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Research Spending & Results

Award Detail

Doing Business As Name:University of Maryland College Park
  • Lisa A Taneyhill
  • (301) 405-0597
  • Peter Nemes
Award Date:06/03/2020
Estimated Total Award Amount: $ 1,200,000
Funds Obligated to Date: $ 1,200,000
  • FY 2020=$1,200,000
Start Date:06/15/2020
End Date:05/31/2024
Transaction Type:Grant
Awarding Agency Code:4900
Funding Agency Code:4900
CFDA Number:47.074
Primary Program Source:040100 NSF RESEARCH & RELATED ACTIVIT
Award Title or Description:Coordinated regulation of EMTs by cadherin proteolytic products
Federal Award ID Number:1947169
DUNS ID:790934285
Parent DUNS ID:003256088
Program:Animal Developmental Mechanism
Program Officer:
  • Anthea Letsou
  • (703) 292-8417

Awardee Location

Street:3112 LEE BLDG 7809 Regents Drive
County:College Park
Awardee Cong. District:05

Primary Place of Performance

Organization Name:University of Maryland
Street:1473 Animal Sciences Center, 812
City:College Park
County:College Park
Cong. District:05

Abstract at Time of Award

Non-Technical Paragraph: Organisms frequently direct stationary cells to become migratory in order to build various structures throughout their body plan. One such migratory cell type, the neural crest, gives rise to portions of the heart, components of the gut and sensory nervous systems, skin pigment cells, and the head skeleton. The central question of this research is to investigate the pathways controlling how neural crest cells become migratory. To address this question, an innovative, multidisciplinary approach will be taken that spans the single cell to whole embryo. Results from these experiments will shed light on processes regulating neural crest cell migration, providing immediate relevance with respect to the fundamental mechanisms controlling the directed movement of cells during development and maintenance of adult tissues. The broader impacts of this project will occur by providing 1) experiential research opportunities for both underrepresented groups at a local high school and college as well as University of Maryland undergraduates as part of their teaching certification and 2) professional development opportunities through the integration of research and teaching at the undergraduate, graduate, and postdoctoral levels. As such, this project will help better prepare the next generation of scientists for careers in both academic and non-academic settings. Technical Paragraph: The objective of this project is to uncover mechanisms underlying epithelial-to-mesenchymal transitions (EMTs) by studying the role of cadherin proteolytic peptides, extracellular N-terminal fragments (NTFs) and intracellular C-terminal fragment 2 (CTF2), using chick cranial neural crest cells (NCCs). Cranial NCC EMT requires multiple cellular and molecular changes, including Cadherin-6B proteolysis to decrease adhesion among NCCs as well as the segregation of NCCs from the neural tube basement membrane. The Taneyhill lab’s publications have demonstrated that Cadherin-6B NTFs and CTF2 promote NCC EMT through distinct mechanisms. NTFs activate matrix metalloproteinase 2 and enhance degradation of the extracellular matrix within the basement membrane through which premigratory NCCs must emerge, while CTF2 binds to β-catenin and interacts with chromatin to transcriptionally activate NCC EMT effector genes. Through a novel mass spectrometry assay, the lab has now identified (and confirmed) NTF interacting proteins. Moreover, the lab has recently discovered and validated new targets of CTF2 during NCC EMT through RNA-sequencing. Building on these results, the aims of the research are 1) to define the function of Cadherin-6B NTFs in promoting EMT and 2) to determine the role, and the mechanism(s) of regulation, of CTF2 target genes during NCC EMT. These aims will be achieved using biochemistry; molecular perturbation and genomics assays; and immunohistochemistry coupled with high-resolution confocal laser scanning microscopy with Airyscan detection. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

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