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I received my B.A. from Smith College in 1979, and my Ph.D. from Tufts University in 1989. Since 1993 I have been a member of the staff at the Forsyth Institute, Department of Cytokine Biology, and I also hold an appointment as an instructor in the Department of Oral and Developmental Biology at the Harvard School of Dental Medicine. Major Research Interests The major focus of my laboratory is the molecular genetic analysis of craniofacial cartilage, bone and tooth development. Our primary model is that of the zebrafish, Danio rerio, which exhibits significant nucleotide and amino acid sequence identity to higher vertebrates including mouse and man. Strengths of the zebrafish include high fecundity, extra-utero fertilization, and rapid growth. Zebrafish are particularly well adapted for a variety of molecular genetic techniques including mutagenesis, cell transplantations, fate mapping, and microinjection studies. Their transparency throughout development makes them well suited for fluorescent and confocal analyses. The ability to perform saturation mutagenesis screens in zebrafish makes them useful for the identification of all of the genes acting within a particular developmental pathway, including that of craniofacial and tooth development. As TGFβ signaling is critical for craniofacial development,
early efforts in my laboratory focused on the isolation and characterization
of TGFβ family member receptors in zebrafish. These studies
were extremely fruitful, resulting in the identification of four
zebrafish TGFβ family member receptors, including a novel type
I receptor, alk8, which appears to be conserved in higher
vertebrates including mouse and man. Functional studies of constitutively
active and dominant negative Alk8 isoforms demonstrate
that alk8 is required for neural crest cell formation and
mediolateral specification, for early dorsoventral patterning of
the embryo, and in later developmental events including zebrafish
tooth development and craniofacial cartilage and osteoblast differentiation.
Characterization of alk8 expression in mouse and human
craniofacial development demonstrates evolutionary conservation
in higher vertebrates. Our studies on alk8 facilitated
the identification of a zebrafish alk8 mutant, lost-a-fin,
an invaluable tool for in vivo analysis of alk8. We are also exploiting the fact that zebrafish exhibit continuous tooth generation to elucidate molecular signaling cascades of adult replacement tooth formation, with the anticipation that these studies will reveal molecular cascades that can be used in our efforts to grow teeth in humans, in situ, in the jaw. We have recently embarked on a large-scale mutagenesis screen in zebrafish, to identify mutations in replacement tooth development. To date, relatively very few pathways regulating craniofacial development have been elucidated at the molecular genetic level. Using high-throughput screening methods we will identify zebrafish harboring point mutations in genes required for craniofacial cartilage, bone and tooth formation. The mapping and identification of each mutated gene, tasks greatly facilitated by the creation of recently developed molecular genetic tools in zebrafish, will likely result in the identification of novel genes that are conserved in humans. Functional analysis of these genes, using techniques we have mastered in our analysis of alk8, will rapidly provide information that is likely to facilitate the design and implementation of therapies to treat human craniofacial syndromes, and in particular, to facilitate replacement tooth formation in humans. Selected Publications 1. DeCaestecker, M., Payne, T.L., and Yelick, P.C. (2002) Alk8 is a signaling partner of TGFβ and TGFβRII. Biochem Biophys Res Commun. 293(5):1556-65. 2. Bang, P., Yelick, P.C., Malicki, J., and Sewell, W. (2002) High-throughput behavioral screening method for detecting auditory response defects in zebrafish. J. Neuroscience Methods, 118(2): 177-187 3. Yelick, P.C. and Schilling, T. (2002). Molecular Dissection of Craniofacial Development in Zebrafish, Critical Reviews in Oral Biology and Medicine 13(4):308-22. 4. Young, C.S., Terada, S., Vacanti, J.P., Masaki, H., Bartlett, J.D., and Yelick P.C. (2002) Tissue engineering of complex tooth structures on biodegradable polymer scaffolds. Journal of Dental Research, 81(10):695-700. 5. Young, C.S., Terada, S., Vacanti, J.P., Masaki, H., Bartlett, J.D., and Yelick P.C. (2003) The Regenerated Tooth: Tissue engineering of complex tooth structures on biodegradable polymer scaffolds. Journal of Dental Technology, April/May, pp 21. 6. Perrino, M. and Yelick, P.C. (2003) Alk8 is reiteratively expressed in developing zebrafish pharyngeal teeth. Cells, Tissues and Organs, (In press). 7. Payne, T.L., Lee, M.A., Whitman, M., and Yelick, P.C. (2003) Alk8 Specification of Neural Crest and Pharyngeal Arch Cartilages, Developmental Dynamics, (In press). 8. Yelick, P.C. and Vacanti, J.P. (2003) “Dental Stem Cells”, Handbook of Adult & Fetal Stem Cells, Edited by Irv Weissman, Doug Melton, Catherine Verfaillie, Malcolm Moore, Helen Blau, E. Donnall Thomas, Mike West and Robert Lanza. (in press). 9. Yelick, P.C. (2003) Ten Cate Handbook of Oral History, "Bioengineering Teeth: Dream or Reality?", in press. 10. Fang, P.K., Solomon, K., Freeman, M.R., and Yelick, P.C. (2003) Zebrafish (Danio Rerio) Caveolin-1a and Caveolin-1b: Indispensable Roles in Embryo Development (In preparation). |
Pamela
C. Yelick, Ph.D.Copyright
© 2003 Michael R. Freeman. All Rights Reserved.
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