Shyni Varghese, Associate Professor of Bioengineering, UC San Diego

“Unraveling the Impact of Extracellular Matrix in Tissue Regeneration and Disease”

Reciprocal interactions of cells with their surrounding microenvironment are fundamental to multiple cellular processes necessary for tissue development, homeostasis, and regeneration. It is becoming increasingly apparent that while the extracellular environment normally maintains tissue homeostasis, when negatively perturbed, it may also contribute to disease progression and age dependent pathologies. However, it is still unknown how the extracellular matrix contributes to tissue regeneration and how changes in the extracellular matrix induces differential cellular responses in diseases. In this talk, I will discuss our efforts to delineate the role of the extracellular matrix on various cellular responses relevant to tissue regeneration and disease progression. First, we have developed a bone-like synthetic matrix by utilizing biomimetic approaches and studied the role of extracellular matrix cues on stem cell commitment both in vitro and in vivo. When used to treat bone defects, these biomimetic matrices recruited endogenous cells to repair the defects, in addition to directing cell fate. These biomimetic matrices have also allowed us to further unravel the molecular mechanism by which the biomimetic matrices promote bone tissue formation and to delineate the role of native bone-matrix on bone physiology. Second, we developed a single cell invasion assay to gain a quantitative understanding of cancer metastasis and the role of extracellular matrix properties during this process. Our findings how that the cells transition from a proteolytic independent mode of invasion into a dependent mode upon an increase in the mechanical resistance from the extracellular environment. The cells apply a finite amount of force to activate the “switch” between proteolytic independent blebmediated invasion to proteolytic dependent invadopodiamediated invasion. We have also uncovered the mechanism by which MT1-MMP, a key component of invadopodia, is transported from the cytoplasm of the cells to its periphery and the role of traction force on this process.

When: Thursday 4/25 4:10 pm

Where: 1005 GBSF