Research in my lab focuses on elucidating mechanisms regulating tissue homeostasis and inflammation. Mammalian tissues are ecological communities of diverse cell types, including immune cells, stromal cells, neurons, endothelial cells and tissue parenchymal cells. We are interested in studying how immune cells communicate with their tissue neighbors and surrounding environment to maintain homeostatic states of a tissue ecosystem, and how dysregulation of cell-cell and cell-environment interactions may lead to inflammatory disorders We use bottom-up systems approach combined with computational modeling, chemical genetic engineering, high-throughout technologies and in vivo mouse models for an in-depth, quantitative and mechanistic understanding of immunity and tissue ecology. Our current interests include 1) identifying mechanisms of controlling the composition and organization of immune cells, 2) understanding how tissue microenvironment modulates immune functions as a potential strategy to control inflammation, 3) programming genetic and cellular circuits to control immune functions for treating inflammatory disorders and cancer.

Although immune cells are well-known for their mobility, it’s becoming clear that tissue resident immune cells, such as macrophages, are organized into unique spatial patterns within tissues. We are interested in uncovering cellular mechanisms that organize immune cells spatially and temporally, and how such organization dictates their homeostatic and inflammatory functions. In addition, appropriate numbers and ratios of different cell types are ensured throughout tissue development. Sustained changes in tissue composition often underlie pathological transition in inflammatory diseases. How is the compartment size of immune & non-immune cells maintained, regulated and altered at homeostasis and inflammatory conditions? We are also interested in identifying molecular and cellular principles defining tissue composition, with the goal of creating synthetic modules to control cell numbers and restore tissue homeostasis.

Immune cells are specialized into sensing infections and injuries. They also express diverse receptors that monitor tissue microenvironment, such pH, oxygen, osmolarity, pressure, etc. These variables are often impacted by inflammatory response, as a consequence of host defense mechanisms. A good example is extravasation. Recruitment of neutrophils and monocytes to the site of infection helps clear pathogens, at the cost of perturbing microenvironment variables. We are interested in dissecting how changes in tissue microenvironment modulate immune functions as a potential strategy to control inflammation.

Macrophages have recently gained attractions in immune engineering and cancer immunotherapy. They are present in almost all tissues and possess diverse functions. We are interested in engineering macrophages to control their population size, interaction partner, location, and response to given environmental cues, as cellular vehicles to treat inflammatory disorders, cancer and fibrotic disease.