Inquiries & INNOVATIONS

Inhibiting inflammatory enzymes

Enzymes called lipoxygenases help control the body's inflammatory responses. "We're realizing their role in human disease is quite significant," said professor of biochemistry Ted Holman, part of a group awarded two related patents for inhibitors of the lipoxygenases 12-LOX and 15-LOX-1.

Inhibiting 12-LOX could prevent a dangerous condition that afflicts some surgery patients, potentially saving lives in rare cases where heparin, a drug commonly used to prevent blood clots during surgery, instead induces platelets to aggregate excessively, triggering stroke and bleeding. And inhibiting 15-LOX-1 could help stroke patients. After an ischemic stroke, blood returns to the brain as the patient recovers. But the oxygen in the returning blood can also be harmful, and blocking 15-LOX-1 may limit the damage this can cause.

Maloney D, Luci D, Jadhav A, Holman T, Nadler J, Holinstat M, Taylor-Fishwick D, Simeonov A, Yasgar A, McKenzie S. 4-((2-hydroxy-3-methoxybenyzl)amino)benzenesulfonamide derivatives as potent and selective inhibitors of 12-lipoxygenase. U.S. Patent 10,266,488, filed October 10, 2014, issued April 23, 2019; and Van Leyen K, Holman T, Maloney D, Jadhav A, Simeonov A, Rai G. Inhibitors of human 12/15-lipoxygenase. U.S. Patent 10,287,279, filed February 19, 2016, issued May 14, 2019.

Cancer treatment maps

A cancer cell is a cell that has run amok. Exactly how this happens depends on an immense set of possible cancer-causing errors that occur with great variability among cancer types and individual patients. But identifying the specific errors could help doctors choose the best treatments—to “personalize” therapy for each patient.

To accomplish this, the patented algorithm developed by professor of biomolecular engineering Josh Stuart and collaborators compares the genomic blueprints of tumor and healthy cells. The resulting dynamic pathway map pinpoints the errors that led to the cancer—and thus possible targets for therapy. "The invention takes very complex data and focuses attention on likely treatment alternatives for patients," Stuart said.

Vaske C, Benz S, Stuart J, Haussler D. Method of generating a dynamic pathway map. U.S. Patent 10,192,641, filed October 26, 2011, issued January 29, 2019.

More efficient networks

In internet networks, databases called routing tables tell each node where to route data. When the network is large and dynamic, efficiently updating the routing tables becomes critical. "The goal is to reduce the amount of time and to reduce the amount of messages that have to be exchanged," said J. J. Garcia-Luna-Aceves, professor of computer science and engineering.

His patented method organizes nodes into hierarchical groups, so that not every node has to store and send every message about how to update the tables. The approach would be especially useful for special-purpose wireless networks that are constantly changing, such as ones used for disaster relief or on the battlefield.

Garcia-Luna-Aceves J, Li Q. Method for distance-vector routing using adaptive publish-subscribe mechanisms. U.S. Patent 10,091,094, filed October 16, 2014, issued October 2, 2018.

Finding gut leaks

The sugar substitute sucralose can't be digested, so it usually exits the body via the bowel. But finding it in urine or blood could signal a leak in the gut, due to inflammation from Crohn's disease or another gastrointestinal disorder. Doctors typically perform colonoscopy to evaluate such leaks. But measuring sucralose could be simpler, quicker, and cheaper—perhaps as an initial screening.

To readily detect and measure sucralose in urine or blood, professor of organic chemistry Baktham Singaram and collaborators invented a chemical process that causes a sample to glow with a brightness proportional to the sucralose concentration. In addition, the time between sucralose ingestion and its appearance in urine or blood reveals the leak’s location. "Using our procedure, we can say globally where the leak is," Singaram said.

Singaram B, Resendez A, Webb D. Fluorescence method for sensing chlorinated disaccharides. U.S. Patent 10,274,483, filed June 5, 2015, issued April 30, 2019.

RNA-targeted therapy

A cancer cell or virus can be inhibited by severing its RNA, the coiled molecule that transmits its genetic material. But to prevent toxic side effects and the development of resistance, the RNA has to be cut in specific places along its sequence. Such precise slicing can be done with ribozymes, a type of RNA that acts like an enzyme.

To get the right ribozymes, William Scott, professor of chemistry, and Sara O'Rourke, project scientist, invented a way to engineer simplified “hammerhead” ribozymes. "It really increases our flexibility to design a potent inhibitor for pretty much any RNA molecule you could want to target," Scott said. The researchers are applying their technique to develop drugs for chronic myelogenous leukemia and RNA-based viruses, like the Covid-19 coronavirus.

O'Rourke S, Scott W. Catalytic strands of minimal hammerhead ribozymes and methods of using the same. U.S. Patent 10,301,626, filed March 1, 2016, issued May 28, 2019.