SUMMARY
The research interests of our laboratory center on mechanisms of injury and adaptation in the kidney and in the vasculature in general, focusing on mechanisms related to oxidative stress. Within this area, special attention is directed to the inducible antioxidant enzyme, heme oxygenase-1 (HO-1), as an adaptive response that confers protection against injury to the kidney and vasculature. Mechanisms through which the cytoprotective effects of HO-1 may arise (for example, vasodilatory, anti-apoptotic, and anti-inflammatory actions) are explored, and the involvement of products of heme oxygenase activity (for example, carbon monoxide, bilirubin, and ferritin) in contributing to such cytoprotection is also examined. These studies are pursued in collaboration with the Vascular Molecular Biology Laboratory at Mayo, as are studies that examine the study of recombinant HO-1 to protect against vasospasm; the latter represents a component of the program project grant in the Molecular Medicine Program at Mayo devoted to the examination of gene therapy for vaso-occlusive disease.
Our laboratory also pursues the theme of injury and adaptation in the kidney and vasculature in sickle cell disease using, among others, approaches based on transgenic models of sickle cell disease. Specifically, in this disease process the role of oxidative stress as a determinant of such injury in the sickle milieu and the role of heme oxygenase-1 as a protective response are explored. These studies are part of the program project grant on the vascular biology of sickle cell disease centered at the University of Minnesota.
Finally, our laboratory collaborates with other initiatives at Mayo that explores signaling pathways that underlie the renal fibrogenic actions of TGF-beta 1.