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1. Ultrasound-mediated delivery of doxorubicin to the brain results in immune modulation and improved responses to PD-1 blockade in gliomas

Author

Arrieta, Víctor A., Gould, Andrew, Kim, Kwang-Soo, Habashy, Karl J., Dmello, Crismita, Vázquez-Cervantes, Gustavo I., Palacín-Aliana, Irina, McManus, Graysen, Amidei, Christina, Gomez, Cristal, Dhiantravan, Silpol, Chen, Li, Zhang, Daniel Y., Saganty, Ruth, Cholak, Meghan E., Pandey, Surya, McCord, Matthew, McCortney, Kathleen, Castro, Brandyn, Ward, Rachel, Muzzio, Miguel, Bouchoux, Guillaume, Desseaux, Carole, Canney, Michael, Carpentier, Alexandre, Zhang, Bin, Miska, Jason M., Lesniak, Maciej S., Horbinski, Craig M., Lukas, Rimas V., Stupp, Roger, Lee-Chang, Catalina, and Sonabend, Adam M.

Published
2024
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2. Checkpoint kinase 1/2 inhibition potentiates anti-tumoral immune response and sensitizes gliomas to immune checkpoint blockade

Author

Dmello, Crismita, Zhao, Junfei, Chen, Li, Gould, Andrew, Castro, Brandyn, Arrieta, Victor A, Zhang, Daniel Y, Kim, Kwang-Soo, Kanojia, Deepak, Zhang, Peng, Miska, Jason, Yeeravalli, Ragini, Habashy, Karl, Saganty, Ruth, Kang, Seong Jae, Fares, Jawad, Liu, Connor, Dunn, Gavin, Bartom, Elizabeth, Schipma, Matthew J, Hsu, Patrick D, Alghamri, Mahmoud S, Lesniak, Maciej S, Heimberger, Amy B, Rabadan, Raul, Lee-Chang, Catalina, and Sonabend, Adam M

Subjects
Rare Diseases, Brain Cancer, Cancer, Brain Disorders, Neurosciences, Clinical Research, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Humans, Animals, Mice, Immune Checkpoint Inhibitors, B7-H1 Antigen, Checkpoint Kinase 1, Glioma, Glioblastoma, CD8-Positive T-Lymphocytes, Immunity, Tumor Microenvironment
Abstract

Whereas the contribution of tumor microenvironment to the profound immune suppression of glioblastoma (GBM) is clear, tumor-cell intrinsic mechanisms that regulate resistance to CD8 T cell mediated killing are less understood. Kinases are potentially druggable targets that drive tumor progression and might influence immune response. Here, we perform an in vivo CRISPR screen to identify glioma intrinsic kinases that contribute to evasion of tumor cells from CD8 T cell recognition. The screen reveals checkpoint kinase 2 (Chek2) to be the most important kinase contributing to escape from CD8 T-cell recognition. Genetic depletion or pharmacological inhibition of Chek2 with blood-brain-barrier permeable drugs that are currently being evaluated in clinical trials, in combination with PD-1 or PD-L1 blockade, lead to survival benefit in multiple preclinical glioma models. Mechanistically, loss of Chek2 enhances antigen presentation, STING pathway activation and PD-L1 expression in mouse gliomas. Analysis of human GBMs demonstrates that Chek2 expression is inversely associated with antigen presentation and T-cell activation. Collectively, these results support Chek2 as a promising target for enhancement of response to immune checkpoint blockade therapy in GBM.

Published
2023

3. Translocon-associated Protein Subunit SSR3 Determines and Predicts Susceptibility to Paclitaxel in Breast Cancer and Glioblastoma.

Author

Dmello, Crismita, Sonabend, Aarón, Arrieta, Victor A, Zhang, Daniel Y, Kanojia, Deepak, Chen, Li, Gould, Andrew, Zhang, Jiangshan, Kang, Seong Jae, Winter, Jan, Horbinski, Craig, Amidei, Christina, Győrffy, Balázs, Cordero, Alex, Chang, Catalina Lee, Castro, Brandyn, Hsu, Patrick, Ahmed, Atique U, Lesniak, Maciej S, Stupp, Roger, and Sonabend, Adam M

