Tufts University professor receives NIH Director's New Innovator Award

Research could accelerate discovery of new drugs to treat difficult diseases including cancer

Joshua Kritzer, assistant professor in the School of Arts and Sciences Department of Chemistry at Tufts University, has been awarded one of 33 NIH Director's New Innovator Awards, one of the most prestigious grants awarded by the National Institutes of Health.

The NIH Director's New Innovator Award program is designed specifically to support unusually creative new investigators with highly innovative research ideas at an early stage of their career. Awards recognize the potential of projects to have a significant impact on important biomedical or behavioral research problems.

The $1.5 million grant will fund Kritzer's research into a rapid drug-screening process that may help scientists identify new drugs to treat diseases. Scientists today face a fundamental problem in the drug discovery process. Up to 90 percent of the human proteins, including many that cause cancer and other diseases, are difficult to target through traditional methods of screening.

Adapting his previous work at the Whitehead Institute for Biomedical Research, Kritzer is able to use baker's yeast to produce large collections of molecules called cyclic peptides. To do this, Kritzer inserted short snippets of DNA into the yeast cells that direct them to make the cyclic peptides. The cells then synthesize tens of millions of different cyclic peptides that can be directly tested for anti-cancer or other activities.

Cyclic peptides are important because they can bind with disease-causing proteins that scientists previously have been unable to target because they do not possess "active sites" or pockets that can easily bind with inhibitory drugs. As a result, drug developers have largely ignored these proteins, says Kritzer. "They are considered undruggable targets, but they include some of the most direct causes of cancer, inflammation and other diseases," he says.

Kritzer will focus his technology on a specific group of proteins called transcription factors, which are in charge of turning genes on and off. "Cancer involves cell growth pathways that are getting turned on when they should be off," says Kritzer, and thus many transcription factors are known to be overactive in human cancers. For his research Kritzer will target three transcription factors implicated in cancer -- Myc, STAT3 and HSF1.

Kritzer can use yeast cells not only to make the cyclic peptides but also to sift through them to find those that inhibit these critical cancer proteins. In this manner, Kritzer notes, "we can screen up to 50 million new molecules for activity in living cells in a single week."

These new molecules will then be used as tools to understand how transcription factors contribute to cancer and other diseases. They may even form the basis for designing drugs that target these important but overlooked proteins.