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Shuibing Chen is an assistant professor in the Department of Surgery and Biochemistry at Weill Cornell Medical College, New York. She received her B.S. and M.S. in Chemistry from Tsinghua University in China. Then, she pursued her PhD under the advisement of Dr. Peter G. Schultz at the Scripps Research Institute where she started being interested in chemical biology and stem cell biology. After graduation, she joined Dr. Doug Melton’s laboratory at Harvard University to study the directed differentiation of human embryonic stem cells toward pancreatic lineage. The major research interest in the Chen Laboratory at Weill Cornell is to manipulate stem cell fate using chemical and biological approaches and to generate functional tissues and organs that can be used for translational research. Their current main focus is on human pluripotent stem cells (PSCs), including human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). They combine the knowledge of stem cell biology, developmental biology, chemical biology, medicine chemistry and tissue engineering to derive functional cells, tissues and organs from human pluripotent stem cells. Their long-term goal is to apply patient specific PSC-derived tissues or organs for replacement therapy and build up “disease in a dish” platforms for drug discovery.
Abstract: Human pluripotent stem cells, including human embryonic stem cells (hESCs) and induced pluripotent stem (iPS) cells, present unlimited starting material to generate differentiated cells that can be used for disease modeling. Essential to this pursuit is an efficient way to differentiate pluripotent stem cells into specific types of mature cells. Although some progress has been made in ESC differentiation, efficient generation of cells having the complete functional capabilities of mature human cells has not been accomplished. Achieving this goal will require the identification of novel reagents that induce differentiation and a better understanding of the signaling pathways that control human embryonic development. Cell-permeable small molecules that can modulate the function of specific proteins provide a convenient and efficient approach to controlling stem/progenitor cell fate. Ideally, small molecules will be less expensive, more easily controlled, and possibly more efficient than growth factors in directing differentiation of human pluripotent stem cells. In addition, small molecules provide a new tool for dissecting the molecular mechanisms that control embryonic development. Using chemical screening approaches, they have identified the synthetic small molecules that direct hESC differentiation into definitive endoderm, pancreatic progenitors and endocrine progenitors. After the chemical treatment, ~40% cells express NGN3, a pancreatic endocrine progenitor marker. In addition, the chemical treated population shows stronger abilities to contribute to insulin-secreting cells both in vitro and in vivo. They are studying the mechanism of action of the hit small molecules. These studies not only provide novel reagents that can control hESC differentiation, but also provide new insight into the underlying mechanism of pancreatic development. Their long-term goal is to derive functional cells that can be used for both cell replacement therapy and disease modeling.
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