Subjects
Neurosciences, Genetics, Breast Cancer, Brain Disorders, Rare Diseases, Cancer, Brain Cancer, Animals, Antineoplastic Agents, Phytogenic, Biomarkers, Pharmacological, Brain Neoplasms, Breast Neoplasms, Calcium-Binding Proteins, Cell Line, Tumor, Drug Resistance, Neoplasm, Endoribonucleases, Female, Glioblastoma, Humans, Membrane Glycoproteins, Mice, Paclitaxel, Prospective Studies, Protein Serine-Threonine Kinases, Receptors, Cytoplasmic and Nuclear, Receptors, Peptide, Xenograft Model Antitumor Assays, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

PurposePaclitaxel (PTX) is one of the most potent and commonly used chemotherapies for breast and pancreatic cancer. Several ongoing clinical trials are investigating means of enhancing delivery of PTX across the blood-brain barrier for glioblastomas. Despite the widespread use of PTX for breast cancer, and the initiative to repurpose this drug for gliomas, there are no predictive biomarkers to inform which patients will likely benefit from this therapy.Experimental designTo identify predictive biomarkers for susceptibility to PTX, we performed a genome-wide CRISPR knockout (KO) screen using human glioma cells. The genes whose KO was most enriched in the CRISPR screen underwent further selection based on their correlation with survival in the breast cancer patient cohorts treated with PTX and not in patients treated with other chemotherapies, a finding that was validated on a second independent patient cohort using progression-free survival.ResultsCombination of CRISPR screen results with outcomes from patients with taxane-treated breast cancer led to the discovery of endoplasmic reticulum (ER) protein SSR3 as a putative predictive biomarker for PTX. SSR3 protein levels showed positive correlation with susceptibility to PTX in breast cancer cells, glioma cells, and in multiple intracranial glioma xenografts models. KO of SSR3 turned the cells resistant to PTX while its overexpression sensitized the cells to PTX. Mechanistically, SSR3 confers susceptibility to PTX through regulation of phosphorylation of ER stress sensor IRE1α.ConclusionsOur hypothesis generating study showed SSR3 as a putative biomarker for susceptibility to PTX, warranting its prospective clinical validation.

Published
2022

5. Repeated blood–brain barrier opening with an implantable ultrasound device for delivery of albumin-bound paclitaxel in patients with recurrent glioblastoma: a phase 1 trial

Author

Sonabend, Adam M, Gould, Andrew, Amidei, Christina, Ward, Rachel, Schmidt, Karyn A, Zhang, Daniel Y, Gomez, Cristal, Bebawy, John F, Liu, Benjamin P, Bouchoux, Guillaume, Desseaux, Carole, Helenowski, Irene B, Lukas, Rimas V, Dixit, Karan, Kumthekar, Priya, Arrieta, Víctor A, Lesniak, Maciej S, Carpentier, Alexandre, Zhang, Hui, Muzzio, Miguel, Canney, Michael, and Stupp, Roger

Published
2023
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6. Molecular landscapes of human hippocampal immature neurons across lifespan

Author

Zhou, Yi, Su, Yijing, Li, Shiying, Kennedy, Benjamin C., Zhang, Daniel Y., Bond, Allison M., Sun, Yusha, Jacob, Fadi, Lu, Lu, Hu, Peng, Viaene, Angela N., Helbig, Ingo, Kessler, Sudha K., Lucas, Timothy, Salinas, Ryan D., Gu, Xiaosong, Chen, H. Isaac, Wu, Hao, Kleinman, Joel E., Hyde, Thomas M., Nauen, David W., Weinberger, Daniel R., Ming, Guo-li, and Song, Hongjun

Published
2022
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7. Exposure to the antiretroviral drug dolutegravir impairs structure and neurogenesis in a forebrain organoid model of human embryonic cortical development.

Author

LaNoce, Emma, Zhang, Daniel Y., Garcia-Epelboim, Alan, Su, Yijing, Sun, Yusha, Alepa, Giana, Angelucci, Angelina R., Akay-Espinoza, Cagla, Jordan-Sciutto, Kelly L., Song, Hongjun, Ming, Guo-li, and Christian, Kimberly M.

