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. Currently, we are developing new genetic and functional genomic approaches to study cell-cell interactions between immune and stromal cells. Our long-term goal is to outline a cellular language that dictates the interactions between specific immune and stromal cell types across health and disease.
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 interested in identifying molecular and cellular principles defining tissue composition and driving the switch between alternative tissue states. Our future goal is to create 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. Current projects focus on understanding how changes in tissue microenvironment modulate immune functions, discovering new ways of how immune cells detect microenvironments, and creating tool kits to manipulate environmental variables as a potential strategy to control inflammation.
Programming immune functions
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.