Ipsita Banerjee, PhD

930 Benedum Hall | 3700 O’Hara Street | Pittsburgh, PA 15261 P: 412-624-2071 C: 412-624-2041

ipb1@pitt.edu Associate Professor

Department of Bioengineering (Secondary) McGowan Institute for Regenerative Medicine

Our research group is organized around design and development of engineering strategies for next-generation therapy. On one hand we design engineering tools for stem cell based regenerative therapy. In parallel we develop systems level mechanistic models of cell signaling pathways for various disease models as well as to understand self-renewal and differentiation of pluripotent stem cells.

Systems Analysis of Cell Signaling Pathways

Cells sense and respond to their surrounding environment via cell signaling pathways, which is critical for their normal function. Deregulation of these pathways results in pathogenic conditions. Our goal is to develop experimentally verified mathematical models of the cell signaling pathways critical for the normal function of the cells, and identify specific deregulations resulting in pathogenic conditions. In particular we have developed mechanistic model of the PI3K/ AKT pathway driving self-renewal of human pluripotent stem cells and TGFβ pathway driving their endoderm specific differentiation. These two pathways have strong interactions between them, which we resolve using Boolean models and Dynamic Bayesian Networks. During the process of differentiation the cell cycle behavior of stem cells also undergo a rapid dynamic transition. We use stochastic population models to track this dynamics of cell cycle transition from population level experimental data. This approach allows us to quantify the heterogeneity in the cell population, and the evolution of heterogeneity with differentiation.

Engineering of Regenerative Organs

Functional organs typically rely on the coordinated function of multiple organ specific cell populations. Supporting vasculature and mesenchyme are also known to be key contributors to proper organ function. Our goal is to engineer human pancreatic islets by reconstructing the islet’s native microenvironment. We are designing multi-component ‘organoid’ systems composed of stem cell derived pancreatic cell populations, engineered microvasculature, and supporting mesenchyme. The organoid spontaneously self-organizes on a designed hydrogel to synergize vascularization with islet maturation. This platform allows us to closely capturing the intricate cooperative relationship between islet cell populations. We also design composite natural hydrogels to facilitate three dimensional culture and differentiation of stem cells. These scaffolds, derived from alginate, chitosan, fibrin, and native decellularized pancreas ECM provide physical cues to the encapsulated cells, along with enhancing the effect of soluble chemical cues. Cell-cell interactions established by the 3-D scaffolds along with cell-extracellular matrix interactions synergize towards enhanced functionality of the differentiated phenotype.