Structural Studies of Dynamic Cellular Processes
University of Washington, Seattle; Postdoctoral, 1995-1999. University of California, Los Angeles; Ph.D., 1995. University of California, Davis; B.S., 1990. Burroughs Wellcome Career Award in the Biomedical Sciences 1999-2005, Phillip and Ruth Hettleman Prize for Artistic and Scholarly Achievement, 2004.
Discovery Blocks Cancer Drug's Toxic Side Effect
Findings published in Science from the Redinbo Group, in collaboration with UNC School of Medicine, the Albert Einstein College of Medicine, and North Carolina Central University, may lead to the elimination of a debilitating side effect of CPT-11, a widely used but harshly potent treatment for colon cancer. The team of researchers, led by chemistry professor Matthew Redinbo from the University of North Carolina at Chapel Hill, has discovered that it is possible to target and block the enzyme, beta glucuronidase, which is thought to play a major role in causing the drug's side effects. "In a manner of speaking, we cured the bacteria's sweet tooth without damaging the microbes or intestines and, in the process, the drug's toxic side effect was alleviated," said Redinbo.
Study co-author, Sridhar Mani, professor of medicine and genetics at Einstein, said the severe diarrhea caused by CPT-11 can sharply limit the dosage that cancer patients can receive. "Our tests showed conclusively that the inhibitor identified by our UNC colleagues prevented diarrhea in mice that were also receiving CPT-11. We are hopeful that clinical trials will show that administering this inhibitor when patients start taking CPT-11 allows for improvement in the drug's anti-tumor effect in patients with cancer."
One Atom Controls Bacterial Walking
Several bacterial pathogens require the "twitching" motility produced by filamentous type IV pili (T4P) to establish and maintain human infections. Two cytoplasmic ATPases function as an oscillatory motor that powers twitching motility via cycles of pilus extension and retraction. The regulation of this motor, however, has remained a mystery. In a collaborative work published in PNAS, members of the Redinbo Group have discovered that a single atom - a calcium, in fact - can control how bacteria walk.
By resolving the structure of a protein involved in the movement of the opportunitistic human pathogen Pseudomonas aeruginosa,the scientists identified a spot on the bacteria, that when blocked, can stop it in its tracks. The finding identifies a key step in the process by which bacteria infect their hosts, and could one day lead to new drug targets to prevent infection.