Subjects
INDUCED pluripotent stem cells, AMINO acid transport, NEURAL development, ANTIRETROVIRAL agents, NEURAL tube defects, CELL cycle regulation, DEVELOPMENTAL neurobiology
Abstract

Introduction: For many therapeutic drugs, including antiretroviral drugs used to treat people living with HIV-1 (PLWH), we have little data on the potential effects on the developing human brain due to limited access to tissue and historical constraints on the inclusion of pregnant populations in clinical trials. Human induced pluripotent stem cells (iPSCs) offer a new avenue to gain insight on how drugs may impact human cell types representative of the developing central nervous system. To prevent vertical transmission of HIV and promote the health of pregnant PLWH, antiretroviral therapy must be initiated and/or maintained throughout pregnancy. However, many antiretroviral drugs are approved for widespread use following clinical testing only in non-pregnant populations and there may be limited information on potential teratogenicity until pregnancy outcomes are evaluated. The integrase strand transfer inhibitor dolutegravir (DTG) is a frontline antiretroviral drug that is effective in viral suppression of HIV but was previously reported to be associated with a slight increase in the risk for neural tube defects in one study, although this has not been replicated in other cohorts. Methods: To directly investigate the potential impact of DTG on human cortical neurogenesis, we measured the effects of daily drug exposure on the early stages of corticogenesis in a human iPSC-based forebrain organoid model. We quantified organoid size and structure and analyzed gene and protein expression to evaluate the impact of several doses of DTG on organoid development. Results: We observed deficits in organoid structure and impaired neurogenesis in DTG-treated organoids compared to vehicle-treated control organoids after 20 or 40 days in culture. Our highest dose of DTG (10 μM) resulted in significantly smaller organoids with a reduced density of neural rosette structures compared to vehicle-treated controls. Mechanistically, RNA-sequencing and immunohistological analysis suggests dysregulated amino acid transport and activation of the integrated stress response in the DTG-treated organoids, and functionally, a small molecule integrated stress response inhibitor (ISRIB) could partially rescue increased expression of proteins related to cell cycle regulation. Discussion: Together, these results illustrate the potential for human iPSC-based strategies to reveal biological processes during neurogenesis that may be affected by therapeutic drugs and provide complementary data in relevant human cell types to augment preclinical investigations of drug safety during pregnancy. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Fc-enhanced anti-CTLA-4, anti-PD-1, doxorubicin, and ultrasound-mediated blood–brain barrier opening: A novel combinatorial immunotherapy regimen for gliomas.

Author

Kim, Kwang-Soo, Habashy, Karl, Gould, Andrew, Zhao, Junfei, Najem, Hinda, Amidei, Christina, Saganty, Ruth, Arrieta, Víctor A, Dmello, Crismita, Chen, Li, Zhang, Daniel Y, Castro, Brandyn, Billingham, Leah, Levey, Daniel, Huber, Olivia, Marques, Marilyn, Savitsky, David A, Morin, Benjamin M, Muzzio, Miguel, and Canney, Michael

Published
2024
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9. Brain-wide neuronal circuit connectome of human glioblastoma

Author

Sun, Yusha, primary, Wang, Xin, additional, Zhang, Daniel Y, additional, Zhang, Zhijian, additional, Bhattarai, Janardhan P, additional, Wang, Yingqi, additional, Dong, Weifan, additional, Zhang, Feng, additional, Park, Kristen H, additional, Galanaugh, Jamie, additional, Sambangi, Abhijeet, additional, Yang, Qian, additional, Kim, Sang Hoon, additional, Wheeler, Garrett, additional, Goncalves, Tiago, additional, Wang, Qing, additional, Geschwind, Daniel, additional, Kawaguchi, Riki, additional, Wang, Huadong, additional, Xu, Fuqiang, additional, Binder, Zev A, additional, Chen, Isaac H, additional, Pai, Emily Ling-Lin, additional, Stone, Sara, additional, Nasrallah, MacLean, additional, Christian, Kimberly M, additional, Fuccillo, Marc, additional, O'Rourke, Donald M, additional, Ma, Minghong, additional, Ming, Guo-li, additional, and Song, Hongjun, additional

Published
2024
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10. Advances in Blood-Brain Barrier Disruption to Facilitate Drug Delivery for Infiltrative Gliomas

Author

Gould, Andrew, primary, Arrieta Gonzales, Victor Andrés, additional, Dmello, Crismita Clement, additional, Saganty, Ruth, additional, Lukas, Rimas V., additional, Zhang, Daniel Y., additional, Heimberger, Amy B., additional, Canney, Michael, additional, Carpentier, Alexandre, additional, Desseaux, Carole, additional, Bouchoux, Guillaume, additional, Stupp, Roger, additional, and Sonabend, Adam M., additional

Published
2023
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12. Figure S3 from CD8+ T-cell–Mediated Immunoediting Influences Genomic Evolution and Immune Evasion in Murine Gliomas

