Sylvia Evans

Affiliation: UCSD SOM

Associate Adjunct Professor of Medicine

Biography

Sylvia Evans did her PhD in Biochemistry at the University of British Columbia in bacterial genetics, and then came to the Salk Institute in La Jolla to do a postdoctoral fellowship with Steve Heinemann and Jim Patrick, studying the regulation of acetylcholine receptor genes at the neuromuscular junction in mouse. Sylvia has been on faculty at UCSD since 1991, where her research has focused on heart development and congenital heart disease, utilizing both frog and mouse as model systems.

Research Summary

The focus of our lab is to understand heart development from a number of different perspectives. A basic understanding of heart development is key toward understanding congenital heart disease. For adult heart disease, potential stem cell therapies will be facilitated by understanding the steps required to generate a cardiac cell from a stem cell.

Building a functioning heart requires the specification and interaction of a number of cell ineages of distinct function, including myocardial cells (either ventricular or atrial), endocardial cells (the endothelium, or lining of the heart), cardiac fibroblasts (support cells which provide extracellular matrix and growth factors), and conduction system lineages (the electrical wiring of the heart). Our lab is trying to understand the stepwise process by which mesodermal precursors become committed to cardiac progenitors, and then specified to become distinct lineages within the heart.

We are studying a number of transcription factors and growth factor pathways which are involved in this process, utilizing the mouse as a model system. We have created a number of mouse mutants which are defective in specific aspects of heart development. Some of these mutants mimic congenital heart defects seen in human patients. Characterization of these mutants is giving us insight into mechanisms of cardiac programming, the nature of cardiac progenitor/stem cells, and pathways involved in congenital heart disease.

An example of one of these mouse mutants is a mouse which carries a mutation in a LIM- homeodomain transcription factor. Homozygous mutants die embryonically at ED9.5 due to cardiac failure. The hearts of these mutants are missing entire segments of the heart (see Figure). Analysis has demonstrated that this transcription factor is a marker for a novel population of undifferentiated cardiac progenitor cells, and is also required for those progenitors to contribute to the heart. We are currently investigating the role this transcription factor might play in the formation of cardiac progenitor cells, or in the formation of cardiogenic stem cells. We are also exploring the possibility that human mutations in this gene result in congenital heart disease.

Figure legend: Scanning electron micrographs of wildtype (+/+) and mutant (-/-) mouse embryos at ED8.5 (A,C) and ED9.0 (B,D) of development. Segments of the heart are labelled: OT=outflow tract; RV=right ventricle; LV=left ventricle; A/V=atrial-ventricular junction; A=atria. In the mutants, whole segments of the heart are missing.

References

References From PubMed (NCBI)