Linking signal input, cell state, and spatial context to inflammatory responses.

Signal integration is central to a causal understanding of appropriately scaled inflammatory responses. Here, we discuss recent progress in our understanding of the stimulus-response linkages downstream of pro-inflammatory inputs, with special attention to (1) the impact of cell state on the specificity of evoked gene expression and (2) the critical role of the spatial context of stimulus exposure. Advances in these directions are emerging from new tools for inferring cell-cell interactions and the activities of cytokines and transcription factors in complex microenvironments, enabling analysis of signal integration in tissue settings.

In vivo CAR T-cell generation in nonhuman primates using lentiviral vectors displaying a multidomain fusion ligand.

Chimeric antigen receptor (CAR) T-cell therapies have demonstrated transformative efficacy in treating B-cell malignancies. However, high costs and manufacturing complexities hinder their widespread use. To overcome these hurdles, we have developed the VivoVec platform, a lentiviral vector capable of generating CAR T cells in vivo.

Post-translational modification-centric base editor screens to assess phosphorylation site functionality in high throughput.

Signaling pathways that drive gene expression are typically depicted as having a dozen or so landmark phosphorylation and transcriptional events. In reality, thousands of dynamic post-translational modifications (PTMs) orchestrate nearly every cellular function, and we lack technologies to find causal links between these vast biochemical pathways and genetic circuits at scale. Here we describe the high-throughput, functional assessment of phosphorylation sites through the development of PTM-centric base editing coupled to phenotypic screens, directed by temporally resolved phosphoproteomics.