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

Lincoln Lab

Lincoln Lab photo 4-6-17

Lincoln Lab members (from left to right): Punashi Dutta, PhD; Donika Gallina, PhD; Emily Nordquist, BS; Caleb Colvin; Laureen Haack; Kaithlyn Thatcher, BS; Tori Horne; Bailey Dye, BS; and Joy Lincoln, PhD

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. More specifically, we are interested in examining the etiology of heart valve disease and examining parallels between valve development, and pathogenesis and regeneration of adult valves.

The formation of heart valves is a complex process involving multiple molecular pathways that modulate growth and morphogenesis of delicate, and highly organized leaflets. Alterations in these genetic networks during valvulogenesis frequently lead to congenital valve defects present at birth, including bicuspid aortic valve in 1-2% of the population. In addition to developmental defects, valve disease can be acquired and complications such as myxomatous degeneration and calcification are thought to arise from age-related ‘wear-and-tear’.

Despite the clinical significance, the regulatory pathways required for normal heart valve development and adult maintenance are largely unknown, and therefore we are unable to explain the etiology of congenital and acquired valve defects. To address this, my laboratory has established sophisticated tools to examine the molecular regulation of these processes in elegant model systems. Our long-term goal is to define the pathophysiology of heart valve disease and utilize these findings to develop alternative therapeutic strategies beyond surgical intervention.

Examples of our research

To see a full list of publications from our lab, please visit this PubMed link.

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

 

 

Immunostaining against Type Va1 Collagen highlights the atrioventricular valve structures (green) in the embryonic heart


 

 

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.

 

 

 

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.

Lincoln Lab myxomatous image

 

 

This Pentachrome-stained image shows an abnormal abundance of proteoglycans (blue) in myxomatous valves from mice lacking the gene, Filamin A.

 

>> Contact us to learn about available research opportunities.

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