In order to generate physiologically relevant in vitro tissue models, we use three dimensional cell cultures of stem cells and/or their differentiated progeny to develop platforms for pharmaceutical testing and models to recapitulate tissue development, tissue homeostasis, and disease progression.
Pharmaceutical Applications - Three dimensional models of human tissue can provide a platform for pharmacological screening that more closely predicts drug toxicity and other unwanted side effects than is currently possible with traditional 2D cell culture or with animal models. By understanding the interactions between cells and their extracellular matrix, the cross-talk between different types of cells, or the influence of morphogenic factors, we can develop methods to control these factors and build models that closely recapitulate native tissues. We are currently working toward generating functional 3D models of a variety of tissues including bone, cartilage, heart, and liver.
Disease States - In addition to generating models of healthy functioning tissue, the recent emergence of induced pluripotent cells (iPS) makes the study of patient-specific disease states possible. In our lab, we are employing methods to reprogram somatic cells combined with directed differentiation of pluripotent cells into tissue-specific states. With these new technologies, we are able to study 3D tissue models of patient specific diseases to inform the development of novel therapeutic strategies.
Developmental Models - Proper mammalian development is dependent on highly controlled spatially and temporally regulated expression of morphogenic factors. Current work in the lab focuses on understanding mechanisms that mediate the differentiation of cells throughout development and engineering technologies to control these processes in both murine and human stem cells. In parallel, we are also developing methods to scale-up or 3D cultures by assembling micro-tissues into larger structures to model larger-scale tissue development.