer Research.[3] She has been Professor Emeritus at USC since 2026.
Early life and education
Lee was born in Guangzhou, China, and grew up in Hong Kong. She completed her secondary education at Maryknoll Convent School and Diocesan Girls’ School. She earned a Bachelor of Arts degree in Bacteriology and Immunology from the University of California, Berkeley, graduating as valedictorian in 1970. She subsequently attended the California Institute of Technology, where she received a Master of Science degree in 1972 and a Doctor of Philosophy degree in 1975.
Academic career
Following postdoctoral training and service as a senior research associate at the California Institute of Technology, Lee joined the Department of Biochemistry at the Keck School of Medicine of USC in 1979 as an assistant professor. There, she established a research program focused on mammalian stress responses and molecular chaperones[4]. Over the course of her career, she held multiple leadership roles at the USC Norris Comprehensive Cancer Center, including Director of the Gene Regulation Program (1987–1997), Associate Director for Basic Research (1996–2019), and Associate Director for Shared Resources (2020–2021).
Lee has also been recognized for her sustained commitment to mentoring graduate students, postdoctoral fellows, and junior faculty at USC, contributing significantly to the training mission of the USC Keck School of Medicine.
Research contributions
ER stress and glucose-regulated proteins
Lee’s laboratory is the first to clone and characterize the mammalian genes encoding endoplasmic reticulum stress–inducible glucose-regulated proteins (GRPs). Her work helped define the transcriptional and post-transcriptional mechanisms governing GRP expression and established ER stress responses as central regulators of cellular homeostasis during development and disease[5].
GRP78 in cancer biology
A major focus of Lee’s research has been the ER chaperone GRP78. Her laboratory demonstrated that GRP78 plays a critical role in tumorigenesis, metastatic progression, and resistance to cancer therapies[6][7]. She also reported that under conditions of cellular stress, GRP78 can relocalize from the ER to other cellular compartments, including the cell surface, where it functions as a co-receptor in oncogenic signaling pathways[8]. Additionally, her group provided evidence that stress conditions can promote nuclear localization of GRP78, where it influences gene regulatory programs associated with cell migration and invasion[9][10][11]. These findings challenged prevailing models of protein compartmentalization and expanded understanding of noncanonical chaperone functions in cancer[5].
GRP78 and viral infection
During the COVID-19 pandemic, Lee’s laboratory investigated the role of GRP78 in viral infection. Her group reported that cell surface–localized GRP78 functions as a host co-receptor for SARS-CoV-2 entry and that ER-localized GRP78 is required for efficient viral protein folding and production[12][13]. This work suggests that targeting GRP78 could have therapeutic potential against both cancer and viral pathogens that exploit ER stress pathways[14]
Honors and awards
· Departmental Citation, University of California, Berkeley, Department of Bacteriology and Immunology (1970)
· American Cancer Society Junior Faculty Research Award (1980)
· American Cancer Society Faculty Research Award (1983)
· National Cancer Institute MERIT Award (1988)
· Judy and Larry Freeman Chair in Basic Science in Cancer Research (1997)
· Fellow, American Association for the Advancement of Science (2006)
· USC Mellon Mentoring Award (2012)
· National Academy of Inventors Award (2017)
· USC Associates Award for Creativity in Research and Scholarship (2018)[15]
· Mark Brothers Award, Indiana University School of Medicine (2019)[16]
· Spirit of Budapest Pioneer Award, Cell Stress Society International (2019)
Legacy
Lee’s research has had a lasting impact on the fields of cell stress biology and cancer research. Her discoveries regarding GRP78 have shaped contemporary understanding of ER stress signaling and continue to inform therapeutic strategies targeting cancer progression, metastasis, resistance, and viral infection.
