Research Synopsis
Research Synopsis
Threats:
(1) Glioblastoma (GBM), the most aggressive adult brain cancer, claims over 15,000 lives annually in the U.S. Despite surgery, radiation, and chemotherapy, the median survival is a grim 15 months.
(2) Diffuse Intrinsic Pontine Glioma (DIPG), which primarily affects children aged 5 to 10, targets the brainstem with devastating precision. This inoperable, chemotherapy-resistant tumor has a median survival of less than 1 year.
Killers:
Beneath these tumors lurks a more elusive enemy - cancer stem cells (CSCs), also known as tumor-initiating cells. Like normal stem cells, CSCs self-renew, differentiate, and resist traditional therapies, fueling tumor growth, recurrence, and metastasis. In GBM and DIPG, these CSCs are the root cause of treatment failure. Without eliminating CSCs, a cancer cure is unlikely.
Mission:
We are committed to defeating these CSCs in both adult and childhood brain cancers. Our approach integrates computational analysis with precision immunotherapy to revolutionize treatment outcomes.
Battle Plan:
(1) Precision Targeting: Leveraging computational and functional genomics, we target key regulators of CSC survival - including epigenetic regulators, transcription factors, and E3 ubiquitin ligases.
(2) Immune Arsenal: We empower the body's natural defenders, NK cells and T cells, to destroy CSCs lurking within brain tumors.
Publications
Recent Publications
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. SSRN: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=5365407
Zhao Q, Shen J (2025). Insulin-like growth factor-neutralizing antibodies for cancer therapy. Journal of Leukocyte Biology. 2025 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.
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.
Supports