Richard N. Mitchell
Department of Pathology and Health Sciences and Technology
Brigham and Women's Hospital
77 Avenue Louis Pasteur, NRB 730D
Boston MA 02115
Lab Members: 1 postdoctoral fellow
The laboratory focuses on understanding the mechanisms of acute and chronic rejection in solid-organ allografts, and more broadly examining the interactions of inflammatory cells with vessel walls. These processes have direct relevance not only to transplantation, but also to in-stent restenosis, vein graft intimal hyperplasia, and atherosclerosis. In vivo murine aortic and cardiac allografts constitute a significant portion of the research, with patterned co-cultures and nanotechnology being increasingly used to model the interactions of innate and adaptive immune elements with endothelial or smooth muscle cells. Monoclonal antibody blockade and/or targeted deletions or knock-downs of various cytokines, chemokines, or their receptors permit examination of the roles of selected mediators and costimulatory molecules. Potential therapeutic strategies are also being formally tested in the various models. This work has shown the critical role of interferon-g in driving allograft arteriopathy and of interleukin-4 in inducing aneurysms. We have also demonstrated the contribution of circulating bone marrow-derived precursor cells to the process of vascular intimal hyperplasia.
Shimizu K, Sugiyama S, Aikawa M, Fukumoto Y, Rabkin E, Libby P, Mitchell RN. Host bone marrow cells are a source of donor intimal smooth muscle-like cells in murine aortic transplant arteriopathy. Nature Med. 2001; 7:738-741
Shimizu K, Aikawa M, Takayama K, Libby P, Mitchell RN. Direct anti-inflammatory mechanisms contribute to attenuation of experimental allograft arteriosclerosis by statins. Circulation 2003; 108:2113-2120
Shimizu K, Shichiri M, Libby P, Lee RT, Mitchell RN. Th2-predominant inflammation and blockade of IFN-gamma signaling induce aneurysms in allografted aortas. J Clin Invest. 2004;114:300-8
Mitchell RN. Graft Vascular Disease: Immune Response Meets the Vessel Wall. Annu Rev Pathol. 2009; 4:19-47.
For a complete listing of publications click here.
Last Update: 7/26/2012