Author

Kane, Joshua R., primary, Zhao, Junfei, primary, Tsujiuchi, Takashi, primary, Laffleur, Brice, primary, Arrieta, Víctor A., primary, Mahajan, Aayushi, primary, Rao, Ganesh, primary, Mela, Angeliki, primary, Dmello, Crismita, primary, Chen, Li, primary, Zhang, Daniel Y., primary, González-Buendia, Edgar, primary, Lee-Chang, Catalina, primary, Xiao, Ting, primary, Rothschild, Gerson, primary, Basu, Uttiya, primary, Horbinski, Craig, primary, Lesniak, Maciej S., primary, Heimberger, Amy B., primary, Rabadan, Raul, primary, Canoll, Peter, primary, and Sonabend, Adam M., primary

Published
2023
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13. Data from Translocon-associated Protein Subunit SSR3 Determines and Predicts Susceptibility to Paclitaxel in Breast Cancer and Glioblastoma

Author

Dmello, Crismita, primary, Sonabend, Aarón, primary, Arrieta, Victor A., primary, Zhang, Daniel Y., primary, Kanojia, Deepak, primary, Chen, Li, primary, Gould, Andrew, primary, Zhang, Jiangshan, primary, Kang, Seong Jae, primary, Winter, Jan, primary, Horbinski, Craig, primary, Amidei, Christina, primary, Győrffy, Balázs, primary, Cordero, Alex, primary, Chang, Catalina Lee, primary, Castro, Brandyn, primary, Hsu, Patrick, primary, Ahmed, Atique U., primary, Lesniak, Maciej S., primary, Stupp, Roger, primary, and Sonabend, Adam M., primary

Published
2023
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14. Supplementary Figure from Translocon-associated Protein Subunit SSR3 Determines and Predicts Susceptibility to Paclitaxel in Breast Cancer and Glioblastoma

Author

Dmello, Crismita, primary, Sonabend, Aarón, primary, Arrieta, Victor A., primary, Zhang, Daniel Y., primary, Kanojia, Deepak, primary, Chen, Li, primary, Gould, Andrew, primary, Zhang, Jiangshan, primary, Kang, Seong Jae, primary, Winter, Jan, primary, Horbinski, Craig, primary, Amidei, Christina, primary, Győrffy, Balázs, primary, Cordero, Alex, primary, Chang, Catalina Lee, primary, Castro, Brandyn, primary, Hsu, Patrick, primary, Ahmed, Atique U., primary, Lesniak, Maciej S., primary, Stupp, Roger, primary, and Sonabend, Adam M., primary

Published
2023
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15. Data from CD8+ T-cell–Mediated Immunoediting Influences Genomic Evolution and Immune Evasion in Murine Gliomas

Author

Kane, Joshua R., primary, Zhao, Junfei, primary, Tsujiuchi, Takashi, primary, Laffleur, Brice, primary, Arrieta, Víctor A., primary, Mahajan, Aayushi, primary, Rao, Ganesh, primary, Mela, Angeliki, primary, Dmello, Crismita, primary, Chen, Li, primary, Zhang, Daniel Y., primary, González-Buendia, Edgar, primary, Lee-Chang, Catalina, primary, Xiao, Ting, primary, Rothschild, Gerson, primary, Basu, Uttiya, primary, Horbinski, Craig, primary, Lesniak, Maciej S., primary, Heimberger, Amy B., primary, Rabadan, Raul, primary, Canoll, Peter, primary, and Sonabend, Adam M., primary

Published
2023
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16. Supplementary Materials and Data from Ultrasound-mediated Delivery of Paclitaxel for Glioma: A Comparative Study of Distribution, Toxicity, and Efficacy of Albumin-bound Versus Cremophor Formulations

Author

Zhang, Daniel Y., primary, Dmello, Crismita, primary, Chen, Li, primary, Arrieta, Victor A., primary, Gonzalez-Buendia, Edgar, primary, Kane, J. Robert, primary, Magnusson, Lisa P., primary, Baran, Aneta, primary, James, C. David, primary, Horbinski, Craig, primary, Carpentier, Alexandre, primary, Desseaux, Carole, primary, Canney, Michael, primary, Muzzio, Miguel, primary, Stupp, Roger, primary, and Sonabend, Adam M., primary

Published
2023
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17. Supplementary Table from Translocon-associated Protein Subunit SSR3 Determines and Predicts Susceptibility to Paclitaxel in Breast Cancer and Glioblastoma

