Over the past several years, gene editing has become a powerful tool for creating cellular models of human diseases, particularly with the emergence of technologies like CRISPR-Cas9.
But one concern with gene editing tools like CRISPR which allows scientists to cut and paste genetic sequences into a genome to correct errors or introduce changes is precision, says Krishanu Saha, a bioengineering professor at the University of WisconsinMadison. That is, editing genes sometimes introduces errors that could have unintended consequences.
Saha is using CRISPR to reprogram human pluripotent stem cells and immune cells to study diseases like Fragile X syndrome, to discover new drugs and develop cell therapies, and to ask fundamental questions about human biology. On Wednesday, April 19, he will present the strategies his lab has developed to make gene editing more precise at the 12th Annual Wisconsin Stem Cell Symposium.
My talk is focused on genome-level engineering of human cells, Saha says. I will cover ongoing work in my lab that engineers human pluripotent stem cells and T cells from cancer patients.
The strategies Saha and his research team have developed help correct pathogenic point mutations and introduce transgenes with precision, reducing and in some cases eliminating undesirable genomic effects.
Another UWMadison scientist, Professor of Chemical and Biological Engineering Eric Shusta, is using stem cells to explore the biology of the blood-brain barrier. This work will be the subject of his talk at the symposium, which is hosted by the UWMadison Stem Cell and Regenerative Medicine Center (SCRMC) and the BioPharmaceutical Technology Center Institute (BTCI).
The blood-brain barrier is an impermeable network of endothelial cells that protects the brain from toxins and other potentially harmful agents that may be circulating in the blood. A healthy blood-brain barrier is essential for well-being, but issues with this security system for the brain can lead to developmental or other types of disease.
Using stem cells, Shusta and his colleagues have been able to reconstruct the blood-brain barrier in the laboratory dish, providing scientists with a potent model for drug discovery and to explore neurological disorders that may be associated with a compromised barrier. The advent of patient-sourced induced pluripotent stem cells means it may be possible to mimic diseases or conditions and possibly devise treatments for disorders that are now untreatable.
The symposium will also gather a handful of national and international speakers, like Memorial Sloan Kettering Cancer Centers Michel Sadelain (New York) and Leiden University Medical Centers Christine Mummery (The Netherlands), focused around the theme: Engineering Cells and Tissues for Discovery and Therapy.
We sought to bring bioengineers together with biologists and clinicians this year, says Saha, who is also a co-organizer of the event with UWMadison Professor of Chemical and Biological Engineering Sean Palecek. Because bioengineers are working at many levels the genome, cell and tissue we have invited scientists across these scales.
Talks will focus on emerging strategies to control stem cell behavior in the lab and in the body and include genome and cell engineering; stem cells as models of cell and developmental biology; in vitro maturation of stem-cell derived tissues; tissue engineering and organoid development; biomanufacturing; and treatments utilizing engineered human cell products.
We see great synergy in bringing together techniques of controlling behavior across these scales to generate new research tools and therapeutics, Saha says.
Moderators of the symposium include Timothy Kamp, professor of medicine and co-director of SCRMC ; William Murphy, professor of biomedical engineering, orthopedics and rehabilitation, and co-director of SCRMC; Saha and Palecek. It takes place from 8:30 a.m. until 6 p.m. at the BioPharmaceutical Technology Center, 5445 E. Cheryl Parkway, Fitchburg, Wisconsin 53711.
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