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Alumnus Chong W. Yung (Ph.D. '05, chemical engineering) has published new research on biohybrid artificial organs (BAOs) that could change the way patients with cancer and other diseases receive treatment. The article, "Counteracting apoptosis and necrosis with hypoxia responsive expression of Bcl-2Delta" was recently published in Metabolic Engineering, 2006;8(5):483-90.
Biohybrid artificial organs are medical devices made from synthetic materials and living cells that, once implanted into a patient's body, make and release therapeutic drugs. Since BAOs typically do not have a blood supply, their supply of oxygen and nutrients is limited. This reduces the length of time they are able to function properly. Eventually, BAO cells tend suffer from hypoxia, a lack of oxygen, which results in decreased activity and functioning, or worse, apoptosis (self-destruction) and necrosis (death).
To address this problem, Yung and his colleagues experimented with a BAO designed to produce interleukin 2 (IL2), a cancer-fighting drug. By inserting a genetic switch called 5HRE, they engineered the BAO's cells to also manufacture a protein called Bcl2-Delta, which helps them stay healthy and productive. When low oxygen conditions are sensed by the cells, 5HRE activates the production of Bcl2-Delta, giving the BAO the ability to manage and correct its level of stress. By adding red and yellow fluorescent proteins to IL2 and Bcl2-Delta, respectively, Yung's team was able to visually monitor when 5HRE switched on, and how much IL2 and Bcl2-Delta was being produced.
Results were promising: cells with the 5HRE/Bcl2-Delta combination "showed an increased level of protein production as the oxygen was decreased" when compared with those without Bcl2-Delta, or those using a different genetic switch.
We caught up with Yung, who is now a postdoctoral fellow at the Harvard Medical School in the Ingber Laboratory, Children's Hospital Boston, to ask him how his experiences at the University of Maryland prepared him for his current work. "I would say that it was one of my most gratifying experiences," he told us. "It was not only intellectually stimulating but also socially rewarding. I was lucky to be co-advised by two great scientists and friends, [Fischell Department of Bioengineering Chair] Bill Bentley and [former chemical and biomolecular engineering Professor] Tim Barbari, who enthusiastically injected their expertise into my project on creating biohybrid artificial organs...[they] were able to blend intellectual freedom with practical boundaries that allowed me to develop myself as a creative and independent researcher."
January 5, 2007
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