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Education/Training/Licensure:
B.S. State University of New York at Plattsburgh
Ph.D. Albany Medical College
Postdoctoral Fellow: Northwestern University Medical School
Research Interests:
The organization of cells within tissues and organs such as the
skin requires cell-cell interactions that are highly specific and
tightly regulated. These adhesive interactions also need to be integrated
with cellular processes that control cell growth, differentiation
and migration. The fundamental question that our laboratory seeks
to understand is how cell-cell adhesion molecules are integrated
with the cytoskeleton, and how this adhesion and signaling system
is regulated in a manner that promotes tissue organization. We are
focused on members of the cadherin family of cell-cell adhesion
molecules, and on the proteins that interact with the cytoplasmic
domains of cadherins. Cadherins are a family of cell-cell adhesion
molecules that play important roles in development, wound healing,
and in a variety of autoimmune and genetic skin diseases. We are
particularly interested in how cadherins interact with a class of
cytoplasmic proteins termed armadillo proteins. One project in the
lab is to understand the specific functions of an armadillo family
protein termed plakophilin-4 (p0071). We are studying how plakophilin-4
binds to cadherins, and how plakophilin-4 regulates cadherin-mediated
adhesion. These studies utilize morphological approaches to determine
the subcellular distribution of plakophilin-4 in fixed and living
cells, and biochemical and genetic approaches to determine how plakophilin-4
interacts with other proteins involved in cell adhesion. A second
project in the lab is designed to understand how dermal microvascular
endothelial cells regulate cell surface levels of cadherins. We
have found that under certain circumstances, endothelial cells rapidly
internalize and degrade VE-cadherin through classical endocytic
pathways involving lysosomal degradation. We are currently dissecting
the pathway that VE-cadherin takes after internalization in order
to understand the cellular machinery that regulates VE-cadherin
cell surface levels. These studies are important because the down
regulation of cadherins is associated with tumorigenesis, epithelial
to mesenchymal transitions, and with the loss of endothelial barrier
function during inflammatory conditions. Our long-term goal is to
determine how membrane trafficking systems are integrated with cadherin
based adhesive structures in endothelial cells, and how the interface
between these two cellular systems is modulated during inflammation
and angiogenesis.
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