Professor, Pediatrics; Feinberg School of Medicine
Tumor Invasion, Metastasis & Angiogenesis
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Our laboratory has spent the past 15 years seeking to understand the mechanisms of fibrosis that occur in chronic, progressive kidney disease. We have been studying the role of transforming growth factor (TGF-beta) because it has been associated with a number of kidney diseases. However, the classically described TGF-beta/Smad signaling pathway is too simple to account for the multiple, sometimes contradictory effects of TGF-beta on cell function. Therefore, we have sought to understand how cell phenotype and the molecular signature of a cell determine whether TGF- signaling leads to fibrosis. We have identified a number of non-canonical signaling pathways that interact with classical Smad signaling, including phosphatidylyinositide-3-kinase, ERK MAP kinase and hypoxia-inducible factors. We have begun to establish a hierarchy among these pathways and are studying the manipulation of these pathways in vitro and in mouse models in an effort to translate our basic findings into therapeutic approaches to halting or preventing the progression of kidney disease.