Our laboratory is interested in defining the cellular pathways that regulate kidney epithelial development and repair and determining the effector proteins that mediate the changes that occur during tubule formation, injury and repair. We have found that macrophages are critical regulators of both initial injury and subsequent repair, and that cross-talk between macrophages and surviving tubular cells determines the macrophage expression profile that induces tubule repair. We have identified activation of the phosphoinositide 3-kinase and MAPK pathways as critical regulators of epithelial cell migration and morphogenesis during both development and repair.
Specialized Terms: Nephrology; Acute Kidney Injury; Physiology and integrative medical biology; Epithelial cell migration and morphogenesis; Epithelial cell adhesion; Migration; Branching tubulogenesis
The primary focus of our laboratory is to determine the mechanisms of renal tubule development, homeostasis and repair. When the kidney is injured following ischemia or toxin exposure, the remaining epithelial cells de-differentiate, spread over the denuded basement membrane, divide, and re-arrange themselves in a specific pattern to regenerate functional tubules. This process requires a complex array of events involving rearrangement of cell shape and regulation of cell-matrix and cell-cell interactions. By examining epithelial cell adhesion, migration, and branching tubulogenesis in response to growth factors such as Hepatocyte Growth Factor and chitin's 3-like 1, we are determining the intracellular signaling events critical for tubule formation during kidney development and following injury. We have focused these efforts on the role of activation of specific MAPK isoforms as well as the PI 3-kinase in the regulation of cell morphogenesis and cell-matrix interactions.
In addition, we are examining the role of the innate immune response to kidney injury and found that macrophages home to the injured kidney and initially promote apoptosis of sublethally injured tubular cells. Subsequent macrophage accumulation includes increasing numbers of alternatively activated macrophages that promote the survival and proliferation of the remaining tubular cells to effect tubule repair. We are currently expanding this work to study human acute kidney injury and have developed the use of Imaging Mass Cytometry in the human kidney.
Epithelial Cells; Kidney; Macrophages; Morphogenesis; Nephrology; Physiology