Author

Dmello, Crismita, primary, Sonabend, Aarón, primary, Arrieta, Victor A., primary, Zhang, Daniel Y., primary, Kanojia, Deepak, primary, Chen, Li, primary, Gould, Andrew, primary, Zhang, Jiangshan, primary, Kang, Seong Jae, primary, Winter, Jan, primary, Horbinski, Craig, primary, Amidei, Christina, primary, Győrffy, Balázs, primary, Cordero, Alex, primary, Chang, Catalina Lee, primary, Castro, Brandyn, primary, Hsu, Patrick, primary, Ahmed, Atique U., primary, Lesniak, Maciej S., primary, Stupp, Roger, primary, and Sonabend, Adam M., primary

Published
2023
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18. Supplementary Data from Translocon-associated Protein Subunit SSR3 Determines and Predicts Susceptibility to Paclitaxel in Breast Cancer and Glioblastoma

Author

Dmello, Crismita, primary, Sonabend, Aarón, primary, Arrieta, Victor A., primary, Zhang, Daniel Y., primary, Kanojia, Deepak, primary, Chen, Li, primary, Gould, Andrew, primary, Zhang, Jiangshan, primary, Kang, Seong Jae, primary, Winter, Jan, primary, Horbinski, Craig, primary, Amidei, Christina, primary, Győrffy, Balázs, primary, Cordero, Alex, primary, Chang, Catalina Lee, primary, Castro, Brandyn, primary, Hsu, Patrick, primary, Ahmed, Atique U., primary, Lesniak, Maciej S., primary, Stupp, Roger, primary, and Sonabend, Adam M., primary

Published
2023
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19. Supplementary Legend from CD8+ T-cell–Mediated Immunoediting Influences Genomic Evolution and Immune Evasion in Murine Gliomas

Author

Kane, Joshua R., primary, Zhao, Junfei, primary, Tsujiuchi, Takashi, primary, Laffleur, Brice, primary, Arrieta, Víctor A., primary, Mahajan, Aayushi, primary, Rao, Ganesh, primary, Mela, Angeliki, primary, Dmello, Crismita, primary, Chen, Li, primary, Zhang, Daniel Y., primary, González-Buendia, Edgar, primary, Lee-Chang, Catalina, primary, Xiao, Ting, primary, Rothschild, Gerson, primary, Basu, Uttiya, primary, Horbinski, Craig, primary, Lesniak, Maciej S., primary, Heimberger, Amy B., primary, Rabadan, Raul, primary, Canoll, Peter, primary, and Sonabend, Adam M., primary

Published
2023
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24. CTNI-37. REPEATED OPENING OF THE BLOOD-BRAIN BARRIER WITH THE SKULL-IMPLANTABLE SONOCLOUD-9 (SC9) DEVICE: PHASE 1 TRIAL OF NAB-PACLITAXEL AND SC9 IN RECURRENT GLIOBLASTOMA

Author

Sonabend, Adam M, primary, Gould, Andrew, additional, Luan, Yu, additional, Hou, Ye, additional, Kobayashi, Mikoto A, additional, Castro, Brandyn, additional, Zhang, Daniel Y, additional, Chen, Li, additional, Korobova, Farida, additional, Amidei, Christina, additional, Youngblood, Mark, additional, Bebawy, John Patrick F, additional, Liu, Benjamin, additional, Horbinski, Craig, additional, Desseaux, Carole, additional, Helenowski, Irene B, additional, Zhang, Hui, additional, Muzzio, Miguel, additional, Yue, Feng, additional, Canney, Michael, additional, and Stupp, Roger, additional

Published
2022
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26. Repeated opening of the blood-brain barrier with the skull-implantable SonoCloud-9 (SC9) device: Phase 1 trial of nab-paclitaxel and SC9 in recurrent glioblastoma.

Author

Sonabend, Adam M., primary, Gould, Andrew, additional, Luan, Yu, additional, Hou, Ye, additional, Chen, Li, additional, Kobayashi, Mikoto A., additional, Castro, Brandyn A., additional, Zhang, Daniel Y., additional, Korobova, Farida V., additional, Amidei, Christina, additional, Bebawy, John F., additional, Liu, Benjamin P, additional, Horbinski, Craig M., additional, Desseaux, Carole, additional, Helenowski, Irene B., additional, Zhang, Hui, additional, Muzzio, Miguel M, additional, Yue, Feng, additional, Canney, Michael, additional, and Stupp, Roger, additional

Published
2022
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29. Generation of hypothalamic arcuate organoids from human induced pluripotent stem cells

