Averting Catastrophe Through Chemistry

For Chris Newgard, biology is really all about making sense of chemistry.

“Metabolomics measures body chemistry, and chemistry represents the integrated readout of all the underlying variation in the genome, the transcriptome, and the proteome,” he says. “I like to think it gives us the most integrated, molecular readout possible of a patient’s phenotype.”

As director of the Sarah W. Stedman Nutrition and Metabolism Center, Newgard has built a lab that is arguably one of the most sophisticated metabolomics labs in the country. They use mass spectrometry to resolve many of the 6,500 or so recognized metabolites in humans and to measure their concentrations in various body fluids.

With collaborators including Duke’s Svati Shah, Debbie Muoio, Laura Svetkey, William Kraus and others, he is applying those tools to identify profiles with the potential to address many clinically important questions: Which patients with heart disease will go on to have a major cardiac event and which won’t? Which individuals with insulin resistance will benefit from a weight loss program? Who is at the greatest risk of kidney failure?

As is the case with other ‘omics approaches, interpreting those profiles once you’ve got them is the biggest challenge, requiring computational power paired together with deep metabolic expertise. When Newgard and his colleagues uncover a metabolic profile in patients – especially anything unexpected – they also use studies of animals in the laboratory to get a handle on the underlying biology.

Ultimately, the vision is to boil down those complex metabolic profiles into something that could form the basis for relatively simple and clinically useful blood tests, designed to predict health problems before they happen.

They also want to understand where those metabolites come from in the first place, and what might be done to change a patient’s course. After all, our metabolomes can and do change over time. Sometimes, maybe it’s as simple as what we eat for breakfast.


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