We will explore subcellular RNA localization and mechanisms of how RNA travels by using spatial technologies and a new software package we developed called Bento.

Understanding how the human brain perceives odorant and how the organization of our olfactory system varies from model systems requires functional measurements, connectivity, and spatial molecular expression. In this talk, I will discuss new scalable 3D imaging and analysis methods to generate highly multiplexed molecular mapping of human tissue, including the olfactory bulb. Using these approaches, we are working towards building a spatial molecular and cell atlas of the olfactory bulb.

Fibroblasts are structural cells that regulate tissue architecture, support homeostasis of tissue-resident cells, and play pivotal roles in fibrosis, cancer, autoimmunity, and wound healing. We apply multi-modal single-cell and spatial methods to identify and characterize fibroblast phenotypes across healthy tissues and disease indications. Our integrative analyses of fibroblasts represent an effort into implementing sophisticated single-cell methods toward the discovery of novel fundamental biology which will yield clinical dividends.

The ability to accurately assess cellular compositions and spatial organization of the tumor microenvironment are critical for development of improved cancer therapeutic strategies. New developments in single-cell sequencing and spatial transcriptomics that are compatible with fixed tissues are enabling powerful new study designs. Here, I will describe our progress in benchmarking these approaches and I will talk about how we are taking advantage of these new fixation-based methods to facilitate studies that require information about the detailed cellular architectures of human cancers.

The cellular architecture and immune composition of a tumor have a major impact on cancer outcome. We developed Perturb-map, a platform for functional genomics within a tissue at single-cell resolution with spatial architecture preserved. We used Perturb-map to knock out dozens of genes in parallel in preclinical cancer models and simultaneously assess how each gene influences tumor growth, histopathology and immune composition of the tumor microenvironment.

Potency assays are representative of the drug’s mechanism of action (MOA) and are designed to verify consistent biological activity. Many modern oncology drugs are designed to support and enhance the body’s defenses and are aimed to act specifically at the tumor. The direct (micro) environment of the tumor, therefore, typically encircles the key elements of the drug MOA which need to be represented in potency assays.