Michael Smith Laboratories Seminar Series
Hosted by Dr. Peter Zandstra
Cells must carefully integrate environmental cues, including chemical and physical stimuli, so they can function properly. These cues are sensed by cellular receptors, which in turn activate a variety of intracellular signal transduction pathways and gene transcription programs. We dissect cellular signaling networks, focusing oon mechano-transduction pathways, and characterize how quantitative changes in the flow of signals can control a wide variety of cellular processes. In particular, we study how cell-cell adhesive interactions affect disease pathogenesis and how adhesive and mechanical signals combine with chemical signals to regulate stem cell fate choices.
How does cell adhesion affect disease pathogenesis? We use genetic screens to identify adhesion receptors and regulation of these receptors in the opportunistic human pathogen Candida albicans. We then characterize the roles of diverse adhesion receptors in C. albicans binding to a variety of materials used in medical devices, biofilm formation on these materials, binding to mammalian epithelial cells, and virulence in mammals. We also study how the morphogenic switch between yeast and filamentous growth forms affects adhesion, force generation, biofilm formation and virulence. Our efforts will aid development and evaluation of antifungal interventions as well as design of biofilm-resistant materials.
How do adhesive and mechanical cues affect human embryonic stem cell (hESCs) differentiation? Embryonic stem cells have the unique combination of limitless self-renewal and the ability to form any cell type found in the adult. These properties offer tremendous promise in tissue engineering and stem cell-based therapies. To harness this promise, we must understand how to effectively culture hESCs and regulate their differentiation. Stem cells make differentiation decisions based on signals from their microenvironment, including chemical and physical stimuli. We study how adhesive forces and mechanical strain affect self-renewal and differentiation of hESCs then apply what we learn to the design of methods to scale up hESC culture and to development of strategies to efficiently guide hESC differentiation to desired cell types.