Jieya Shao, Ph.D.

Assistant Professor
Internal Medicine
Oncology

Cancer Biology Program
Molecular Cell Biology Program
Molecular Genetics and Genomics Program
Biochemistry, Biophysics, and Structural Biology Program

  • 314-362-8695

  • 314-747-9310

  • 314-747-9320

  • 4515 McKinley Building, 3rd floor

  • shao.j@wustl.edu

  • www.shaolab.org

  • cancer, genome stability, targeted therapy, proteostasis, autophagy, DNA replication stress, DNA damage response, phosphorylation

  • Molecular mechanisms and therapeutic potential of novel cancer targets

Research Abstract:

As a curiosity-driven cancer biology lab, we are broadly interested in uncovering novel cancer targets with the overarching goal of improving patient outcome. Currently, we are focusing on dissecting the complex molecular mechanisms governing genome stability which plays an important role in cancer initiation, progression, and treatment response. Our studies center around two multi-functional proteins, the actin-binding protein Profilin-1 and the AAA+ ATPase p97/VCP. Both are essential proteins with well-known functions in the cytoplasm, but play important yet poorly understood roles in the nucleus. Our recently published and currently ongoing work link nuclear Profilin-1 and p97/VCP to fundamentally important cellular processes including transcription, DNA replication, and DNA damage repair. Our findings highlight the importance of subcellular localization and post-translational modification in the regulation of multi-functional proteins such as Profilin-1 and p97-VCP, and implicate new ways to target their cancer-specific “moonlighting” functions. We believe that mechanistic insights from such studies can reveal hidden “Achilles heels” of cancer cells, and guide the development of novel and personalized treatments.

Selected Publications:

1. Wang F, Vij K, Li L, Dodhiawala P, Lim KH, Shao J. Phospho-Ser784-VCP Drives Resistance of Pancreatic Ductal Adenocarcinoma to Genotoxic Chemotherapies and Predicts the Chemo-Sensitizing Effect of VCP Inhibitor. Cancers (Basel) 2021 Oct 11;13(20):5076.

2. Wang F, Zhu C, Cai S, Boudreau A, Kim S, Bissell MJ, Shao J. Ser71 phosphorylation inhibits actin-binding of profilin-1 and its apoptosis-sensitizing activity. Front Cell Dev Biol. 2021; 9:692269.

3. Zhu C*, Kim S*, Mooradian A, Wang F, Li Z, Holohan S, Collins P, Wang K, Guo Z, Hoog J, Ma CX, Oltz EM, Held JM, Shao J. Cancer-Associated Exportin-6 Upregulation Inhibits the Transcriptionally Repressive and Anticancer Effects of Nuclear Profilin-1. (*Equal Contribution) Cell Rep. 2021; 34(7):108749.

4. Shao J. Ser784 phosphorylation: a clinically relevant enhancer of VCP function in the DNA damage response. Mol Cell Oncol. 2020; 7(5):1796179.

5. Zhu C*, Rogers A*, Asleh K*, Won J, Gao D, Leung S, Li S, Vij KR, Zhu J, Held JM, You Z, Nielsen TO, Shao J. Phospho-Ser784-VCP Is Required for DNA Damage Response and Is Associated With Poor Prognosis of Chemotherapy-Treated Breast Cancer. (*Equal Contribution) Cell Rep. 2020; 31(10):107745.

6. Lei J*, Shao J*, Zhang J*, Iglesia M*, Chan CW, Cao J, Anurag M, Singh P, He X, Kosaka Y, Matsunuma R, Crowder R, Hoog J, Phommaly C, Goncalves R, Ramalho S, Peres RM, Punturi N, Schmidt C, Bartram A, Jou E, Devarakonda V, Holloway KR, Lai W, Hampton O, Rogers A, Tobias E, Parikh P, Davies SR, Li S, Ma CX, Suman V, Hunt K, Watson M, Hoadley KA, Thompson A, Chen X, Kavuri SM, Creighton CJ, Maher C, Perou C, Haricharan S, Ellis MJ. Functional annotation of ESR1 gene fusions in estrogen receptor positive breast cancer. (*Equal Contribution) Cell Rep. 2018; 24(6):1434-1444.

7. Diamond MI, Cai S, Boudreau A, Carey CJ Jr, Lyle N, Pappu RV, Swamidass SJ, Bissell M, Piwnica-Worms H, Shao J. (2015) Subcellular localization and Ser-137 phosphorylation regulate tumor-suppressive activity of profilin-1. Journal of Biological Chemistry, 290(14):9075-86. PubMed PMID: 25681442; PubMed Central PMCID: PMC4423694

8. Li S*, Shen D*, Shao J, Crowder R, Liu W, Prat A, He X, Liu S, Hoog J, Lu C, Ding L, Griffith OL, Miller C, Larson D, Fulton RS, Harrison M, Mooney T, McMichael JF, Luo J, Tao Y, Goncalves R, Schlosberg C, Hiken JF, Saied L, Sanchez C, Giuntoli T, Bumb C, Cooper C, Kitchens RT, Lin A, Phommaly C, Davies SR, Zhang J, Kavuri MS, McEachern D, Dong YY, Ma C, Pluard T, Naughton M, Bose R, Suresh R, McDowell R, Michel L, Aft R, Gillanders W, DeSchryver K, Wilson RK, Wang S, Mills GB, Gonzalez-Angulo A, Edwards JR, Maher C, Perou CM, Mardis ER, Ellis MJ. Endocrine-therapy-resistant ESR1 variants revealed by genomic characterization of breast-cancer-derived xenografts. (*Equal Contribution) Cell Rep. 2013;4(6):1116-1130.

Last Updated: 12/21/2021 12:30:47 PM

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