BME PhD Prospectus Defense - Diego Vargas Arango

1:30 pm on Wednesday, August 14, 2013
44 Cummington, Room 705
Title: "Understanding the Role of N-glycosylation in E-cadherin Stabilization and its Consequences on Cell Invasion in Oral Squamous Cell Carcinoma"

Muhammad Zaman (Chair/Advisor), BME, BU
Maria Kukuruzinska (Advisor), MCB, BU
James Galagan, BME, BU
Bela Suki, BME, BU

Cancer cells undergo multiple changes before becoming a threat to the organism, including altered cellular adhesions. Oral Squamous Cell Carcinoma (OSCC) accounts for 85% of all head and neck cancers; it ranks as one of the most morbid cancers. In OSCC, the canonical Wnt pathway is a key regulator of epithelial integrity. This pathway affects intercellular adhesion through regulation of N-glycosylation (i.e. transfer of oligosaccharides on to asparagine residues on proteins). N-glycosylation affects dynamics of the canonical Wnt pathway as well as stability of adherens junctions. This study seeks to quantify the role N-glycosylation in epithelial cell invasion. N-glycosylation has been studied through methods that look at the pathway in a single instant or in isolated cells. Our approach quantifies the role of molecular interactions in invasion in a way in which cell contacts are not disrupted by an external experimental force. A detailed understanding in time and space of regulatory mechanisms orchestrating metastasis will be achieved by observing cells leaving a spheroid grown in vitro in a 3D environment and quantifying the changes at the molecular level through a multi-scale computational model. The model accounts for cell migration by using a hybrid approach that includes agent-based and continuum modeling and combines this with numerical simulations of pathway dynamics. The proposed research will provide a novel mechanism to look at the effect of protein concentration on cell collective behavior. It is also novel in the detail at which it models cell-cell interactions in cell collectives. This research will bridge the gap in our understanding of single molecule regulation by N-glycosylation and collective migration at the cellular level. Potential findings can be used to design efficient therapeutics hindering invasion in OSCC.