Publications by authors named "Helen I Gandler"

Pancreatic cancer is characterized by aberrant activity of oncogenic KRAS, which is mutated in 90% of pancreatic adenocarcinomas. Because KRAS itself is a challenging therapeutic target, we focused on understanding key signaling pathways driven by KRAS as a way to reveal dependencies that are amenable to therapeutic intervention. Analyses in primary human pancreatic cancers and model systems revealed that the receptor for the cytokine leukemia inhibitory factor (LIF) is downregulated by mutant KRAS.

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Malignant pleural mesothelioma (MPM) is an aggressive cancer defined by loss-of-function mutations with few therapeutic options. We examined the contribution of the transcription factor Signal transducer and activator of transcription 3 (STAT3) to cell growth and gene expression in preclinical models of MPM. STAT3 is activated in a variety of tumors and is thought to be required for the maintenance of cancer stem cells.

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Article Synopsis
  • Researchers found that the kinase IKBKE is more active in acute myeloid leukemia (AML) cells than in normal blood cells, suggesting it could be a potential treatment target.
  • * Inhibiting IKBKE or its related kinase TBK1 triggers cell death in AML cells and reduces their growth, especially in cells with an MYC oncogenic profile.
  • * The drug Momelotinib effectively blocks IKBKE/TBK1, lowering MYC levels and showing promising results in both laboratory and animal models for treating AML.
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The American lobster, Homarus americanus, is a model for investigating the neuromodulatory control of physiology and behavior. Prior studies have shown that multiple classes of chemicals serve as locally released/circulating neuromodulators/neurotransmitters in this species. Interestingly, while many neuroactive compounds are known from Homarus, little work has focused on identifying/characterizing the enzymes responsible for their biosynthesis, despite the fact that these enzymes are key components for regulating neuromodulation/neurotransmission.

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