Current research projects
Our laboratory is primarily concerned with determining how cellular adhesion to extracellular matrix (ECM) molecules in 3D space elicits specific cellular responses, including growth, differentiation, and migration. Our work is closely integrated with the graph theoretical work done by Dr. Bülent Yener’s group in the Department of Computer Sciences. We work with human mesenchymal stem cells and cancer cells encapsulated in purified ECM protein gels as our model system. Our general hypothesis is that adhesion to ECM molecules activates a subset of intracellular signaling pathways associated with integrin receptors, and that this signaling controls cell behaviors by modulating the organization of the cytoskeleton and ECM. Our research has both basic and applied elements, and is organized into two major projects:
(1) Differentiation of human mesenchymal stem cells (hMSC) plated in/on defined ECM proteins: We are defining the effect of ECM contact on human mesenchymal stem cell differentiation. Our hypothesis is that contact with distinct ECM proteins stimulates specific signaling pathways that ultimately control the differentiation of these cells into bone-, cartilage-, or fat-producing cells. We are working with Dr. Yener’s group to model and investigate cellular response to a variety of extracellular stimuli. The project is subdivided into two subprojects, which are: (a) Modeling of tissue formation using graph theoretical methods, and (b) Identifying the role of key intracellular signaling pathways in controlling hMSC differentiation. Collectively, these studies should help us better understand the mechanisms governing hMSC differentiation and how to capitalize on this knowledge in tissue engineering applications.
(2) Tissue and tumor structure evolution in defined ECM environments. Our overall hypothesis is that tumor progression from benign tumor to metastatic cancer is accompanied by signature changes in the 3D organization of the tumor cells, and that these changes reflect alterations of the basic principles governing tissue structure and function. We are working with Dr. Yener’s group to model these tumors and identify graph features that discriminate between different types and stages of tumor development. We are also defining the mechanism of action of anti-migration drugs with this system.
From time to time, positions open up for new students in our laboratory. Interested students please check the prospective student information page.