Author

Huang, Wei-Kai, primary, Wong, Samuel Zheng Hao, additional, Pather, Sarshan R., additional, Nguyen, Phuong T.T., additional, Zhang, Feng, additional, Zhang, Daniel Y., additional, Zhang, Zhijian, additional, Lu, Lu, additional, Fang, Wanqi, additional, Chen, Luyun, additional, Fernandes, Analiese, additional, Su, Yijing, additional, Song, Hongjun, additional, and Ming, Guo-li, additional

Published
2021
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34. Human Pluripotent Stem Cell-Derived Neural Cells and Brain Organoids Reveal SARS-CoV-2 Neurotropism Predominates in Choroid Plexus Epithelium

Author

Jacob, Fadi, primary, Pather, Sarshan R., additional, Huang, Wei-Kai, additional, Zhang, Feng, additional, Wong, Samuel Zheng Hao, additional, Zhou, Haowen, additional, Cubitt, Beatrice, additional, Fan, Wenqiang, additional, Chen, Catherine Z., additional, Xu, Miao, additional, Pradhan, Manisha, additional, Zhang, Daniel Y., additional, Zheng, Wei, additional, Bang, Anne G., additional, Song, Hongjun, additional, Carlos de la Torre, Juan, additional, and Ming, Guo-li, additional

Published
2020
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35. Activation of 4-1BBL+ B cells with CD40 agonism and IFNγ elicits potent immunity against glioblastoma

Author

Lee-Chang, Catalina, primary, Miska, Jason, additional, Hou, David, additional, Rashidi, Aida, additional, Zhang, Peng, additional, Burga, Rachel A., additional, Jusué-Torres, Ignacio, additional, Xiao, Ting, additional, Arrieta, Victor A., additional, Zhang, Daniel Y., additional, Lopez-Rosas, Aurora, additional, Han, Yu, additional, Sonabend, Adam M., additional, Horbinski, Craig M., additional, Stupp, Roger, additional, Balyasnikova, Irina V., additional, and Lesniak, Maciej S., additional

Published
2020
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36. CD8+ T-cell–Mediated Immunoediting Influences Genomic Evolution and Immune Evasion in Murine Gliomas

Author

Kane, Joshua R., primary, Zhao, Junfei, additional, Tsujiuchi, Takashi, additional, Laffleur, Brice, additional, Arrieta, Víctor A., additional, Mahajan, Aayushi, additional, Rao, Ganesh, additional, Mela, Angeliki, additional, Dmello, Crismita, additional, Chen, Li, additional, Zhang, Daniel Y., additional, González-Buendia, Edgar, additional, Lee-Chang, Catalina, additional, Xiao, Ting, additional, Rothschild, Gerson, additional, Basu, Uttiya, additional, Horbinski, Craig, additional, Lesniak, Maciej S., additional, Heimberger, Amy B., additional, Rabadan, Raul, additional, Canoll, Peter, additional, and Sonabend, Adam M., additional

Published
2020
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37. Human Pluripotent Stem Cell-Derived Neural Cells and Brain Organoids Reveal SARS-CoV-2 Neurotropism

Author

Jacob, Fadi, primary, Pather, Sarshan R., additional, Huang, Wei-Kai, additional, Wong, Samuel Zheng Hao, additional, Zhou, Haowen, additional, Zhang, Feng, additional, Cubitt, Beatrice, additional, Chen, Catherine Z., additional, Xu, Miao, additional, Pradhan, Manisha, additional, Zhang, Daniel Y., additional, Zheng, Wei, additional, Bang, Anne G., additional, Song, Hongjun, additional, de a Torre, Juan Carlos, additional, and Ming, Guo-li, additional

Published
2020
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38. Ultrasound-mediated Delivery of Paclitaxel for Glioma: A Comparative Study of Distribution, Toxicity, and Efficacy of Albumin-bound Versus Cremophor Formulations

Author

Zhang, Daniel Y., primary, Dmello, Crismita, additional, Chen, Li, additional, Arrieta, Victor A., additional, Gonzalez-Buendia, Edgar, additional, Kane, J. Robert, additional, Magnusson, Lisa P., additional, Baran, Aneta, additional, James, C. David, additional, Horbinski, Craig, additional, Carpentier, Alexandre, additional, Desseaux, Carole, additional, Canney, Michael, additional, Muzzio, Miguel, additional, Stupp, Roger, additional, and Sonabend, Adam M., additional

Published
2020
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39. A Patient-Derived Glioblastoma Organoid Model and Biobank Recapitulates Inter- and Intra-tumoral Heterogeneity