References
- ↑ https://profiles.sc-ctsi.org/amy.lee
- ↑ https://research.com/u/amy-s-lee
- ↑ https://uscnorriscancer.usc.edu/wp-content/uploads/2025/02/Jan.Feb-2025_Community-for-a-Cure_FINAL.pdf
- ↑ https://keck.usc.edu/news/faculty-spotlight-amy-s-lee/
- ↑ 5.0 5.1 Lee, Amy S. (2025-07-29). "Stress-induced translocation of the endoplasmic reticulum chaperone GRP78/BiP and its impact on human disease and therapy". Proceedings of the National Academy of Sciences. 122 (30): e2412246122. doi:10.1073/pnas.2412246122. PMC 12318151 Check
|pmc=value (help). PMID 40699920 Check|pmid=value (help). - ↑ Lee, Amy S. (2014-04). "Glucose-regulated proteins in cancer: molecular mechanisms and therapeutic potential". Nature Reviews Cancer. 14 (4): 263–276. doi:10.1038/nrc3701. ISSN 1474-1768. PMC 4158750. PMID 24658275. Check date values in:
|date=(help) - ↑ Dacuma, Mary (2017-05-24). "The Secret to Combating Pancreatic Cancer May Lie in Suppression of a Common Protein". Newsroom. Retrieved 2026-01-17.
- ↑ Tsai, Yuan-Li; Ha, Dat P.; Zhao, He; Carlos, Anthony J.; Wei, Shan; Pun, Tsam Kiu; Wu, Kaijin; Zandi, Ebrahim; Kelly, Kevin; Lee, Amy S. (2018-05). "Endoplasmic reticulum stress activates SRC, relocating chaperones to the cell surface where GRP78/CD109 blocks TGF-β signaling". Proceedings of the National Academy of Sciences. 115 (18): E4245–E4254. doi:10.1073/pnas.1714866115. PMC 5939063. PMID 29654145. Check date values in:
|date=(help) - ↑ Liu, Ze; Liu, Guanlin; Ha, Dat P.; Wang, Justin; Xiong, Min; Lee, Amy S. (2023-08). "ER chaperone GRP78/BiP translocates to the nucleus under stress and acts as a transcriptional regulator". Proceedings of the National Academy of Sciences. 120 (31): e2303448120. doi:10.1073/pnas.2303448120. PMC 10400976 Check
|pmc=value (help). PMID 37487081 Check|pmid=value (help). Check date values in:|date=(help) - ↑ Abrams, Zara (2023-07-24). "Study finds new, unexpected mechanism of cancer cell spread". Newsroom. Retrieved 2026-01-17.
- ↑ Floersh, Helen (2023-07-24). "Cancer metastasis may be driven by a protein on the move: study". www.fiercebiotech.com. Retrieved 2026-01-17.
- ↑ Carlos, Anthony J.; Ha, Dat P.; Yeh, Da-Wei; Krieken, Richard Van; Tseng, Chun-Chih; Zhang, Pu; Gill, Parkash; Machida, Keigo; Lee, Amy S. (2021-01-01). "The chaperone GRP78 is a host auxiliary factor for SARS-CoV-2 and GRP78 depleting antibody blocks viral entry and infection". Journal of Biological Chemistry. 296. doi:10.1016/j.jbc.2021.100759. ISSN 0021-9258. PMC 8102082 Check
|pmc=value (help). PMID 33965375 Check|pmid=value (help). - ↑ Relations, Keck School Media (2021-05-24). "KSOM study reveals potential new treatment target in the fight against COVID-19". Newsroom. Retrieved 2026-01-17.
- ↑ Floersh, Helen (2022-11-17). "How COVID-19 and cancer could be treated with the same drug". www.fiercebiotech.com. Retrieved 2026-01-17.
- ↑ Relations, Keck School Media (2018-04-26). "Amy Lee, Eddie Sheh among honorees at Academic Honors Convocation". Newsroom. Retrieved 2026-01-17.
- ↑ Relations, Keck School Media (2019-04-17). "Amy Lee, PhD, Honored For Contributions to Biomedical Science". Newsroom. Retrieved 2026-01-17.
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