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Kevin Morris

Manipulating the Function and Power of Genes to Treat HIV and Cancer

Scripps Research Associate Professor Kevin Morris’s path as a scientist is a particularly unusual one. “For starters, I was a lousy student in high school, usually at the bottom of whatever class I was in, and I never gave science a thought,” said Kevin. But something happened in 1986 that changed Kevin’s life dramatically. That “something” was the headline-grabbing spread of HIV.

“My imagination was captivated by the idea that a virus – something you can’t see – can kill people. How did this killer operate? And what could we do to stop it?”

Kevin caught fire in his high school molecular biology class, going from worst to first. This sudden ascendancy was met with skepticism by his teacher. “On the mid-term, after I’d made the highest score, he said, ‘I think you cheated on this, but I just can’t figure out how,” Kevin recalls, laughing.

As an undergraduate student focusing on wildlife and ecology at Humboldt State, he continued to be intrigued by the HIV virus, an intense interest that led him to the University of California, Davis, and a Ph.D. in 2001. Kevin did postdoctoral research in this field at the University of California, San Diego (UCSD), and then worked as a research scientist at the City of Hope before coming to Scripps Research in 2005 because of the high-powered science performed here.

Kevin has been named one of 30 “Tomorrow’s PIs (Principal Investigators)” by Genome Technology Magazine. The investigators chosen to be Tomorrow’s PIs were selected for their innovative work and research in a discipline that’s part of the systems biology field.

Kevin’s research here is on RNA interference (RNAi). Also known as RNA silencing, RNAi is the introduction of double-stranded RNA into a cell to inhibit the expression of a gene associated with a disease. In our lab, we started asking whether we could use small interfering RNA to target gene promoters and turn the gene off or on at that level – transcriptional gene silencing,” said Kevin. “And we accomplished this.”

Not only did they accomplish it, but Kevin and his colleagues were able to turn the gene off after a two day treatment for up to 30 days. “As the silencing is epigenetic, it is very possible that it would be long-term and stable,” said Kevin.

“Over the past few years it has become increasingly apparent that many RNA-mediated modes of gene regulation are operative in biological systems,” Kevin explained. “Now scientists are beginning to understand just how pervasive this network is and to what extent it may be possible to apply this phenomenon for therapeutic benefit.”

Kevin describes the lab work as “solid but unspectacular science in action. It’s not dramatic – the dramatic aspect of the work is the questions we’re asking and the unique answers we’ve gotten.”

Kevin has shown the mechanism where small interfering RNAs when put into the cell, cause a specific upregulation in expression of the targeted gene. He and his colleagues discovered that the RNAs targeted a RNA-based suppressor, and that this action resulted in a loss of suppressor and turned up the specific gene.

“This was a really big discovery because the RNA-based suppressor was a non-coding RNA, which is thought to make up around 98 percent of the genome,” said Kevin elatedly. “We have been able to suggest some answers, with a few concrete examples, as to what the 98 percent of the genomes are doing.”

Kevin, whose lab counts only three people, including himself, was the first scientist internationally to publish evidence of this RNA activation phenomenon in human cells.

“I love the discovery aspect of my work,” said Kevin. “That ‘a-ha’ moment when everything comes together and fits is very rewarding.”

The potential therapeutic benefits are enormous, according to Kevin, and he is now working to commercialize his approaches to treat and silence HIV.

“If you can find a gene that’s specifically linked to a particular disease through this process you can theoretically turn the gene off.” So far in his lab, genes of interest have been “turned down” by as much as 80 percent. “The main point is we’ve shown how to manipulate a gene’s function and power.”

Kevin’s specific interest is in utilizing RNA interference to treat HIV, and this research is also leading him to a better understanding of the way that pancreatic cancer grows and develops, and the challenge of controlling genes associated with tumors.

“I really wanted to get involved with pancreatic cancer because it is so deadly -- it has only a 5 percent survival rate over five years,” said Kevin. “I believe targeting genes and being able to turn them on and off can stop the cancer from metastasizing.”

“I am very excited about what we do,” said Kevin. “We can specifically target any gene we want. I believe we can pick just about any disease to attack.”

“I’m not very smart – I can’t remember things,” concluded Kevin. “But I think I’m pretty creative and not confined by subjectivity – I try experiments that others won’t in order to push the avenues of science further.”

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“I really wanted to get involved with pancreatic cancer because it is so deadly -- it has only a 5 percent survival rate over five years,” says Associate Professor Kevin Morris.