Children's Hospital of Philadelphia 710A Abramson Research Building 34th and Civic Center Blvd. / 4399
(215) 590-0606

CVI Program Unit(s):
Cardiovascular Development / Congenital Heart Disease

CVI Research Description:
Role of Eomesodermin in cardiac development and mesoderm differentiation; new gene discovery in cardiac development and congenital heart disease.

Research Interests
T-box genes and TGF-beta signaling in mesoderm differentiation and cardiac development.

Key words: T-box, mesoderm, Xenopus, transcription factor, TGF-beta, cardiac.

Description of Research
I am a developmental biologist interested in the factors responsible for early heart formation in the developing embryo. Understanding these factors may lead to better treatments for cardiovascular disease. Another of my research interests involves analyzing the regulation of the promoter of a certain gene expressed in the heart. This could lead to novel molecular targets for drug intervention.

My colleagues and I have discovered, cloned and characterized an early TGF-beta response gene called Eomesodermin. This gene is one of the earliest markers of mesodermal cells in embryos, cells which give rise to heart and skeletal muscle. We have found that Eomesodermin is required very early in the process of forming these tissues. In our studies of heart development, we primarily employ early embryonic development in Xenopus laevis. We have also recently used mouse knockout technology to confirm and extend our earlier results.

Rotation Projects for 2006-2007
1. Eomesodermin (Eomes) and Smad functional interactions in activating the Xenopus Eomes promoter.
2. Physical interactions between Eomes, Smads and the Xenopus Eomes promoter activin response element.
3. The role of Eomes in Xenopus cardiac development: (A) comparison of different conditional GR-Eomes-enR and GR-Eomes-VP16 constructs in their effect on heart development; (B) search for cardiac Eomes protein partners.
4. The role of Eomes in cardiac development: conditional deletion of Eomes in the mouse embryonic heart.
5. The role of Eomes in mesoderm differentiation: Identify Eomes target genes. Xenopus: conditional Eomes construct [GR-Eomes] plus cycloheximide. Mouse: Eomes knockout ES cells and microarray analysis.
6. The role of Eomes in neural stem cell differentiation: Eomes knockout ES cells.

Lab personnel:
Paola Picozzi (Post Doctoral Fellow)
Tiziana De Angelis
Ning Dai

Research Assistant Professor of Pediatrics at University of Pennsylvania School of Medicine (2001 – 2009)
Ph.D., Biological Chemistry, Johns Hopkins University School of Medicine (1993)
B.S., Biology, SUNY Stony Brook (1982)
Selected Publications
Ryan K, Levy RJ. Evidence that Eomesodermin is Important in Cardiac Development. Poster presentation, Weinstein Cardiovascular Development Conference, Boston, MA. 2003.
Ryan K, Chin AJ. T-Box Genes and Cardiac Development. Birth Defects Res. (Part C). Vol 69. 2003:25-37.
Ryan, K. and Chin, A.J.. T-box genes and cardiac development. Birth Defects Res. (Part C). Vol 69. 2003:25-37.
Ryan K, Wehr DJ, Jennings JS, Levy RJ. Eomesodermin is a Crucial T-Box Gene in Vertebrate Cardiac Development. Poster presentation, Weinstein Cardiovascular Development Conference, Salt Lake City, UT. 2002.
Ryan K, Wehr DJ, Levy RJ. Eomesodermin is a Crucial T-Box Gene in Vertebrate Cardiac Development. Poster presentation Gordon Research Conference on Cardiac Regulatory Mechanisms, New London, CT. 2002.
Ryan K, Wehr DJ, Jennings JS, Levy RL. Eomesodermin is Required in Development for Cardiac Mesoderm Induction, Looping, and Outflow Tract Formation. Circulation suppl. 106: II-285(1438). Basic Science poster presentation at the American Heart Association Scientific Sessions, Chicago, IL. 2002.
Itoh T, Itoh A, Horiuchi H, Ryan K, Pleasure D. Xenopus Laevis Glyceraldehyde-3-phosphate dehydrogenase type B. GenBank Accession Number AF549496. 2002.
Taelman V, Avalosse B, Opdecamp K, Ryan K, Bellefroid EJ. Cloning and Expression of the bHLH Encoding Gene, Xath2, Expressed in the Forebrain of Xenopus Embryos. Mech. Dev.. Vol 101. 2001:199-202.
Levy RJ, Song C. Tallapragada S, DeFelice S, Hinson JT Vyavahare N, Connolly J, Ryan K, Li Q. Localized Adenovirus Gene Delivery Using Antiviral IgG Complexation. Gene Ther.. Vol 8. 2001:659-667.
Ryan K, Hazelwood SK, Levy RJ. Eomesodermin (Eomes) is Expressed in Heart Development and Disease. Presented at the Annual Poster Day Meeting, Children's Hospital of Philadelphia, Philadelphia, PA. 2001.