Reciprocal interactions of cells with their 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, but 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, Varghese will discuss efforts to delineate the role of the extracellular matrix on cellular responses relevant to tissue repair, stem cell differentiation, and disease progression.