Duffield, Jeremy

My laboratory has two major focuses. Firstly on the role of macrophage cells of the innate immune system in regulating tissue injury and regeneration. Secondly the function of mural cells of capillaries, known as pericytes, in microvascular repair in response to injury.

In animal models of sterile tissue injury similar to common human diseases we have discovered that macrophages play pivotal roles in directing tissue repair and stimulating organ regeneration. However if inappropriately activated by molecules released from damaged tissues, macrophages instead promote injury and drive tissue scarring. We have identified key pathways that regulate macrophage activation in sterile tissue injury including signaling via Fc gamma receptors, and important effector pathways that macrophages use to stimulate repair such as Wnt signaling pathway. Our goal is to modulate macrophage functions in vivo or stimulate regenerative pathways currently used by macrophages.

We recently described a population of cells known as pericytes in the microvasculature of the kidney. Pericytes are discrete cells that are partially embedded in capillary walls and are known to provide structural functions. Recent studies of pericytes in the brain and in cancer have identified potent angiogenic and vascular stabilizing functions that are vital to survival. We have discovered that in response to injury pericytes detach from capillaries and migrate away, differentiating into scar forming myofibroblasts. The consequence of migration and detachment is tissue fibrosis, but also unstable capillaries that may die. Our goal is to understand the molecular signaling pathways that govern pericyte-endothelial crosstalk.