Prof SHI, Jue Jade, 史珏博士

My main research interest is to develop new and more effective cancer therapeutics and treatment strategies by understanding the quantitative mechanisms underlying variation in anticancer drug response in distinct cancer types as well as immune-cancer interactions that modulate various aspects of oncogenesis, metastasis and treatment response. My lab combines quantitative single-cell imaging, ensemble profiling and computational modeling of cellular pathway/network dynamics to uncover novel drug targets, new drug candidates, new immuno-oncology therapeutics and improved combinatorial strategies for cancer treatment. More broadly speaking, my lab aims to answer the fundamental question of how dynamics of signaling molecules and their associated networks/pathways control differential cellular response to specific environmental signals and stress stimuli, and apply the acquired mechanistic understanding to guide development of more effective cancer treatment.

Examples of current research projects include, but not limited to, the following:
 

1. Dynamics of anticancer drug response using novel 3D cancer organoid and spheroid models;

2. Cytototoxic dynamics of Natural killer cells against distinct cancer targets;

3. Development of new immuno-oncology drug and drug target through profiling immunomodulating traditional Chinese medicine.

1. Liu B, Zhu Y, Yang Z, Yan HHN, Leung S, Shi J*. (2024) Deep Learning-Based 3D Single-Cell Imaging Analysis Pipeline Enables Quantification of Cell-Cell Interaction Dynamics in the Tumor Microenvironment. Cancer Research, 84(4):517-526.
2. Cheng A, Xu T, You W, Wang T, Zhang D, Guo H, Zhang H, Pan X, Wang Y, Liu L, Zhang K, Shi J, Yao X, Guo J, Yang Z. (2023) A mitotic NADPH upsurge promotes chromosome segregation and tumour progression in aneuploid cancer cells. Nature Metabolism, 5(7): 1141-1158.
3. Zhu Y, Shi J*. (2023) Cytotoxic and chemotactic dynamics of NK cells quantified by live-cell imaging. Methods Cell Biol. 173: 49-64.
4. Xie J, Zhang L, Liu B, Liang X, Shi J*. (2022) Single-cell analysis of p53 transitional dynamics unravels stimulus- and cell type-dependent signaling output motifs. BMC Biology, 20(1):85.
5. To SKY, Tang MKS, Tong Y, Zhang J, Chan KKL, Ip PPC, Shi J*, Wong AST*. (2022) A Selective β-Catenin-Metadherin/CEACAM1-CCL3 Axis Mediates Metastatic Heterogeneity upon Tumor-Macrophage Interaction. Advanced Science, e2103230.
6. Shi J*, Weng JH, Mitchison TJ*. (2021) Immunomodulatory drug discovery from herbal medicines: insights from organ-specific activity and xenobiotic defences. eLife, 10: e73673.
7. Zhu Y, Xie J, Shi J*. (2021) Rac1/ROCK-driven membrane dynamics promote natural killer cell cytotoxicity via granzyme-induced necroptosis. BMC Biology, 19(1):140.
8. Yang R, Huang B, Zhu Y, Li Y, Liu F, Shi J*. (2018) Cell type-dependent bimodal p53 activation engenders a dynamic mechanism of chemoresistance. Science Advances, 4(12): eaat5077.
9. Choi M+, Shi J+, Zhu Y, Yang R, Cho K. (2017) Network dynamics-based stratification of cancer panel for systemic prediction of anticancer drug response. Nature Communications, 8(1), 1940. (+: co-first author)
10. Zhu Y, Huang B, Shi J*. (2016) Fas ligand and lytic granule differentially control cytotoxic dynamics of Natural Killer cell against cancer target. Oncotarget. 7(30):47163-72.
11. Zhu Y, Zhou Y, Shi J*. (2014) Post-slippage multinucleation renders cytotoxic variation in anti-mitotic drugs that target the microtubules or mitotic spindle. Cell Cycle. 13(11):1756-64.
12. Chen X, Chen J, Gan S, Guan H, Zhou Y, Ouyang Q, Shi J*. (2013) DNA damage strength modulates a bimodal switch of p53 dynamics for cell fate control. BMC Biology, 11(1): 73.
13. Shi J*, Zhou Y, Huang HC, Mitchison TJ. (2011) Navitoclax (ABT-263) accelerates apoptosis during drug-induced mitotic arrest by antagonizing Bcl-xL. Cancer Research. 71(13): 4518-26.
14. Huang HC, Shi J, Orth JD, Mitchison TJ. (2009) Evidence that mitotic exit is a better cancer therapeutic target than spindle assembly. Cancer Cell, 16(4): 347-58.
15. Shi J*, Orth JD, Mitchison T. (2008) Cell type variation in responses to antimitotic drugs that target microtubules and kinesin-5. Cancer Research, 68(9): 3269-76.
16. Shi J, Dertouzos J, Gafni A, Steel D and Palfey BA. (2006) Single molecule kinetics reveals new signatures of half-sites reactivity in dihydroorotate dehydrogenase A catalysis. Proc Natl Acad Sci USA. 103(15): 5775-80.  
17. Shi J, Palfey BA, Dertouzos J, Jensen KF, Gafni A and Steel D. (2004) Multiple states of the Tyr318Leu mutant of dihydroorotate dehydrogenase revealed by single-molecule kinetics. J. Am. Chem. Soc. 126(22): 6914-6922.