Faculty

Professional Experience

Lab Overview

My laboratory focuses on embryonic heart development. In particular, we are interested in the molecular and cellular regulation of heart valve formation, and use chicken and mouse systems to study mechanisms of valvulogenesis and adult valve disease in vitro and in vivo.

The mature valve leaflets and supporting chordae tendineae are composed of highly organized extracellular matrix (ECM) and cell lineages within the valve structures. The valve leaflet is composed of stratified matrices of collagens, proteoglycans and elastin, and lineages within the leaflet express genes associated with cartilaginous cell types. In contrast, chordae tendineae are composed of parallel bundles of elastin and collagen fibers, and express markers associated with tendon lineages. We have shown that during embryogenesis, these diverse valve structures are derived from undifferentiated mesenchyme cells of the endocardial cushion (Figure 1). However, the regulatory mechanisms required for valve precursor cell remodeling and formation of organized valve structures are poorly understood, but may be important in valve disease associated with aberrations in ECM composition and distribution.

Figure 1. Mesenchyme cells of the endocardial cushion (EC) (blue) undergo remodeling and give rise to diverse structures of the valve leaflets and chordae tendineae. The mature valve structures are composed of highly organized stratified ECM and cell lineages.

Therefore, our goals are to understand the molecular and cellular mechanisms that regulate valve leaflet and chordae tendineae formation from undifferentiated valve precursor cells. To determine this, we have employed an in vitro system to examine valve precursor cell lineage rem odeling in an environment where regulatory signals that control heart valve development can be manipulated. In addition, we are able to use mouse models to examine the effects of manipulated gene function on valve morphogenesis and function. These studies aim to identify genes required for normal valve development and provide insights into mechanisms of valve disease.

Lincoln Lab

(Left to Right): Marianna Porto PhD, Ge Tao BS, James Kotick BS, Joy Lincoln PhD (PI), Jacqueline Peacock BS, Agata Levay MS, Derek Rosenzweig PhD.

Meet the Lincoln Lab members

Selected Publications

Levay, A.K., Peacock, J.D., Lu Y., Hinton Jr., Koch, M., R.B., Kadler, K.E., Lincoln, J. Scleraxis is required for cell lineage differentiation and extracellular matrix remodeling during murine heart valve formation in vivo. In Press, Circulation Research, 2008.

Peacock, J.D., Lu, Y., Kadler, K.E., and Lincoln, J. Temporal and Spatial expression of collagens during murine atrioventricular heart valve development and maintenance. 2008 Sep 24;237(10):3051-3058. [Epub ahead of print].

Lincoln J., Kist, R., Scherer, G. Yutzey, K.E. Sox9 is required for valve precursor cell expansion and extracellular matrix organization during mouse heart valve development. Developmental Biology 305(1):120-32, 2007.

Hinton Jr., R.B*., Lincoln, J*., Deutsch, G., Osinska, H., Benson, W., Yutzey, K.E. Extracellular matrix remodeling and organization in developing and diseased aortic valves. Circulation Research 98(11):1431-8, 2006 . *Both authors contributed equally. Front cover article

Lincoln J., Florer, J.B., Deutsch, G.H., Wenstrup, R.J., Yutzey, K.E. ColVa1 and ColXIa1 are required for myocardial morphogenesis and heart valve development. Developmental Dynamics 235(12);3295-3305, 2006.

Lincoln J., Lange, A.L., Yutzey, K.E. “Hearts and Bones”: Shared regulatory mechanisms in heart valve, cartilage, tendon and bone. Review article. Developmental Biology 294; 292-302, 2006

Lincoln J., Alfieri, C.M., Yutzey, K.E. BMP and FGF regulatory pathways control cartilage- and tendon-like cell lineage differentiation of heart valve precursor cells. Developmental Biology 292;290-302, 2006.

Lincoln J., Alfieri, C.M., Yutzey, K.E. Development of heart valve leaflets and supporting apparatus in chicken and mouse embryos. Developmental Dynamics 229 (4), 2004. Front cover article.

 
Research Grants and Awards

Current Support

NIH R01 (HL091878)
08/01/2008 - 07/31/2013
PI: Joy Lincoln

Florida Biomedical Research Programs, James & Esther King Award (07KN-07)
07/01/2007 - 06/30/2010
PI: Joy Lincoln

Completed Awards

American Heart Association Scientist Development Grant (National)
07/01/2007 - 06/30/2011 (Inactivated due to scientific overlap)
PI: Joy Lincoln           

Stop Heart Disease Researcher of the Year Award (Florida Heart Research Institute) 2007