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Search Results to John M. Perry

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research overview Dr. Perry's studies stem cells, cancer, immunology, and experimental therapeutics. While these seem like disparate fields, the lab has found surprising connections between them. Regarding stem cells, they study how normal blood-forming (hematopoietic) stem cells expand by making more of themselves, a process called self-renewal. They found that self-renewal was guided by the simultaneous activation of two genetic signaling pathways, Wnt/beta-catenin and PI3K/Akt. Pharmacological activation of these pathways drives the expansion of HSCs in culture, which are expected to be useful for therapy. In studying self-renewal, they made a mouse model that permanently activated the genetic pathways mentioned above by mutation. This resulted in the development of leukemia stem cells (LSCs), which are resistant to therapy and cause relapse. Since LSCs are particularly reliant on the interaction between Akt and beta-catenin, they did a high-throughput drug screen to discover inhibitors of this interaction. Surprisingly, a long-used chemotherapy drug, doxorubicin, would inhibit this interaction at very low doses. So, they repurposed doxorubicin as a targeted therapy against LSCs rather than a broadly toxic drug. By investigating the mechanism underlying doxorubicin's ability to target LSCs, they found that low-dose but not high-dose doxorubicin activated anti-cancer immunity. They are currently studying the details of this process and how they might 'immunize' pediatric patients against cancer relapse.

One or more keywords matched the following items that are connected to Perry, John

Item TypeName
Concept Mouse Embryonic Stem Cells
Concept Mice, Inbred C57BL
Concept Mice, Inbred DBA
Concept Mice, Mutant Strains
Concept Mice, Nude
Concept Mice, Transgenic
Concept Mice, Knockout
Concept Mice
Academic Article FGF signaling facilitates postinjury recovery of mouse hematopoietic system.
Academic Article Retinoid-Sensitive Epigenetic Regulation of the Hoxb Cluster Maintains Normal Hematopoiesis and Inhibits Leukemogenesis.
Academic Article BMP4 and Madh5 regulate the erythroid response to acute anemia.
Academic Article Maintenance of the BMP4-dependent stress erythropoiesis pathway in the murine spleen requires hedgehog signaling.
Academic Article MicroRNA programs in normal and aberrant stem and progenitor cells.
Academic Article Cooperation between both Wnt/{beta}-catenin and PTEN/PI3K/Akt signaling promotes primitive hematopoietic stem cell self-renewal and expansion.
Academic Article To be or not to be a stem cell: dissection of cellular and molecular components of haematopoietic stem cell niches.
Academic Article Isolation and characterization of intestinal stem cells based on surface marker combinations and colony-formation assay.
Academic Article Maternal imprinting at the H19-Igf2 locus maintains adult haematopoietic stem cell quiescence.
Academic Article Megakaryocytes maintain homeostatic quiescence and promote post-injury regeneration of hematopoietic stem cells.
Academic Article The Dlk1-Gtl2 Locus Preserves LT-HSC Function by Inhibiting the PI3K-mTOR Pathway to Restrict Mitochondrial Metabolism.
Academic Article Ribosomal DNA copy number loss and sequence variation in cancer.
Academic Article Suppression of m6A reader Ythdf2 promotes hematopoietic stem cell expansion.
Academic Article BMP4, SCF, and hypoxia cooperatively regulate the expansion of murine stress erythroid progenitors.
Academic Article Disrupting the stem cell niche: good seeds in bad soil.
Academic Article An intronic sequence mutated in flexed-tail mice regulates splicing of Smad5.
Academic Article N-cadherin expression level distinguishes reserved versus primed states of hematopoietic stem cells.
Academic Article Functional assays for hematopoietic stem cell self-renewal.
Grant Overcoming therapeutic resistance by repurposing a classic chemotherapeutic drug as a targeted therapy to reactivate anti-cancer immunity
Academic Article Overcoming Wnt-ß-catenin dependent anticancer therapy resistance in leukaemia stem cells.
Academic Article ß-Catenin and Associated Proteins Regulate Lineage Differentiation in Ground State Mouse Embryonic Stem Cells.
Grant Harnessing anti-cancer immunity to vaccinate against treatment failure and relapse
Academic Article Human Peripheral Blood Mononucleocyte Derived Myeloid Committed Progenitor Cells Mitigate H-ARS by Exosomal Paracrine Signal.

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