Yale Bulletin and Calendar

November 2, 2007|Volume 36, Number 9

NIH honors chemist for innovative
work on antibodies

David Spiegel, assistant professor of organic chemistry, has received a $1.5 million National Institutes of Health (NIH) Director’s New Innovator Award that will support his work designing a “rational” approach for using antibodies to target a wide variety of cells and disease types.

The New Innovator Awards are reserved for investigators of exceptional promise, who are just beginning their careers and have not yet received a regular research grant from the NIH.

“New investigators are the future of science, and innovative ideas are its lifeblood,” says Dr. Elias Zerhouni, NIH director. “The creative scientists we recognize are well-positioned to make significant and potentially transformative discoveries in a variety of areas.”

The NIH award will fund Spiegel’s project titled “Small-Molecule Antibody Recruiting Therapeutics for Treating Human Disease,” in which he is exploring a novel approach to using antibodies that recognize a single small molecule as a universal agent for targeting and destroying many different pathogens and various types of diseased cells.

For many years, physicians and scientists have used the common small molecule dinitrophenyl (DNP) chloride in immunizations in order to generate anti-DNP antibodies as a test of the status of the immune system. Spiegel is now coupling DNP with agents that recognize pathogens like HIV or surface elements of specific cell types. He theorizes that when cells, bacteria or viruses are exposed to these compounds, they will effectively become “coated” with DNP, attract the anti-DNP antibodies and then be destroyed.

“Scientists have found that for no apparent reason, about 20% of people already have DNP antibodies in their system, and it is easy and harmless to induce DNP-antibody production,” says Spiegel. “Our task will be to rationally design DNP-compounds that recognize pathogens and act as ‘magnets’ for the antibody.

“Rational design is the key and the advantage to this approach,” Spiegel adds. “Rather than using the brute force approach of screening combinatorial libraries of synthetic compounds, we already have cell-specific and pathogen-specific targeting molecules we can use or modify.”

As a synthetic chemist, Spiegel will identify the best pathogen-targeting molecules and the best way of arranging them in relationship to DNP in order to attract DNP-antibodies to the constructed compound. As a physician, his aim is to redirect the immune system to deal as simply as possible with multiple “diseases.”

The five-year grant to Spiegel was among the first group of Innovator Awards in the NIH Roadmap for Medical Research Initiative that tests new approaches to supporting research. Awards were made to 30 researchers out of 2,200 applicants, of these, only three of the awardees, including Spiegel, are in chemistry departments. Yale cell biologist Derek Toomre also received one of the awards for his innovative work on microscopes. (See the Sept. 28 issue of the Yale Bulletin & Calendar.)

“David Spiegel possesses a stunning and eclectic background that has set the stage for an exciting career in academic science,” says Gary Brudvig, professor and chair of chemistry. “His training in chemistry and medicine combine to bring great promise to this new area of therapeutics. We are delighted that his creativity and potential as an outstanding investigator has been acknowledged through this NIH award.”

Spiegel earned his undergraduate degree with highest honors at Harvard University. He matriculated at Yale in the M.D./Ph.D. program, and due to his great interest in chemistry completed the Ph.D. portion of his program pursuing projects in organic synthesis in the laboratory of Yale chemist John Wood. After his postdoctoral training with Stuart L. Schreiber at Harvard, Spiegel joined the Yale faculty in the Department of Chemistry in July 2007.

The NIH Roadmap for Medical Research is a series of far-reaching initiatives designed to transform the nation’s medical research capabilities. The conceptual and technological breakthroughs likely to emerge from these highly innovative approaches to major research challenges are expected to speed progress toward important medical advances.

— By Janet Rettig Emanuel

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