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.

Recent Publications

• Xie Q, Wang B, Shen J (2025). A glioma stem cell-associated transcriptomic program predicts survival across adult and pediatric high grade gliomas. 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

• Qiu Z*, Zhao L*, Shen J*, Liang Z, Wu Q, Yang K, Min L, Gimple RC, Yang Q, Bhargava S, Jin C, Kim C, Hinz D, Dixit D, Bernatchez JA, Prager BC, Zhang G, Dong Z, Lv D, Wang X, Kim LJY, Zhu Z, Jones KA, Zheng Y, Siqueira-Neto JL, Chavez L, Fu X, Spruck C, Rich JN (2022). Transcription elongation machinery is a druggable dependency and potentiates immunotherapy in glioblastoma stem cells. Cancer Discovery 12:502-521.

• Jiang W, Jin L, Ju D, Lu Z, Wang C, Guo X, Zhao H, Shen S, Cheng Z, Shen J, Zong G, Chen J, Li K, Yang L, Feng Y, Shen J, Zhang EE, and Wan R (2022). The pancreatic clock is a key determinant of fibrosis progression and exocrine dysfunction. Science Translational Medicine 14(664):eabn3586.

• Lv D, Gimple R, Zhong C, Wu Q, Yang K, Prager B, Godugu B, Qiu Z, Zhao L, Zhang G, Dixit D, Lee D, Shen J, Li X, Xie Q, Wang X, Agnihotri S, Rich JN (2022). PDGF signaling inhibits mitophagy in glioblastoma stem cells through N6-methyladenosine. Developmental Cell 57:1466-1481.

• Grausam KB, Shen J, Breunig JJ, Spruck C, Shiao SL (2022). Utilizing ‘viral mimicry’ as a novel therapeutic approach in conjunction with anti-PD-1 immunotherapy increases immune activation and extends survival in a glioblastoma murine model. Cancer Research 82 (12_Supplement): 2057.

• Shen J*, Qiu Z*, Wu Q, Finlay D, Garcia G, Sun D, Rantala J, Barshop W, Hope JL, Gimple RC, Sangfelt O, Bradley LM, Wohlschlegel J, Rich JN, Spruck C (2021). FBXO44 promotes DNA replication-coupled repetitive element silencing in cancer cells. Cell 184:352-369. (Highlighted by Cancer Discovery 2021,11: 531.)

• Zhang G, Dong Z, Gimple RC, Wolin A, Wu Q, Qiu Z, Wood LM, Shen J, Jiang L, Zhao L, Lv D, Prager BC, Kim LJY, Zhang L, Anderson RL, Moore JK, Bao S, Keller TH, Lin G, Kang C, Hamerlik P, Zhao R, Ford HL, Rich JN (2021). Targeting EYA2 tyrosine phosphatase activity in glioblastoma stem cells induces mitotic catastrophe. Journal of Experimental Medicine 218: e20202669.

• Shen J, Spruck C (2021). Targeting FBXO44/SUV39H1 elicits tumor cell-specific DNA replication stress and viral mimicry. Cell Stress 5:37-39.

• Shen J*, Zhang T*, Cheng Z, Zhu N, Wang H, Lin L, Wang Z, Yi H, Hu M (2018). Lycorine inhibits glioblastoma multiforme growth through EGFR suppression. Journal of Experimental & Clinical Cancer Research 37:157.

• Shen J*, Wang B*, Zhang T, Zhu N, Wang Z, Jin J, He Y, Hu M. Suppression of non-small cell lung growth and metastasis by a novel small molecular activator of RECK (2018). Cellular Physiology and Biochemistry 45: 1807-1817.

• Wang B*, Shen J*, Wang Z, Liu J, Ning Z, Hu M (2018). Isomangiferin, a novel potent vascular endothelial growth factor receptor 2 kinase inhibitor, suppresses breast cancer growth, metastasis and angiogenesis. Journal of Breast Cancer 21:11-20.

• Jiang W*, Zhao S*, Shen J*, Guo L*, Sun Y, Zhu Y, Ma Z, Zhang X, Hu Y, Xiao W, Li K, Li S, Zhou L, Huang L, Lu Z, Feng Y, Xiao J, Zhang EE, Yang L, Wan R. The MiR-135b–BMAL1–YY1 loop disturbs pancreatic clockwork to promote tumourigenesis and chemoresistance (2018). Cell Death & Disease 9:149.

• Shen J*, Ma H*, Zhang T, Liu H, Yu L, Li G, Li H, Hu M (2017). Magnolol inhibits the growth of non-small cell lung cancer via inhibiting microtubule polymerization. Cellular Physiology and Biochemistry 42: 1789-1801.

• Jin R*, Shen J*, Zhang T*, Liu Q, Liao C, Ma H, Li S, Yu Z (2017). The highly expressed COL4A1 genes contributes to the proliferation and migration of the invasive ductal carcinomas. Oncotarget 8:58172-58183.

• Shen J, Spruck C (2017). F-Box proteins in epigenetic regulation of cancer. Oncotarget 8,110650.

• Wang J, Li W, Ge Y, Shen J, Zhao Y, Zhang Y, Yuan J (2017). Design and synthesis of porous TiO2@C nanotube bundles with enhanced supercapacitive performance. Ceramics International 43, 2876-2880.

• Li C, Hu J, Li W, Song G, Shen J (2017). Combined bortezomib-based chemotherapy and p53 gene therapy using hollow mesoporous silica nanospheres for p53 mutant non-small cell lung cancer treatment. Biomaterials Science 5, 77-88. 

• Shen J*, Sheng X*, Chang ZN*, Wu Q, Wang S, Xuan Z, Li D, Wu Y, Shang Y, Kong X, Yu L, Ruan K, Hu H, Huang Y, Hui L, Xie D, Wang F, Hu R (2014). Iron metabolism regulates p53 signaling through direct heme-p53 interaction and modulating localization, stability and function of p53. Cell Reports 7:1-14. (Highlighted by Cell Chemical Biology 2014, 21: 431-432.)

• Shen J*, Song G*, An M, Li X, Wu N, Ruan K, Hu J, Hu R (2014). The use of hollow mesoporous silica nanospheres to encapsulate bortezomib and improve efficacy for non-small cell lung cancer therapy. Biomaterials 1: 316-26.

• Shen J, Sheng X, Chang Z, Wu Q, Xie D, Wang F, Hu R (2014). The heme–p53 interaction: Linking iron metabolism to p53 signaling and tumorigenesis. Molecular & Cellular Oncology 3(1): e965642.

• Song G*, Shen J*, Jiang F, Hu R, Li W, An L, Zou R, Chen Z, Qin Z, Hu J (2014). Hydrophilic molybdenum oxide nanomaterials with controlled morphology and strong plasmonic absorption for photothermal ablation of cancer cells. ACS Applied Materials & Interfaces 6:3915-22.

• Shen J, Zhang S, Li Y, Zhang W, Chen J, Zhang M, Wang T, Jiang L, Zou X, Wong J, Li X, Cui Y, Wang C (2011). P14ARF inhibits the functions of adenovirus E1A oncoprotein. Biochemical Journal 434:275-85.