Shen Laboratory

Research Synopsis

The Clinical Challenge:
(1) Glioblastoma (GBM), the most aggressive adult brain cancer, claims more than 15,000 lives annually in the United States. Despite surgery, radiation, and chemotherapy, the median survival remains only about 15 months, with nearly universal recurrence.
(2) Diffuse midline glioma (DMG), one of the most lethal pediatric brain tumors, arises in critical midline structures where surgical resection is not feasible. Despite radiation therapy, the median survival remains less than one year, and recurrence is nearly universal.

Tumor Plasticity and Recurrence:
One important contributor to therapeutic failure in both GBM and DMG is the presence of cancer stem-like cells (CSCs), also known as tumor-initiating cells, which possess the capacity for self-renewal and differentiation. In these tumors, CSC states are dynamic rather than fixed; malignant cells can transition along a CSC to non-CSC continuum, and therapy-induced stress reshapes this balance, driving intratumoral heterogeneity, treatment resistance, and tumor recurrence.

Mission:
We are committed to defeating these CSCs and non-CSCs. Our approach integrates computational analysis with precision immunotherapy to revolutionize treatment outcomes.

Publications

Recent Publications

Xie Q, Wang B, Ma Q, Shen J (2026). A glioma stem cell-associated signature predicts survival across adult and pediatric high grade gliomas and reveals the FAM86B1/FAM86B2 axis. medRxiv. doi: https://doi.org/10.1101/2025.10.15.25338073.

Mast J, Cao B, Xie Q, Shen J (2025). Glioblastoma stem cells evade NK cell killing through downregulation of NKG2D ligands. Neuro-Oncology. Volume 27, Issue Supplement_5, Page v79. doi: 10.1080/17501911.2025.2568366.

Cao B, Xie Q, Li C, Mast J, Hamdouchi C, Grese T, Shen J (2025). SUV39H2 is a therapeutic vulnerability in glioblastoma stem cells enhanced by co-targeting SUV39H1. Epigenomics. doi: 10.1080/17501911.2025.2568366.

Cao B, Wheeler G, Mast J, Zhao Q, Shen J (2025). Combining microwave ablation with CAR-T cell therapy in tumor-bearing mouse models. Bio-Protocol. doi: 10.21769/BioProtoc.5470.

Zhao Q, Shen J (2025). Insulin-like growth factor-neutralizing antibodies for cancer therapy. Journal of Leukocyte Biology. Aug 21:qiaf122. doi: 10.1093/jleuko/qiaf122.

Li C, Xie Q, Ghosh S, Cao B, Du Y, Vo GV, Huang TY, Spruck C, Wang YA, Nephew KP, Shen J (2025). SUV39H1 maintains cancer stem cell chromatin state and properties in glioblastoma. JCI Insight. 10(5):e186344. doi: 10.1172/jci.insight.186344.

Cao B, Liu M, Xiao Z, Leng D, Zhou Y, Zhang Z, Lu Wang, Huang X, Ni Q, Cheng W, Assaraf GY, Zhao Q#, Shen J#, Zhu K# (2025). CV1-secreting sCAR-T cells potentiate the abscopal effect of microwave ablation in heterogeneous tumors. Cell Reports Medicine. 6(2):101965. doi: 10.1016/j.xcrm.2025.101965. (#co-corresponding)

Miller JC, Cao B, Shen J (2025). Head-to-Head: IL-21 triumphs over IL-15 in NK cell therapy for glioblastoma. Acta Biochimica et Biophysica Sinica. doi: 10.3724/abbs.2025009.

Poorva P, Mast J, Cao B, Shah MV, Pollok KE, Shen J (2025). Killing the killers: natural killer cell therapy targeting glioma stem cells in high-grade glioma. Molecular Therapy. S1525-0016(25)00168-6. doi: 10.1016/j.ymthe.2025.02.043.

Xie Q, Du Y, Ghosh S, Rajendran S, Cohen-Gadol AA, Baizabal M, Nephew KP, Han L, Shen J (2025). Multi-omic analysis identifies glioblastoma dependency on H3K9me3 methyltransferase activity. npj Precision Oncology. 9, Article number: 78.

Rajendran S, Farid EA, Chattopadhayay I, Zhang S, Sastry L, Xie Q, Shen J, Liu S, Wan J, Baylin SB, Rassool FV, Nephew KP (2025). Epigenetic reprogramming restores STING pathway activation in high-grade serous ovarian cancer. Cancer Research. 85(18_Supplement):a069-a069.

Du Y, Metcalfe S, Akunapuram S, Ghosh S, Spruck C, Richardson AM, Cohen-Gadol AA, Shen J (2024). Image-based assessment of natural killer cell activity against glioblastoma stem cells. FEBS Open Bio 14(6):1028-1034.

Du Y, Pollok KE, and Shen J (2023). Unlocking glioblastoma secrets: natural killer cell therapy against cancer stem cells. Cancers 15:5836.

Previous Publications: https://www.ncbi.nlm.nih.gov/myncbi/jia.shen.3/bibliography/public/

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