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!

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!).

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!

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.

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.

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.

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.

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…

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.

Thanks to @timofran1 @Pasca_Lab @UMICHpancreas for a great group to work with and folks for visiting the poster.

Same place as me…

@UmichCancBio retreat - getting great schooling by @AshaniTW on aging and tumor microenvironment WITH a cameo by @ednacukierman @CukiermanLab.