The general theme of my research career has been to determine the molecular basis by which the Wnt signaling pathway activates expression of target genes and subsequently affects the generation of a particular cell type, in a context-dependent and temporal manner. The Wnt signaling pathway and its components are used reiteratively throughout embryonic development and in mature tissues during the transformation of normal cells to cancerous ones, demonstrating the importance of this pathway. Wnt signaling plays a significant role in the development of the neural crest, a population of migratory cells that helps pattern the embryo. Because of its contribution to embryonic structures, defects in neural crest development give rise to multiple syndromes, diseases, and cancers, including Axenfeld-Rieger, Di George and Treacher-Collins syndromes, and neurofibromatosis. To further understand how Wnt signaling regulates neural crest development, I have performed a screen to identify novel targets of Wnt signaling involved in this process. Furthermore, investigation into the role of known Wnt target genes, such as Snail2 (Slug) allows me to elucidate how Snail2 regulates expression of its molecular targets in the context of neural crest development. Embryological and biochemical methods will be employed to determine the functional significance of these targets and their mode of regulation by Wnt. Overall, these approaches will provide me with a group of candidate molecules that will likely function in the generation of structures derived from the neural crest, such as the craniofacial skeleton and peripheral nervous system, as well as provide insight into the development of neural crest-derived cancers. In summary, my long-term research and career objectives include conducting mentored research (in the final years of my postdoc) and independent research (as a principal investigator) to elucidate the molecular mechanism underlying Wnt signaling during the development of the neural crest, and applying this knowledge to human development as a whole. This research is relevant to public health because of the biological significance of the neural crest to the proper formation of human bodies, such as the bones of the face, nerves and skin pigment cells. How neural crest cells properly become such diverse structures can help us comprehend what happens when neural crest development is impaired, and human syndromes and cancers arise.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Transition Award (R00)
Project #
4R00HD055034-02
Application #
7484876
Study Section
Special Emphasis Panel (NSS)
Program Officer
Henken, Deborah B
Project Start
2006-12-01
Project End
2010-11-30
Budget Start
2007-12-01
Budget End
2008-11-30
Support Year
2
Fiscal Year
2008
Total Cost
$244,021
Indirect Cost
Name
University of Maryland College Park
Department
Veterinary Sciences
Type
Schools of Earth Sciences/Natur
DUNS #
790934285
City
College Park
State
MD
Country
United States
Zip Code
20742
Padmanabhan, Rangarajan; Taneyhill, Lisa A (2015) Cadherin-6B undergoes macropinocytosis and clathrin-mediated endocytosis during cranial neural crest cell EMT. J Cell Sci 128:1773-86
Fairchild, Corinne L; Conway, Joseph P; Schiffmacher, Andrew T et al. (2014) FoxD3 regulates cranial neural crest EMT via downregulation of tetraspanin18 independent of its functions during neural crest formation. Mech Dev 132:1-12
Wu, Chyong-Yi; Taneyhill, Lisa A (2012) Annexin a6 modulates chick cranial neural crest cell emigration. PLoS One 7:e44903
Wu, Chyong-Yi; Jhingory, Sharon; Taneyhill, Lisa A (2011) The tight junction scaffolding protein cingulin regulates neural crest cell migration. Dev Dyn 240:2309-23
Jhingory, S; Wu, C-Y; Taneyhill, L A (2010) Novel insight into the function and regulation of alphaN-catenin by Snail2 during chick neural crest cell migration. Dev Biol 344:896-910
Taneyhill, Lisa A (2008) To adhere or not to adhere: the role of Cadherins in neural crest development. Cell Adh Migr 2:223-30