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Invited talk 1

Harvard Medical School, U.S.A.

Dr. Zhou is a Principal Investigator and an Assistant Professor of Pediatrics at Boston Children’s Hospital and Harvard Medical School, and an Associate Member of the Broad Institute of MIT and Harvard. Xu earned his B.S. from Peking University, Ph.D. with Dr. Erin O’Shea at Harvard University, and postdoctoral training with Dr. Ruslan Medzhitov at Yale University School of Medicine. Since 2021, the Zhou Lab is interested in developing novel tools and concepts to study how immune cells communicate with their neighbors and surrounding environment to control tissue homeostasis and inflammation. Xu has received Jane Coffin Childs Postdoc fellowship, Kenneth Rainin Innovator award, Charles Hood Health award, Harold & Leila Y. Mather’s Foundation Research award among other recognitions. Xu serves on Harvard graduate recruitment committee, organizing committees for Early Career Immunology, Systems and quantitative biology, and Keystone meeting in Innate immunity.

Topic:  Bottom-up mechanistic understanding of tissue homeostasis and inflammation

Summary:  All individuals need to maintain homeostasis at cellular, tissue and organismal levels in order to survive. However, mechanisms that regulate and maintain tissue homeostasis and how their dysregulation leads to inflammatory disorders are currently poorly understood. In particular, we took a bottom-up approach to study the mechanisms that control the interactions between immune and stromal cells and between immune cells and their surrounding micro-environment. A hallmark of tissue homeostasis is to maintain the relative abundance of each cell type. Yet the mechanisms by which the abundance of a given cell type is sensed, regulated, and coordinated with the other cell types are not known. We established a two-cell circuit based on growth factor exchange between macrophages and fibroblasts, two common cell types in most mammalian tissues. This in vitro system exhibits many properties inherent to a complex but stable tissue, namely that the relative abundance of each cell type converges to a stable state even when the starting ratios of the two cells differ by more than 100-fold. This remarkable feature has enabled us to derive general principles that quantitatively control homeostasis among different types of cells. Our works discovered two ways of how the cross-talk regulates immune-stromal homeostasis: the mutual exchange of growth factors and physical association maintains relative population abundance over time, and environmental signals act on stromal cells to control the quantity of macrophages, both of which cannot be studied with each cell type alone. In addition, inflammatory response impact tissue homeostasis by altering tissue environment, such as pH, oxygen level or composition of cells. Immune cells, such as macrophages, constantly monitor tissue environment and maintain tissue homeostasis. We interrogated how changes in tissue environment feedback to modulate immune functions as a strategy to balance tissue protection and inflammatory pathology. Collectively, our works provide a generalizable framework to understand mechanisms of tissue homeostasis and inflammation.

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