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  • Translational Research

    Tinkerer Turned Chemist

    Nathanael Gray, PhDNathanael Gray, PhD 

    As a boy, Nathanael Gray, PhD, was fascinated with LEGOs. "Assembling complicated structures from simple ones was very gratifying to me," says the assistant professor in the Department of Cancer Biology. He even imagined becoming a professional LEGO designer. As that dream faded, he channeled his passion into a career in chemistry, not such an unlikely choice. Chemical elements — like the interlocking toy bricks the young Nathanael snapped together into elaborate skyscrapers — constitute the basic building blocks from which medicinal chemists construct complex compounds.

    Gray became familiar with organic chemistry by working in his godfather's laboratory at the University of California at Berkeley, where he later earned a PhD in chemistry. While the director of biological chemistry at the Novartis Research Foundation, he led a team that designed inhibitors of kinases that become deregulated in cancer.

    In 2005, Dana-Farber recognized a rising star and recruited Gray as part of a strategic investment in chemical biology — expertise that is crucial to translational research, says Thomas Roberts, PhD, vice chair for research in the Department of Pediatric Oncology co-chair of Cancer Biology. "With the addition of chemical biology skills to our armamentarium, Dana-Farber can now translate basic cancer discoveries into small molecules, which previously had been the sole domain of the biotech and pharmaceutical industries."

    Chemical structure of tae684, an alk inhibitor, is shown as a ball and stick diagram.Chemical structure of TAE684, an ALK inhibitor, is shown as a ball and stick diagram. Atoms are colored by element: carbon (grey), nitrogen (blue), chlorine (green), sulfur (yellow), and oxygen (red). 

    Gray oversees a laboratory of medicinal chemists and biologists who synthesize small molecule inhibitors and use a variety of screens and assays to improve their potency, selectivity, and biological function. The overriding goals of his lab are to rigorously validate the mechanisms and targets of compounds, and to kindle the interest of biopharmaceutical companies in turning these compounds into new cancer drugs. His lab recently used an inhibitor of ALK to demonstrate that this kinase may be an appropriate target in lung cancer and neuroblastoma.

    Early pharmacological validation gives companies the data they need to pursue new therapies and shortens the drug discovery timeline, explains Gray. "Doing this up-front work for companies helps bring new agents to clinical trials more quickly."

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