Daniel Radin
Education:
B.S. University of Rochester (2017)
Ph.D. Stony Brook University (2023)
Current Position:
8th Year MSTP
4th Year Medical Student
Advisor:
Stella Tsirka
Graduate Program:
Molecular & Cellular Pharmacology
Research Interest:
Glioblastoma is the most common and aggressive primary brain tumor in adults. Median survival time remains at 16-20 months despite multimodal treatment with surgical resection, radiation, temozolomide and tumor-treating fields therapy. After treatment with radiation, chemotherapy and tumor-treating fields, glioma cells initiate cytoprotective autophagy, a process by which tumor cells recycle old proteins and organelles to replete essential nutrients to overcome standard of care therapies. Autophagy contributes to treatment resistance in glioblastoma, limiting the efficacy of these therapies and providing an avenue for glioma recurrence. Antagonism of autophagy steps has recently gained attention as it may enhance the efficacy of classical chemotherapies and newer immune-stimulating therapies. The modulation of autophagy in the clinic is limited by the low potency of common autophagy inhibitors and the inability of newer ones to cross the blood-brain barrier. My thesis research leverages lucanthone, an anti-schistosomal agent which crosses the blood-brain barrier and was recently reported to act as an autophagy inhibitor in breast cancer cells. I found that lucanthone also acts as an autophagy inhibitor in glioma cells. Lucanthone suppresses the growth of stem-like glioma cells in culture and reduces the number of glioma stem cells in vivo. Lucanthone additionally slows glioma growth in vivo, normalizes tumor vasculature and reduces tumor hypoxia. Most notably, lucanthone retains its oncolytic activity against gliomas derived from temozolomide-resistant glioma cells. These findings detail that lucanthone may be useful in managing recurrent glioblastoma, a disease in which no modalities have been found to meaningfully extend patient survival.
Publications:
Radin DP, Shifman, S., Outhwaite, I. R., Sharma, A., Bases, R., Seeliger, M. A., & Tsirka, S. E. (2024). Lucanthone, a Potential PPT1 Inhibitor, Perturbs Stemness, Reduces Tumor Microtube Formation, and Slows the Growth of Temozolomide-Resistant Gliomas In Vivo. J Pharmacol Exp Ther, 389(1), 51-60.
Radin DP, Zhong, S., Cerne, R., Shoaib, M., Witkin, J. M., & Lippa, A. (2024). Low-Impact Ampakine CX1739 Exerts Pro-Cognitive Effects and Reverses Opiate-Induced Respiratory Depression in Rodents. Future Pharmacology, 4(1), 173-187.
Witkin, J. M., Radin DP, Rana, S., Fuller, D. D., Fusco, A. F., Demers, J. C., Pradeep Thakre, P., Smith, J. L., Lippa, A., & Cerne, R. (2024). AMPA receptors play an important role in the biological consequences of spinal cord injury: Implications for AMPA receptor modulators for therapeutic benefit. Biochem Pharmacol, 228, 116302.
Radin DP, Zhong, S., Cerne, R., Smith, J. L., Witkin, J. M., & Lippa, A. (2024). Preclinical Pharmacology of the Low-Impact Ampakine CX717. Future Pharmacology, 4(3), 494-509.
Radin DP, Cerne, R., Witkin, J., & Lippa, A. (2024). High-Impact AMPAkines Elevate Calcium Levels in Cortical Astrocytes by Mobilizing Endoplasmic Reticular Calcium Stores. Neuroglia, 5(3), 344-355.
Radin DP, Cerne, R., Witkin, J. M., & Lippa, A. (2024). Safety, Tolerability, and Pharmacokinetic Profile of the Low-Impact Ampakine CX1739 in Young Healthy Volunteers. Clin Pharmacol Drug Dev.
Radin DP, Zhong, S., Cerne, R., Shoaib, M., Witkin, J. M., & Lippa, A. (2024). Preclinical characterization of a water-soluble low-impact ampakine prodrug, CX1942 and its active moiety, CX1763. Future Med Chem, 1-12.
Radin DP, Zhong, S., Cerne, R., Witkin, J., & Lippa, A. (2024). High Impact AMPAkines Induce a Gq-Protein Coupled Endoplasmic Calcium Release in Cortical Neurons: A Possible Mechanism for Explaining the Toxicity of High Impact AMPAkines. Synapse, 78(5), e22310.
Hurley N, Srinivas, S, Fang J, Sun M, Hong S, Chien CT, Guo A, Khan TA, Li M, Cotlet M, Moretti F, Bourret E, Radin D, Tsirka SE, Shelly, M, Wong SS. Investigation of the photoluminescent properties, scintillation behaviour and toxicological profile of various magnesium tungstate nanoscale motifs. R Soc Open Sci, 2022. 9(12): p. 220994.
