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TGen President Outlines System Medicine Approach

By Eddy Ball
June 2007

Jeffrey M. Trent
Trent, left, and Paules were both perplexed when the projector system in Rodbell Auditorium refused to recognize Trent's Mac, delaying the start of the lecture by nearly 15 minutes and forcing the speaker to step up the pace of his talk. (Photo courtesy of Steve McCaw)

statistics about TGen's high throughput RNAi
The statistics about TGen's high throughput RNAi were impressive. The group now uses an automated colony picker and has over 100,000 small interfering (si)RNAs available for its genome-wide studies. (Photo courtesy of Steve McCaw)

Jeffrey M. Trent
Trent was justifiably proud of his group's dramatic progress. "Great things can come from humble beginnings," he said toward the close of the talk. (Photo courtesy of Steve McCaw)

Rodbell Auditorium filled quickly on May 3 with scientists eager to hear Jeffrey M. Trent, Ph.D., speak on the topic "Systems Medicine in Cancer Therapeutics." In the course of his talk, the researcher discussed recent advances in his group's efforts to translate genomic discoveries into effective therapies for patients with treatment-resistant cancers.

In 2000, Trent founded the non-profit biomedical research institute Translational Genomics Research Institute or TGen, headquartered in Phoenix, Ariz., and he has been president and scientific director ever since. Prior to forming the company, Trent served for ten years at NIH, where he founded and directed the intramural division of the National Human Genome Institute that was in charge of coordinating and finalizing the Human Genome Project.

Under Trent's leadership, TGen has assembled a team of nearly 300 laboratory scientists, computer experts, biomedical engineers, clinical partners and support personnel who are taking the knowledge gained from the Human Genome Project and creating practical discoveries that will ultimately help diagnose and treat many diseases. TGen has built a network of collaborators to enhance its resources, forming relationships with such organizations as the Mayo Clinic Scottsdale, the IBM Functional Genomics and Systems Biology Group, the University of Arizona Medical School, several private companies, and a number of specialized non-profits and foundations.

"What distinguishes us," Trent observed at the beginning of his presentation, "... is that when we decided to build an institute that would be internationally recognized, we realized that we had to have an infrastructure that would be commensurate with trying to utilize the information available from the Genome Project in a major way." When TGen began its work, the group had the 53rd most powerful computer in the world - and the top third or fourth in the biomedical field.

Trent's mantra throughout his talk was that "Density matters" in systems medicine by "adding redundant information and lowering 'noise'" in pooling-based genome wide association studies. Trent and colleagues at TGen have focused primarily on cellular genomics using very high throughput RNA interference (RNAi) technology to knockdown genes systematically across the genome and determine the functional role of each gene in various cellular processes.

"While everyone talks about 'personalized' therapeutic decisions," he explained, "we believe it's going to take this computationally based process to determine the optimal disease context for any given intervention." TGen's pharmacogenomics discovery process moves through comprehensive disease profiling and drug profiling into clinical trial and mathematical modeling - matching the specific molecular context of disease with the most appropriate therapy.

Some of the most exciting work going on at TGen occurs when computational discoveries find their way to the bedsides of patients. Clinicians focus on clinical trials with targeted agents and genomics-based individualized therapy for patients in the Scottsdale Healthcare system, participants at other clinical trial sites and individuals nationwide who contact TGen as their last hope for overcoming their cancers.

Clinicians in TGen's Genomic Medicine and Individualized Therapy Service Center see only patients who have already been treated unsuccessfully elsewhere for their disease. Researchers are interested in finding a specific treatment based on identifying a target gene. However, if they are unsuccessful, the Center still offers high-quality empirical treatment. In addition to disease remission and progression, patient outcomes include comparison of treatment time at TGen with previous treatment time in other venues.

Trent's talk was hosted by Senior Scientist Richard Paules, Ph.D., director of the Microarray Group at NIEHS, and sponsored jointly by the Laboratory of Pharmacology and Chemistry, the Laboratory of Molecular Toxicology and the Director's Challenge Program in Oxidative Stress.

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