gillian-dewane@uiowa.edu
Mentor: Kris DeMali, Ph.D.
Lab Room: 4-411A BSB
Lab Phone: 319-335-7662

Molecular Signaling at Adherens Junctions on Epithelial Cells in Response to Mechanical Force

All cells are subjected to mechanical force throughout their lifetimes and must respond to different environmental signals in order to grow and survive. Some of these mechanical forces that our cells experience can be seen with epithelial cells in which cell-junctions are well-employed. These cells can experience shear stress, hydrostatic pressure, osmotic force, and stretching forces. One way by which cells respond to mechanical force is via cell adhesion receptors like cadherins and integrins. Cadherins are calcium-dependent adhesion receptors which link cells to other cells at points called adherens junctions. Cadherins are able to sense forces applied to epithelial cells via their cytoplasmic domains and this transmits signals to the inside of the cell.

When force is applied on epithelial cells via cadherins, the cell recruits proteins to the adherens junction in response to the signal so that the signal can be transmitted to the actin cytoskeleton. This causes cytoskeletal rearrangements and activation of the Rho GTPase Pathway, resulting in cell stiffening. The protein Vinculin is essential to the adhesion complex and is responsible for transmitting the signal to activate RhoA. Our lab has shown that phosphorylation at site Y822 on Vinculin is necessary for the cell stiffening response. Currently, we are interested in determining the link between Vinculin and RhoA signaling, as it is unknown.

Chlenski A, Dobratic M, Salwen HR, Applebaum M, Guerrero LJ, Miller R, DeWane G, Solomaha E, Marks JD, Cohn SL. Secreted protein acidic and rich in cysteine (SPARC) induces lipotoxicity in neuroblastoma by regulating transport of albumin complexed with fatty acids. Oncotarget. 2016 Nov 22;7(47):77696-77706. doi: 10.18632/oncotarget.12773. PubMed PMID: 27776337; PubMed Central PMCID: PMC5363614.

Applebaum MA, Jha AR, Kao C, Hernandez KM, DeWane G, Salwen HR, Chlenski A, Dobratic M, Mariani CJ, Godley LA, Prabhakar N, White K, Stranger BE, Cohn SL. Integrative genomics reveals hypoxia inducible genes that are associated with a poor prognosis in neuroblastoma patients. Oncotarget. 2016 Nov 22;7(47):76816-76826. doi: 10.18632/oncotarget.12713. PubMed PMID: 27765905; PubMed Central PMCID: PMC5340231.