Author

Jacob, Fadi, primary, Salinas, Ryan D., additional, Zhang, Daniel Y., additional, Nguyen, Phuong T.T., additional, Schnoll, Jordan G., additional, Wong, Samuel Zheng Hao, additional, Thokala, Radhika, additional, Sheikh, Saad, additional, Saxena, Deeksha, additional, Prokop, Stefan, additional, Liu, Di-ao, additional, Qian, Xuyu, additional, Petrov, Dmitriy, additional, Lucas, Timothy, additional, Chen, H. Isaac, additional, Dorsey, Jay F., additional, Christian, Kimberly M., additional, Binder, Zev A., additional, Nasrallah, MacLean, additional, Brem, Steven, additional, O’Rourke, Donald M., additional, Ming, Guo-li, additional, and Song, Hongjun, additional

Published
2020
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40. IMMU-42. CD8+ T-CELLS MEDIATE IMMUNOEDITING, AND INFLUENCE GENOTYPE, TUMOR ONCOGENIC PATHWAYS AND MICROENVIRONMENT DURING PROGRESSION OF MURINE GLIOMAS

Author

Robert Kane, J, primary, Zhao, Junfei, additional, Tsujiuchi, Takashi, additional, Laffleur, Brice, additional, Mahajan, Aayushi, additional, Rao, Ganesh, additional, Mela, Angeliki, additional, Dmello, Crismita, additional, Arrieta, Victor A, additional, Chen, Li, additional, Zhang, Daniel Y, additional, Lee-Chang, Catalina, additional, Xiao, Ting, additional, Rothschild, Gerson, additional, Basu, Uttiya, additional, Horbinski, Craig, additional, Lesniak, Maciej S, additional, Heimberger, Amy, additional, Rabadan, Raul, additional, Canoll, Peter D, additional, and Sonabend, Adam, additional

Published
2019
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41. CD8+ T-cell-mediated immunoediting influences genomic evolution and immune evasion in murine gliomas

Author

Kane, J. Robert, primary, Zhao, Junfei, additional, Tsujiuchi, Takashi, additional, Laffleur, Brice, additional, Mahajan, Aayushi, additional, Rao, Ganesh, additional, Mela, Angeliki, additional, Dmello, Crismita, additional, Arrieta, Víctor A., additional, Chen, Li, additional, Zhang, Daniel Y., additional, Gonzalez-Buendia, Edgar, additional, Lee-Chang, Catalina, additional, Xiao, Ting, additional, Rothschild, Gerson, additional, Basu, Uttiya, additional, Horbinski, Craig, additional, Lesniak, Maciej S., additional, Heimberger, Amy B., additional, Rabadan, Raul, additional, Canoll, Peter D., additional, and Sonabend, Adam M., additional

Published
2019
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43. Photoactivatable Sensors for Detecting Mobile Zinc

Author

Goldberg, Jacob M., primary, Wang, Fang, additional, Sessler, Chanan D., additional, Vogler, Nathan W., additional, Zhang, Daniel Y., additional, Loucks, William H., additional, Tzounopoulos, Thanos, additional, and Lippard, Stephen J., additional

Published
2018
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44. Peptide-Based, Two-Fluorophore, Ratiometric Probe for Quantifying Mobile Zinc in Biological Solutions

Author

Massachusetts Institute of Technology. Department of Chemistry, Zhang, Daniel Y., Lippard, Stephen J., Radford, Robert John, Azrad, Maria, Demark-Wahnefried, Wendy, Frederickson, Christopher J., Massachusetts Institute of Technology. Department of Chemistry, Zhang, Daniel Y., Lippard, Stephen J., Radford, Robert John, Azrad, Maria, Demark-Wahnefried, Wendy, and Frederickson, Christopher J.

Abstract

Small-molecule fluorescent sensors are versatile agents for detecting mobile zinc in biology. Capitalizing on the abundance of validated mobile zinc probes, we devised a strategy for repurposing existing intensity-based sensors for quantitative applications. Using solid-phase peptide synthesis, we conjugated a zinc-sensitive Zinpyr-1 derivative and a zinc-insensitive 7-hydroxycoumarin derivative onto opposite ends of a rigid P₉K peptide scaffold to create HcZ9, a ratiometric fluorescent probe for mobile zinc. A plate reader-based assay using HcZ9 was developed, the accuracy of which is comparable to that of atomic absorption spectroscopy. We investigated zinc accumulation in prostatic cells and zinc levels in human seminal fluid. When normal and tumorigenic cells are bathed in zinc-enriched media, cellular mobile zinc is buffered and changes slightly, but total zinc levels increase significantly. Quantification of mobile and total zinc levels in human seminal plasma revealed that the two are positively correlated with a Pearson’s coefficient of 0.73., National Institute of General Medical Sciences (U.S.) (GM065519)

