You might have thought Conrad Prebys had been given 50 yard-line seats to the Super Bowl—that’s how thrilled he was to visit Sanford-Burnham. Two years ago, Prebys made a $10 million gift to support chemical genomics at the Institute. He stopped by on February 10 to learn how the research at the Conrad Prebys Center for Chemical Genomics is progressing and to tour one of our labs.
First the tour. Dr. Hudson Freeze studies congenital disorders of glycosolation (CDG), a family of rare diseases in which defective enzymes fail to add necessary sugar chains to proteins, creating multiple medical issues. CDG is fatal in 20 percent of affected children. While visiting the Freeze lab, Prebys met several researchers and spoke via Skype with a CDG patient, a young woman in the Netherlands who has spent a significant portion of her life in hospitals. Researchers in the Freeze lab are looking for creative ways to fix the enzyme deficiencies that cause these conditions.
At the Prebys Center, researchers described the facility’s overall capabilities and focused in on two specific conditions: liver cancer and muscular dystrophy. The Center uses a library of 700,000 small molecule compounds to find the handful that can modulate single proteins. They are working to shut down a specific protein implicated in liver cancer and have found a number of compounds that show promise. The next steps require optimizing the compound—changing its chemical composition to make it more effective and less toxic. An optimized compound, also known as a lead compound, could go on to become a new anti-cancer drug.
The Center’s approach to muscular dystrophy (MD) is a bit different. Researchers have taken skin cells from an actual patient and used them to create cell lines, both fibroblasts and induced pluripotent stem (iPS) cells, to generate a “disease in a dish” . Muscle cells in patients do not bind effectively to laminin, leading to progressively increasing muscle weakness. By using high-throughput microscopy to determine the ability of patient-derived cells to bind to laminin, researchers search through comprehensive collections of approved drugs to identify those that can reverse the defect. The hope is that drugs from this screen can be repositioned to help patients overcome the disease.