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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.

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Concept Acetylcysteine
Concept Adenosine
Concept Antibiotics, Antineoplastic
Concept Antigens, Surface
Concept Antimetabolites, Antineoplastic
Concept Base Sequence
Concept Blood Group Antigens
Concept Calcium-Binding Proteins
Concept DNA-Binding Proteins
Concept Doxorubicin
Concept Enhancer Elements, Genetic
Concept Fibroblast Growth Factors
Concept Fluorouracil
Concept Heat-Shock Proteins
Concept Insulin-Like Growth Factor II
Concept Introns
Concept Nerve Tissue Proteins
Concept Nuclear Proteins
Concept Phosphoproteins
Concept Receptors, Transferrin
Concept Retinoids
Concept RNA, Messenger
Concept RNA, Ribosomal
Concept Sphingosine
Concept Transcription Factors
Concept Trans-Activators
Concept Antigens, CD
Concept Cadherins
Concept Tumor Suppressor Protein p53
Concept Transforming Growth Factor beta
Concept Fibroblast Growth Factor 1
Concept NF-kappa B
Concept RNA-Binding Proteins
Concept Reactive Oxygen Species
Concept Receptor, IGF Type 1
Concept Phosphotransferases (Alcohol Group Acceptor)
Concept DNA Primers
Concept Homeodomain Proteins
Concept Gene Expression Regulation, Developmental
Concept Cell Cycle Proteins
Concept Drug Resistance, Neoplasm
Concept Proto-Oncogene Proteins c-kit
Concept Stem Cell Factor
Concept Bone Morphogenetic Proteins
Concept Receptors, CXCR4
Concept Phosphatidylinositol 3-Kinases
Concept Sirolimus
Concept Activated-Leukocyte Cell Adhesion Molecule
Concept MicroRNAs
Concept Intercellular Signaling Peptides and Proteins
Concept Ubiquitin-Protein Ligases
Concept F-Box Proteins
Concept Proto-Oncogene Proteins c-akt
Concept PTEN Phosphohydrolase
Concept Wnt Proteins
Concept beta Catenin
Concept Receptor, Fibroblast Growth Factor, Type 1
Concept Basic Helix-Loop-Helix Transcription Factors
Concept Smad5 Protein
Concept Hedgehog Proteins
Concept Bone Morphogenetic Protein 4
Concept TOR Serine-Threonine Kinases
Concept RNA, Long Noncoding
Concept Prolyl Hydroxylases
Academic Article Maternal imprinting at the H19-Igf2 locus maintains adult haematopoietic stem cell quiescence.
Grant Overcoming therapeutic resistance by repurposing a classic chemotherapeutic drug as a targeted therapy to reactivate anti-cancer immunity
Grant Harnessing the Immune System to Fight Pediatric Cancer: Discovering Novel Inducers of Immunogenic Cell Death
Academic Article Overcoming Wnt-ß-catenin dependent anticancer therapy resistance in leukaemia stem cells.
Academic Article Overcoming resistance to immunotherapy by teaching old drugs new tricks.
Grant Harnessing anti-cancer immunity to vaccinate against treatment failure and relapse

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