Mitchell Alan Olman, MA, MD
Lerner Research Institute,
9500 Euclid Avenue, Cleveland, Ohio 44195
Phone: (216) 445-6025
Our research is focused on the pathogenesis on the fatal and untreatable disorder of idiopathic pulmonary fibrosis. The general approach we adopt is to investigate pulmonary fibrosis at the molecular level, in cells and animal models, and to validate the newly-discovered pathways using patient samples. We focus on the fundamental biology of scar formation by fibroblasts and fibroblast-like cells.
Our recent work has focused on the processes of fibroblast migration and transdifferentiation. We have shown that a naturally occurring inhibitor of integrin-dependent signaling, focal adhesion kinase non-kinase (FRNK), can block TGF-beta –induced myofibroblast differentiation, and the development of pulmonary fibrosis in vivo. In ongoing work, we have also shown that the cell surface receptor for the fibrinolytic protease, urokinase, interacts with integrins in primary human lung fibroblasts thereby enhancing the integrin-dependent functions of fibroblast attachment and migration. Lastly, we have identified an ion channel that may control the process of myofibroblast differentiation.
At the bedside, we are privileged to co-author a NIH-sponsored, multicenter clinical trial of anticoagulants in idiopathic pulmonary fibrosis. This approach will hopefully lead to improved outcomes..
We study the disease idiopathic pulmonary fibrosis. Our work tries to understand the process of scarring in the lung with the goal of identifying new targets with which to treat this disease. We focus on fibroblasts, the cells that form the scar in the lung. We study how these fibroblasts become activated and thereby act as potent scar formers.
K White, Q Ding, B Moore, M Peters-Golden, L Ware, M Matthay and M.A. Olman.PGE2 mediates IL-1β-related fibroblast mitogenic effects in acute lung injury through differential utilization of prostanoid receptors. J Immunol 180 (1): 637-646; 2008
Q Ding, C Gladson, H Wu, H Haysaka and MA Olman. FAK-related non-kinase inhibits myofibroblast differentiation through differential MAPK activation in a FAK-dependent manner. J Biol Chem 2008; 283:26839-49
S Zhu, C Gladson, K White, Q Ding,J Stewart, Jr., T Jin, H Chapman, Jr, and M A. Olman. Urokinase receptor mediates lung fibroblast attachment andmigration towards provisional matrix proteins through interactions with multiple integrins. Am J of Physiol:LCMP 2009; 297:L97-L108
In a new study published in Science Signaling, Cleveland Clinic researchers have identified a novel target for new therapies that may help to treat or prevent a host of fibrotic conditions, which contribute to nearly half of overall mortality in the United States.