Published
2017

46. Modulation of extrasynaptic NMDA receptors by synaptic and tonic zinc

Author

Massachusetts Institute of Technology. Department of Chemistry, Radford, Robert J., Zastrow, Melissa, Zhang, Daniel Y., Apfel, Ulf-Peter, Lippard, Stephen J., Anderson, Charles T., Tzounopoulos, Thanos, Massachusetts Institute of Technology. Department of Chemistry, Radford, Robert J., Zastrow, Melissa, Zhang, Daniel Y., Apfel, Ulf-Peter, Lippard, Stephen J., Anderson, Charles T., and Tzounopoulos, Thanos

Abstract

Many excitatory synapses contain high levels of mobile zinc within glutamatergic vesicles. Although synaptic zinc and glutamate are coreleased, it is controversial whether zinc diffuses away from the release site or whether it remains bound to presynaptic membranes or proteins after its release. To study zinc transmission and quantify zinc levels, we required a high-affinity rapid zinc chelator as well as an extracellular ratiometric fluorescent zinc sensor. We demonstrate that tricine, considered a preferred chelator for studying the role of synaptic zinc, is unable to efficiently prevent zinc from binding low-nanomolar zinc-binding sites, such as the high-affinity zinc-binding site found in NMDA receptors (NMDARs). Here, we used ZX1, which has a 1 nM zinc dissociation constant and second-order rate constant for binding zinc that is 200-fold higher than those for tricine and CaEDTA. We find that synaptic zinc is phasically released during action potentials. In response to short trains of presynaptic stimulation, synaptic zinc diffuses beyond the synaptic cleft where it inhibits extrasynaptic NMDARs. During higher rates of presynaptic stimulation, released glutamate activates additional extrasynaptic NMDARs that are not reached by synaptically released zinc, but which are inhibited by ambient, tonic levels of nonsynaptic zinc. By performing a ratiometric evaluation of extracellular zinc levels in the dorsal cochlear nucleus, we determined the tonic zinc levels to be low nanomolar. These results demonstrate a physiological role for endogenous synaptic as well as tonic zinc in inhibiting extrasynaptic NMDARs and thereby fine tuning neuronal excitability and signaling., National Institutes of Health (U.S.) (Grant R01-GM065519)

Published
2016

48. Reaction-based fluorescent sensor for investigating mobile Zn[superscript 2+] in mitochondria of healthy versus cancerous prostate cells

Author

Massachusetts Institute of Technology. Department of Chemistry, Chyan, Wen, Zhang, Daniel Y., Lippard, Stephen J., Radford, Robert J., Massachusetts Institute of Technology. Department of Chemistry, Chyan, Wen, Zhang, Daniel Y., Lippard, Stephen J., and Radford, Robert J.

Abstract

Chelatable, mobile forms of divalent zinc, Zn(II), play essential signaling roles in mammalian biology. A complex network of zinc import and transport proteins has evolved to control zinc concentration and distribution on a subcellular level. Understanding the action of mobile zinc requires tools that can detect changes in Zn(II) concentrations at discrete cellular locales. We present here a zinc-responsive, reaction-based, targetable probe based on the diacetyled form of Zinpyr-1. The compound, (6-amidoethyl)triphenylphosphonium Zinpyr-1 diacetate (DA-ZP1-TPP), is essentially nonfluorescent in the metal-free state; however, exposure to Zn(II) triggers metal-mediated hydrolysis of the acetyl groups to afford a large, rapid, and zinc-induced fluorescence response. DA-ZP1-TPP is insensitive to intracellular esterases over a 2-h period and is impervious to proton-induced turn-on. A TPP unit is appended for targeting mitochondria, as demonstrated by live cell fluorescence imaging studies. The practical utility of DA-ZP1-TPP is demonstrated by experiments revealing that, in contrast to healthy epithelial prostate cells, tumorigenic cells are unable to accumulate mobile zinc within their mitochondria., National Institute of General Medical Sciences (U.S.) (Grant GM065519), Massachusetts Institute of Technology. Undergraduate Research Opportunities Program

Published
2014

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