Joy Lincoln Lab :: The Research Institute at Nationwide Children's Hospital, Columbus, Ohio

Lincoln Lab



From L to R: Matthew Vandekopple, Lindsey Miller, Damien Barnette,
Danielle Huk, Blair Austin and Joy Lincoln

Research in the Lincoln Lab is focused on understanding the molecular mechanisms that regulate normal heart formation in the embryo and identifying developmental origins of adult cardiovascular disease. Development of the heart is a complex process involving multiple molecular pathways that modulate cardiac morphogenesis. Alterations in these genetic networks during embryogenesis frequently lead to structural cardiac defects, malfunction and congenital heart disease (CHD) in approximately 1% of all live births. Despite the clinical significance, the regulatory pathways required for heart formation, and the genetic contributions of CHD are largely unknown. Understanding the structure-function relationship of genes important during embryonic cardiogenesis will provide insights into genetic causes of CHD associated with structural defects and dysfunction. To understand this, my laboratory has established sophisticated in vivo tools to manipulate target gene function during cardiogenesis and examine heart structure and function in adult mutant mice. In addition, we have developed elegant in vitro tools that allow us to manipulate signaling pathways in primary cardiac cells.

Examples of our research

To view a full list of publications from our lab, please visit Joy Lincoln's bio page.

An active area of interest in our lab is focused on understanding the molecular and cellular processes required for development of heart valve structures.

 

 

 



Mature heart valves are composed of three stratified layers of specialized extracellular matrix, interspersed with valve interstitial cells, and surrounded by a single layer of valve endothelial cells. This highly organized structure is required for all the necessary biomechanical properties of the valves and must be maintained throughout life.

One of our areas of interest is focused on defining how organized valve structures form during embryogenesis, and how they are maintained after birth.

This is an image of a sheep aortic valve stained with Pentachrome to reveal the stratified layers of extracellular matrix.

 

 

 

 


 

Valve disease affects almost 5% of the human population and affected valves are characterized by loss of extracellular matrix organization and changes in matrix composition that affect the biomechanical properties and function.

In calcified valves, ectopic bone-like matrix develops on one side of the valve leaflet that leads to stiffening and inadequate movement. One goal of our lab is to identify candidate genes that promote, and prevent pathological bone-like processes in the valves. One candidate gene that we have published on is the SRY transcription factor, Sox9.

The staining in red identifies Sox9 expression in the mature mitral valve leaflets. Valve endothelial cells are highlighted in green, and cell nuclei in blue.

 

 

 

 

In contrast to calcified valves, myxomatous valves are "floppy" and prolapse back into the adjacent atria, leading to regurgitation. Histologically, myxomatous valves have abnormal exess proteoglycan deposition and one area of interest is currently investigating the mechanisms underlying this pathological state.

This image shows proteoglycan secretion (red) from cultured valve interstitial cells (green).

 

 

 

 



Contact us to learn about available research opportunities at Joy.Lincoln@NationwideChildrens.org.
 

Nationwide Children's Hospital
700 Children's Drive Columbus, Ohio 43205 614.722.2000