Faculty

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 remodeling 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 Members: Agata Levay, Joy Lincoln, Jacqueline Peacock

Meet the Lincoln Lab members

Selected Recent Publications

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.

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.

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., 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.

Lako, M., Lindsay, S., Lincoln, J., Cairns, P.M., Armstrong, L., Hole, N. Charaterisation of Wnt gene expression during the differentiation of murine embryonic stem cells in vitro: role of Wnt3 in enhancing haematopoietic differentiation. Mechanisms of Development 103, 49-59 2001

Armstrong, L., Lako, M., Lincoln, J., Cairns, P.M., Hole, N. mTert expression correlates with telomerase activity during the differentiation of murine embryonic stem cells. Mechanisms of Development 97, 109-116, 2000

 
Research Grants and Awards

Lincoln, J: AHA Scientist Development Grant (National, 0735220N)
07/01/2007-06/30/2011
“Molecular and cellular regulation of heart valve cell lineage diversification and differentiation”.
Scleraxis regulation of heart valve precursor cells and adult valve maintenance

Lincoln J: Florida Biomedical Research Programs, James & Esther King (07KN-07)
07/01/2007-06/30/2010
“Molecular regulation of heart valve development and disease”.
Sox9 function in establishing and maintaining connective tissue homeostasis in embryonic and adult heart valves.

Peacock, J: NIH Training Program in Cardiovascular Signaling.

Professional Experience

BSc (Hons)-Biomedical Sciences, University of Durham, UK (1995-1998)

Ph.D-Molecular and Developmental Biology, University of Durham, UK (1998-2002)

Certificate in Teaching Higher Education, University of Durham, UK (1999)

Postdoctoral Research Fellowship, Cincinnati Children’s Hospital (2002-2006)

Assistant Professor, University of Miami (2006-Present)