Kenneth Ryan, Ph.D.
Research Assistant Professor, Pediatrics (Division of Cardiology)

Developmental Biology Program

Address

710A Abramson Research Center (ARC)
3615 Civic Center Boulevard
Philadelphia, PA 19104

Office tel.: 215-590-0606
Lab tel.: 215-590-6101
Fax: 215-590-5454
E-mail: ryank@email.chop.edu

Link(s)

Dr. Ryan at the Stokes Institute

Education

SUNY Stony Brook: BS (Biology), 1982.

The Johns Hopkins University School of Medicine: PhD (Biological Chemistry), 1992.

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.

Search PubMed for articles

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.

Recent Publications

Russ, A. P., Wattler, S., Colledge, W. H., Aparicio, S. A. J. R., Carlton, M. B. L., Pearce, J. J., Barton, S. C., Surani, M. A., Ryan, K., Nehls, M. C., Wilson, V., and Evans M. J. (2000). Eomesodermin is required for mouse trophoblast development and mesoderm formation. Nature 404:95-99.

Ryan, K., Garrett, N., Bourillot, P.-Y., Stennard, F., and Gurdon, J.B. (2000). The Xenopus Eomesodermin promoter and its concentration-dependent response to activin. Mech. Dev. 94:133-146.

Ryan, K. and Chin, A.J. (2003). T-box genes and cardiac development. Birth Defects Res. (Part C) 69:25-37.

Ryan, K., Russ, A.P., Levy, R.J., Wehr, D.J., You, J., and
Easterday, M.C. (2004). Modulation of Eomes activity alters the size of the developing heart: Implications for in utero cardiac gene therapy. Human Gene Ther. 15:842-855.

McConnell , J., Petrie, L., Stennard, F., Ryan, K. and Nichols, J.
(2005). Eomesodermin is expressed in mouse oocytes and pre-implantation embryos. Mol. Reprod. Dev. 71:399-404.

Lab

Rotation Projects

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