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Your search keyword '"Dolores Hambardzumyan"' showing total 3 results
Start Over Author "Dolores Hambardzumyan" Journal cell reports
3 results on '"Dolores Hambardzumyan"'

1. Ly6Chi Monocytes Provide a Link between Antibiotic-Induced Changes in Gut Microbiota and Adult Hippocampal Neurogenesis

Author

Luisa Möhle, Daniele Mattei, Markus M. Heimesaat, Stefan Bereswill, André Fischer, Marie Alutis, Timothy French, Dolores Hambardzumyan, Polly Matzinger, Ildiko R. Dunay, and Susanne A. Wolf

Subjects
Biology (General), QH301-705.5
Abstract

Antibiotics, though remarkably useful, can also cause certain adverse effects. We detected that treatment of adult mice with antibiotics decreases hippocampal neurogenesis and memory retention. Reconstitution with normal gut flora (SPF) did not completely reverse the deficits in neurogenesis unless the mice also had access to a running wheel or received probiotics. In parallel to an increase in neurogenesis and memory retention, both SPF-reconstituted mice that ran and mice supplemented with probiotics exhibited higher numbers of Ly6Chi monocytes in the brain than antibiotic-treated mice. Elimination of Ly6Chi monocytes by antibody depletion or the use of knockout mice resulted in decreased neurogenesis, whereas adoptive transfer of Ly6Chi monocytes rescued neurogenesis after antibiotic treatment. We propose that the rescue of neurogenesis and behavior deficits in antibiotic-treated mice by exercise and probiotics is partially mediated by Ly6Chi monocytes.

Published
2016
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2. Protein kinase C

Author

Rajappa S, Kenchappa, Yi, Liu, Michael G, Argenziano, Matei A, Banu, Ann C, Mladek, Rita, West, Amanda, Luu, Alfredo, Quiñones-Hinojosa, Dolores, Hambardzumyan, Verline, Justilien, Michael, Leitges, Jann N, Sarkaria, Peter A, Sims, Peter, Canoll, Nicole R, Murray, Alan P, Fields, and Steven S, Rosenfeld

Subjects
Gene Expression Regulation, Neoplastic, Isoenzymes, Disease Models, Animal, Mice, Carcinogenesis, Cell Line, Tumor, Animals, Gene Expression, Humans, Oncogenes, Glioblastoma, Protein Kinase C, Signal Transduction
Abstract

We report that atypical protein kinase Cι (PKCι) is an oncogenic driver of glioblastoma (GBM). Deletion or inhibition of PKCι significantly impairs tumor growth and prolongs survival in murine GBM models. GBM cells expressing elevated PKCι signaling are sensitive to PKCι inhibitors, whereas those expressing low PKCι signaling exhibit active SRC signaling and sensitivity to SRC inhibitors. Resistance to the PKCι inhibitor auranofin is associated with activated SRC signaling and response to a SRC inhibitor, whereas resistance to a SRC inhibitor is associated with activated PKCι signaling and sensitivity to auranofin. Interestingly, PKCι- and SRC-dependent cells often co-exist in individual GBM tumors, and treatment of GBM-bearing mice with combined auranofin and SRC inhibitor prolongs survival beyond either drug alone. Thus, we identify PKCι and SRC signaling as distinct therapeutic vulnerabilities that are directly translatable into an improved treatment for GBM.

Published
2021

3. Protein kinase Cι and SRC signaling define reciprocally related subgroups of glioblastoma with distinct therapeutic vulnerabilities

Author

Rita West, Amanda Luu, Michael G. Argenziano, Matei A. Banu, Verline Justilien, Peter A. Sims, Alfredo Quinones-Hinojosa, Ann C. Mladek, Dolores Hambardzumyan, Yi Liu, Nicole R. Murray, Alan P. Fields, Steven S. Rosenfeld, Michael Leitges, Rajappa S. Kenchappa, Jann N. Sarkaria, and Peter Canoll

Subjects
Auranofin, Chemistry, Cancer research, Src inhibitor, medicine, Tumor growth, Protein kinase C iota, Protein kinase A, medicine.disease, General Biochemistry, Genetics and Molecular Biology, medicine.drug, Glioblastoma, Proto-oncogene tyrosine-protein kinase Src
Abstract

Summary We report that atypical protein kinase Cι (PKCι) is an oncogenic driver of glioblastoma (GBM). Deletion or inhibition of PKCι significantly impairs tumor growth and prolongs survival in murine GBM models. GBM cells expressing elevated PKCι signaling are sensitive to PKCι inhibitors, whereas those expressing low PKCι signaling exhibit active SRC signaling and sensitivity to SRC inhibitors. Resistance to the PKCι inhibitor auranofin is associated with activated SRC signaling and response to a SRC inhibitor, whereas resistance to a SRC inhibitor is associated with activated PKCι signaling and sensitivity to auranofin. Interestingly, PKCι- and SRC-dependent cells often co-exist in individual GBM tumors, and treatment of GBM-bearing mice with combined auranofin and SRC inhibitor prolongs survival beyond either drug alone. Thus, we identify PKCι and SRC signaling as distinct therapeutic vulnerabilities that are directly translatable into an improved treatment for GBM.

Published
2021
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