Faculty

SYLVIA M. EVANS

Professor of Pharmacology

School of Pharmacy and Pharmaceutical Sciences

TEL: 858-822-2452

email:syevans@ucsd.edu

Ph.D., University of British Columbia

Lab Website

Key Words: adult heart disease, heart development, congenital heart disease, cardiac lineages, stem cell

The focus of our lab is to define genetic pathways underlying heart development and to apply that understanding to both congenital and adult heart disease. A basic understanding of heart development is key toward understanding congenital heart disease. Pathophysiological remodelling which occurs during cardiac disease has been demonstrated to result in expression of developmental, rather than adult, gene programs. It is likely that an understanding of mechanisms which regulate these gene programs during development will also be applicable during pathophysiological remodelling. Recent data from a number of labs have suggested that repair of damaged myocardium may be enhanced by cell based therapies, based on the ability of donor cells to differentiate into myocardial cells. Insights into developmental pathways required for myocardial differentiation will allow for enhanced differentiation and integration of donor cells into recipient myocardium. Additionally, recent results from our lab and from others have demonstrated the presence of resident cardiogenic progenitor cells in adult heart which may provide a source for myocardial regeneration following injury. As for the case with skeletal muscle satellite cells, these cardiac progenitor cells may follow a developmental program during their differentiation in the context of adult heart.

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), proepicardial organ (will give rise to coronary vasculature) 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 have created a number of cre-expressing mouse models which will enable us to examine gene pathways required for specific cardiac lineages, including that of the proepicardial organ, cardiac fibroblasts, and the sino-atrial node. Another area of active interest to us is the formation of the coronary vasculature.

Selected Publications

Cai, C.L, Shi, Y., Pfaff, S., Chen, J., and Evans, SM. Isl1 Identifies a Cardiac Progenitor Population that Proliferates Prior to Differentiation and Contributes a Majority of Cells to the Heart. Developmental Cell. 5:878-889, 2003 (featured article)

Garcia Frigola, C., Shi, Y., and Evans SM. Expression of the hyperpolarization-activated cyclic nucleotide gated cation channel HCN4 during mouse heart development. Mechanisms of Development. 3: 777-783, 2003

Huang, C., Sheikh, F, , Hollander, M., Cai, C., Becker, D., Chu, P., Evans, SM, and Chen, J. Embryonic Atrial Function is Required for Cardiac Morphogenesis and Vasculogenesis. Development 130 (24):6111-9, 2003

Kondo RP, Anderson, RH, Kuperschmidt, S, Roden, DM, and Evans, SM. Development of the Cardiac Conduction System as Delineated by MinK-lacZ. J. Card. Electrophys. 14(4):383-391,2003