Pancreatic cancer research, epigenetics, tumor immunology, tumor evolution, surgeons doing basic science, UM PanTErA, #NewPISlack, personal Twitter: @Fil_Bednar
University of Michigan
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In the end, not a “failure” at all but success in a different way. Thanks to my scientific mentors and “parents” – Marina Pasca di Magliano, Howard Crawford, to the great environment of our UMich pancreas group, and to my friend and colleague Chris Pin!
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Our work confirmed our observations, the Ptf1a-CreER system shows more transformation, more myeloid infiltration, and likely differential reprogramming of signaling pathways compared to the other two models. There are tantalizing hints of mechanism in the paper (READ IT!).
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Our team at #PancMidwestChicago! What a fantastic meeting including a spectacular northern lights show on a clear night! Thoroughly enjoyed it, gotta do it again!
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We confirm the role of myeloid-specific Notch signaling genetically by using a myeloid-specific inhibition of Notch signaling via the dominant negative MAML expression and an orthotopic tumor approach.
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We explore pharmacological Notch inhibition in the absence and presence of PD-1/PD-L1 inhibition using lines with varying immune response in orthotopic tumors. Notch inhibition leads to an improved cytotoxic T cell response but role of PD-1 depends on underlying T cell context.
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As others before, we also confirm that direct contact with tumor cells activates Notch signaling in vitro in bone-marrow derived macrophages. Synthesis of immunosuppressive cytokines is also inhibited by gamma secretase inhibitors in vitro.
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The reporter allows us to isolate TAMs and separate them based on levels of Notch signaling and characterize them. We find that Notch-signaling+ TAMs express more immunosuppressive cytokines.
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We used a fluorescent reporter to isolate cells with native levels of Notch signaling from the tumor microenvironment to further characterize them.
bmcdevbiol.biomedcentral.com…
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Using scRNA-seq and validation by immunofluorescence, we identify Notch signaling in multiple TME components including the myeloid cells, T cells, fibroblasts, and the endothelium in both human tissue and murine models of pancreatic cancer.
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Thanks to @timofran1 @Pasca_Lab @UMICHpancreas for a great group to work with and folks for visiting the poster.
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@UmichCancBio retreat - getting great schooling by @AshaniTW on aging and tumor microenvironment WITH a cameo by @ednacukierman @CukiermanLab.
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What happens, when one is drawing with chalk with kids, and an idea synthesizes in one’s head? You write it down, of course! Nothing novel here just restatement of Buenrostro et al. Cell 2018...
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(12/12) I have @LyssiotisLab to thank for this #tweetorial motivation! I hope I did it some justice to represent the hard work of all involved!
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(10/12) To clinch the story, we depleted Tregs while inhibiting CCR1 pharmacologically. This did not allow the myeloid influx after Treg depletion and restored a productive anti-neoplastic response with more recovery of the pancreatic tissue.
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(8/12) In addition, Treg depletion seemed to also push the helper T cell response to a Th2-like phenotype, which may be protumorigenic in other contexts.
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(3/12) We have previously found that removing all CD4+ T cells during early stages of pancreatic tumor growth allows cytotoxic T cells to eliminate early lesions with no tumors forming.
cancerimmunolres.aacrjournal…
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I am grateful to work with these talented folks in my little group and as part of the larger pancreatic cancer effort @UMRogelCancer. Time for a lab dinner and a little fun after!
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Anirban Maitra @MDAndersonNews
#AACRPanCa19
Nothing like an early detection talk starting with the ‘Princess Bride’...
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Eileen Carpenter, GI Fellow @UMRogelCancer @umichmedicine
Awesome job presenting multimodal analysis of human pancreatic cancers - huge collab, proud to contribute to this effort!
#AACRPanCa19
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Evening #1: #AACRPanCa19
1. Beautiful talk by @MaraShermanLab on fibroblasts in pancreatic tumor stroma. Can’t wait until this is published
2. Encyclopedic overview of tumor immunosuppression and how to break it by George Miller @nyulangone
Just a start to the wknd.
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Off we go! To Boston with @HCCvPDAC, Marina Pasca di Magliano, and @JiaqiShi for #AACRPanCa19! To for some pancreatic cancer science!
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