Angela Wandinger-Ness
Professor & Assistant Dean for Graduate Studies
The Wandinger-Ness laboratory studies intracellular membrane transport and epithelial cell polarity.
Efforts in the area of membrane trafficking are directed toward elucidating the functions of specific rab GTPases involved in endocytic membrane transport. The rab GTPases are constituents of a complex machinery controlling intracellular membrane transport. Rab7 is a key regulator of transport from early to late endosomes and mutations in rab7 are associated with Charcot-Marie Tooth Disease. The rab7 GTPase is important for controlling the flux of both newly synthesized lysosomal proteins and molecules internalized from the cell surface to late endosomes and lysosomes. Work is in progress to define the interactions between rab7 and other regulatory factors such as phosphatidyl inositol 3-kinases, FYVE finger domain proteins and components of the proteasome.
Work in the area of epithelial cell biology is focused on the defects in polarized exocytosis and cell polarity associated with the highly prevalent genetic disorder, autosomal dominant polycystic kidney disease (ADPKD). Mutations at the PKD-1 locus, encoding the polycystin-1 protein, are causal in 80% of all cases. Our laboratory has correlated mutant polycystin-1 protein expression with a significant alteration in cell-cell adhesion. Changes in cell-cell adhesion are apparent both in structural and functional assays and are in part precipitated by the disruption of a normal signaling domain that is comprised of polycystin-1, E-cadherin and flotillin-2 in the disease cells. The essential nature of the E cadherin/polycystin-1 complex in the establishment and maintenance of stable adherens junctions offers insight into the molecular mechanisms underlying the dramatic loss in epithelial cell polarity and differentiation associated with ADPKD. Complementary genomic and cell biologic approaches are being applied in parallel to further delineate the mechanisms leading to disease pathogenesis.
The laboratory utilizes state-of-the-art cell and molecular biology approaches, sophisticated microscopic imaging technology, including live cell imaging and laser scanning confocal microscopy, protein biochemistry and genomics to study these problems.
