Department of Biochemistry Bhussry Seminar Series Presents: José Ordovas-Montanes, Ph.D

Single-Cell to Tissue-Scale Inflammatory Memory

January 30th, 2024, 12-1 pm, Basic Science Building Room 341

The role of epithelial and stromal cells in driving inflammation, together with immune cells, is being increasingly appreciated. However, we currently lack tissue-scale frameworks to define and test how inflammation collectively impacts epithelial, stromal, and immune cells. This poses a fundamental challenge for understanding the cellular mechanisms that drive or sustain health and disease within, and across, barriers such as the skin, airway, and intestine. Our lab is addressing this challenge by quantifying and controlling how inflammation changes the ecology (i.e. function, structure and relationships between cells) of barrier tissues. Our central hypothesis is that inflammation is distributed and stored in multiple cell types, with the capacity to form tissue-level collective cellular networks.

Starting from our human single-cell RNA-sequencing (scRNA-seq) data collected from infectious and inflammatory diseases, we are developing quantitative approaches to define how static cellular ecosystems are arranged in barrier tissues. Recent human scRNA-seq work has focused on identifying the collective cellular networks that may influence disease trajectory in the nasal mucosa of patients with COVID-19, and in the terminal ileum of Crohn’s disease patients. These studies are informing time-series modeling of murine inflammatory models focused on Type 1/17 inflammation to understand how the same pressure applied to epithelial, stromal, and immune cell subsets shifts functional states and interactions in distinct barrier tissues. We anticipate to identify the gradual inflammatory transitions which maintain essential tissue functionality and critical “tipping points” in tissue state that compromise barrier functions.

Our group seeks to collaborate with the community towards understanding unique and general inflammatory mechanisms across tissues and species to improve human health.