BME Seminar Series: Dr. Joy Lincoln, Nationwide Children's Hospital Research Institute

"The role of Sox9 in the pathogenesis of calcific aortic valve disease"

Abstract

Calcific aortic valve disease (CAVD) is a prevalent disorder affecting up to 13% of the population. Its etiology is largely unknown and at present, the only treatment is effective surgical repair or replacement. The disease is characterized by differentiation of valve interstitial cells into an osteoblast-like lineage and appearance of calcific nodules on the surface of the valve leaflet. This is in contrast to healthy valve leaflets that exhibit a cartilage-like phenotype that provides the necessary biomechanical properties to allow for opening and closing during the cardiac cycle. My lab discovered that the transcription factor Sox9 is required in valve interstitial cells to promote and maintain healthy cartilaginous phenotypes and prevent bone-like calcification. Without Sox9, valves lose expression of chondrogenic markers and calcify and our new data suggests that nuclear shuttling of Sox9 plays a critical role in regulating this balance. Ongoing studies are utilizing nuclear export inhibitors to prevent, rescue and reverse calcification using in vitro that can be translated into in vivo models to examine therapeutic potential.

Dr. Lincoln completed her PhD in molecular biology at The University of Durham in the UK and her Post Doctoral training with Dr. Katherine Yutzey at Cincinnati Children’s Hospital Medical Center. She joined faculty at the University of Miami, Florida in 2006 and relocated to Nationwide Children’s Hospital in 2011 where she holds a Principal Investigator position in the Center of Cardiovascular Research and Tenured Associate Professor at The Ohio State University. Her lab is focused on defining the mechanisms that underlie congenital heart valve malformations and understanding the etiology of valve disease acquired after birth. Studies form her lab have made significant contributions to the field and identified critical signaling pathways that regulate cell fate determination of valve cell populations in development and disease. Dr. Lincoln served at Director of the Post Doctoral Training Office at The University of Miami and is the current Associate Director of Faculty Development at Nationwide Children’s Hospital.