DERMAL ENDOTHELIAL INTERCELLULAR JUNCTIONS

Project: Research project

Project Details

Description

This application for a Mentored Research Scientist Development Award
is designed to provide the candidate with the opportunity to develop
an independent area of research focusing on the molecular and
cellular biology of dermal microvascular endothelial intercellular
junctions. The research will be carried out at Northwestern
University Medical School where the faculty have recognized expertise
in the areas of intercellular junction assembly, endothelial cell
biology, and dermatology. The formation of adhesive intercellular
junctions by vascular endothelium is thought to be critical in the
regulation of fluid balance between the plasma and tissue
compartments. The loss of this barrier function of endothelial cells
is a prevalent feature in numerous pathologies that involve
inflammation and edema, and in the skin, this psoriasis and
dermatitis. In addition, endothelial intercellular junctions may be
regulated during angiogenesis and may provide control over
endothelial cell migration into a wound area. Two types of
approaches will be taken to investigate endothelial junction
assembly. First, specific components of the junctions will be
expressed in fibroblasts to reconstitute complexes that may form
between proteins during junction assembly. This approach will allow
for the identification of protein-protein interactions
that can be further investigated using purified proteins in vitro.
Secondly, mutants of the endothelial junction proteins will be
expressed in endothelial cells to specifically inhibit the function
of the endogenous protein and identify the role of each protein in
junction assembly. By analyzing mutants that inhibit endothelial
junction assembly, the impact of improper junction formation on
endothelial cell function will be determined. Emphasis will be
placed on understanding how endothelial junctions influence the
ability of endothelial cells to function as a barrier to fluid and
solutes and how endothelial junctions may regulate migration. It is
anticipated that the results of this study will provide fundamental
information regarding the altered behavior of endothelial cells in
various cutaneous disorders that involve inflammation, edema, or
angiogenesis.
StatusFinished
Effective start/end date8/15/977/31/02

Funding

  • National Institute of Arthritis and Musculoskeletal and Skin Diseases
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases: $107,178.00
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases: $116,483.00
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases

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