Smith GT, Radin DP, Tsirka SE. From protein-protein interactions to immune modulation: Therapeutic prospects of targeting Neuropilin-1 in high-grade glioma. Front Immunol, 2022. 13: p. 958620.
Radin D, Smith G, Moushiaveshi V, Wolf A, Bases R, Tsirka SE. (2022). Lucanthone targets lysosomes to perturb glioma proliferation, chemoresistance and stemness, and slows tumor growth in vivo. Frontiers in Oncology. 12:852940.
Caponegro, MD, Oh K, Madeira M, Radin D, Sterge N, Tayab M, Tsirka SE. (2021). A distinct microglial subset at the tumor-stroma interface of glioma. Glia. 69(7): 1767-1781.
Dai K, Radin D, Leonardi D. (2021). Deciphering the dual role and prognostic potential of PINK1 across cancer types. Neural Regeneration Research. 16(4): 659-665.
Radin D, Tsirka SE. (2020). Interactions between tumor cells, neurons, and microglia in the glioma microenvironment. International journal of molecular sciences. 21(22):8476.
Dai, K, Radin, D, Leonardi, D. (2019). PINK1 depletion sensitizes non-small cell lung cancer to glycolytic inhibitor 3-bromopyruvate:involvement of ROS and mitophagy. Pharmacological Reports. 71(6): 1184-1189.
Kumar, V, Radin, D, Leonardi D. (2019). Studies examining the synergy between Dihydrotanshinone and Temozolomide against MGMT+ glioblastoma cells in vitro: Predicting interactions with the blood-brain barrier. Biomedicine and Pharmacotherapy.109: 386-390.
Radin, D., Johnson, S., Purcell. R., Lippa A. (2018). Effects of chronic systemic low-impact ampakine treatment on neurotrophin expression in rat brain. Biomedicine and Pharmacotherapy. 6:105:540-544
Radin, D., Rogers, G., Hewitt, K., Purcell R., Lippa, A. (2018). Ampakines attenuate staurosporine-induced cell death in primary cortical Neurons: Implications in the ‘chemo-brain’ phenomenon. Anticancer research. 38(6):3461-3465
Radin, D., Li, Y., Rogers, G., Purcell, R., Lippa, A. (2018). Stargazin differentially modulates ampakine gating kinetics and pharmacology. Biochemical pharmacology. 148: 308-314.
Radin, D., Krebs, A,. Maqsudlu, A., Patel, P. (2017). Our ACE in the hole: Justifying the use of angiotensin-converting enzyme inhibitors as an adjuvant to standard chemotherapy. Anticancer Research. 38(1): 45-49.
Radin, D., Purcell. R., Lippa. A. (2017). Oncolytic properties of ampakines in vitro. Anticancer Research. 38(1): 265-269.
Purcell, R., Lynch, G., Gall, C… Radin, D., Lippa, A. (2017). Brain vacuolation resulting from administration of the type II ampakine CX717 is an artifact related to molecular structure and chemical reaction with tissue fixative agents. Toxicol Sci. 162(2):383-395.
Kumar, V., Radin, D., Leonardi, D. (2017). Probing the oncolytic and chemosensitizing effects of dihydrotanshinone in an in vitro glioblastoma model. Anticancer Research. 37: 6025-30.
Kim, D., Radin, D., Leonardi, D. (2017). Probing the molecular mechanisms governing the oncolytic activity of Paeonia suffruticosa on triple-negative breast cancer cells in vitro. Anticancer Research. 37(9). 4813-4819.
Radin, D., Patel, P. (2017). BDNF: an oncogene or tumor suppressor?. Anticancer Research. 37(8). 3983-3990.
Radin, D., Patel, P. (2017). A current perspective on the oncopreventive and oncolytic properties of selective serotonin reuptake inhibitors. Biomed and Pharmcother. 87. 636-639.
Radin, D., Zhong, S., Purcell, R, Lippa, A. (2016). Acute ampakine treatment ameliorates age-related deficits in long-term potentiation. Biomed and Pharmacother. 6(84). 806-809.
Radin, D., Patel. P. (2016). Delineating the molecular mechanisms of Tamoxifen’s oncolytic activity in estrogen receptor-negative cancers. European Journal of Pharmacology. 781. 173-180.
Radin, D., Lippa, A., Patel, P., Leonardi, D. (2015). Lifeguard inhibition of Fas-mediated apoptosis: A possible mechanism for explaining the cisplatin resistance of triple-negative breast cancer cells. Biomed and Pharmacother. 77. 161-166.
Patel, P., Radin, D., Leonardi, D. (2014). High Dose Estrogen Therapy: A Novel Mechanism of Action in Treating Estrogen Receptor-Negative Breast Cancers. Int. J. Sci. Eng. Res. 5(8). 289-295.
Zhou, L., Radin, D., Patel, P., Leonardi, D. (2014). The double life of hTERT: Identification of a novel function and an explanation of mechanism. Int. J. Sci. Eng. Res., 5(6), 643-647.
