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Cellular reprogramming allows for the generation of a self-renewing and patient-specific cell source for drug discovery, cell therapies, and regenerative medicine through the generation of human induced pluripotent stem cells (hiPSCs). hiPSCs can grow indefinitely in culture and retain the ability to mature into any cell type of the human body. By bringing together stem cell biology, genome engineering and biomaterials expertise, the Saha lab generates new tools for use with hiPSCs to ask unique questions about human biology and disease. Work in the lab focuses on following: 1. High-throughput, RNA-guided genome editing in living human stem cells. This project develops a novel approach to convert natural signaling components in human stem cells to synthetic, bioorthogonal ones. The approach relies on producing point mutations in living cells at defined genomic locations using Cas9/CRISPR technology. 2. Stem cell modeling of neurodevelopmental disorders. We are using customized biomaterials and genome editing to generate new human cell-based models of neural development (for example, Rett and Fragile X Syndromes). A key goal of this project is to correct mutations within diseased cells and generate isogenic co-cultures of hiPSC-derived neural cells that recapitulate neural morphogenesis and pathology seen in patients. This project exploits close collaboration with biologists and clinicians at the Waisman Center (UW-Madison). 3. Biophysical and biochemical signaling crosstalk during reprogramming. We utilize a biomaterials approach to probe biophysical regulation of human somatic cells during reprogramming. This work aims to generate a quantitative understanding of reprogramming processes from the microenvironment down to the genomic sequence in order to inform the design of new reprogramming strategies to rationally produce diverse cells for regenerative medicine and disease modeling.