Vishwa Vasani

BioE PhD Proposal Presentation

March 6th, 2024

2:00 PM

Krone Engineered Biosystems Building (EBB) Room 4029

 https://gatech.zoom.us/j/97211649243?pwd=bjdyN1IwYVBXODQ5dG9zTWV1bUg4Zz09

Advisor:         Dr. Shuichi Takayama, Wallace H. Coulter Department of Biomedical Engineering

Committee:    Dr. Andrés García, George Woodruff School of Mechanical Engineering

Dr. Yesim Gokmen-Polar, Emory University, Department of Pathology and Laboratory Medicine

Dr. Todd Sulchek ,George Woodruff School of Mechanical Engineering

Dr. Cheng Zhu, Wallace H. Coulter Department of Biomedical Engineering

Mechanical Regulation of Basement Membrane Breaching in Cancer Invasion: Insights from Mammary Duct Organoids

This proposal explores the influence of native Basement Membrane (nBM) mechanics on BM-breaching cancer invasion associated with Ductal Carcinoma in Situ (DCIS) to Invasive Ducal Carcinoma (IDC) progression in breast cancer. By utilizing mammary duct organoids scaffolded with minimal Matrigel, the proposed study aims to develop a mechanophenotypic characterization method sensitive to cell-produced and cell-assembled nBM stiffness and examine how variations in organoid culture conditions affect their mechanical properties and susceptibility to cancer invasion. The research will focus on Organoid Surface Tension (OST) and viscoelasticity as key mechanical metrics, proposing that OST would reflect the mechanical properties of the organoid shell comprising the cell layer and nBM. The proposed study will characterize OST and its correlation with cancer invasion, modify organoid BM composition to test OST sensitivity, and culture organoids with patient-derived decellularized ECM to assess their cancer invasion susceptibility and mechanical properties. Additionally, it will explore nBM softening through Netrin-4 and its impact on cancer invasion, investigating the role of the Focal Adhesion Kinase pathway in mediating cancer cell response to nBM stiffness. This comprehensive approach seeks to uncover novel insights into the mechanical drivers of cancer progression, offering potential for improved predictive markers and therapeutic targets.