135891 event 1340018764 1475891947 <![CDATA[Bioengineering Seminar Series]]> "Pathogenesis of Pulmonary Fibrosis: The Fibroblast in Focus"

James Hagood, MD
Chief of the Division of Respiratory Medicine
University of California San Diego School of Medicine

The lung develops from a simple epithelial tubular structure to a complex, vascular, high-surface-area gas exchange organ with diverse cellular phenotypes and a rich host defense program. The lung must respond to a variety of insults with rapid and efficient repair. If the repair process is excessive or prolonged, the result is fibrosis: excessive matrix deposition, structural distortion and major alteration in cellular phenotypes. In the case of idiopathic pulmonary fibrosis (IPF), this proceeds relentlessly, resulting in organ transplantation or death, with no effective therapy. Regardless of the initiating insult or the variety of early cellular and molecular derangements, a final common pathway for all fibrotic disorders is the emergence of the myofibroblast, a proliferative, apoptosis-resistant phenotype which becomes the “architect of destruction,” producing abnormal and excessive matrix, and contracting and distorting normal tissue. Our overarching goal is to understand mechanisms of lung myofibroblast differentiation in order to develop interventions to halt or reverse fibrogenesis. In order to meet this goal, we have leveraged the regulation and function of Thy-1, a glycophosphatidylinositol (GPI)-linked cell surface glycoprotein that dramatically modulates the myofibroblastic phenotype. Thy-1 in multiple cell and tissue contexts regulates cell adhesion, migration, and signaling regulating cytoskeletal arrangement and cell shape. In IPF, Thy-1 is silenced in lesional myofibroblasts, and restoration of Thy-1 expression in vitro reverses the myofibroblast phenotype. The current principal projects in our lab are: regulation of expression of Thy-1  by transcriptional silencing and shedding; understanding epigenomic alterations in lung development and fibrogenesis; exploring mechanisms of Thy-1 signaling regulating myofibroblastic adhesion, migration, differentiation and survival; and testing of Thy-1 and other antifibrotic therapies in animal models.

 

]]> The Bioengineering Seminar Series is a joint seminar series between IBB and the BME department. Seminars are held on Tuesdays or Thursdays between 11am-12pm in IBB room 1128 unless otherwise indicated.

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136561 image <![CDATA[James Hagood, MD - University of California San Diego]]> 194824 image/jpeg 141991 image <![CDATA[Bioengineering Seminar Series]]> 194960 image/png Thomas Barker, PhD, faculty host

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