Vishal Interviewed by the journal 'Science'
Science 10 September 2010:
Vol. 329. no. 5997, p. 1373
DOI: 10.1126/science.329.5997.1373
LIFE SCIENCE TECHNOLOGIES: Biomarker Hunters Probe the Proteome.
The advent of sophisticated new tools has drawn many researchers into the burgeoning field of proteomic biomarker discovery, but turning their discoveries into clinical tests is still a tall order.
THE LONG HAUL
Single-marker tests are also on the agenda of Vishal Vaidya, assistant professor of medicine at Harvard Medical School in Boston, Massachusetts, whose work also highlights the challenges of validating a clinical biomarker.
More than a decade ago, researchers at Harvard decided to look for biomarkers of kidney injury using representational difference analysis, a PCR-based technique that predated the advent of transcriptomic microarrays. The screening identified kidney injury molecule 1 (Kim-1), an immunoglobulin-like membrane protein whose expression in the urine spikes after acute kidney injury.
Vaidya joined the effort at that point. "My first project was to take cells that overexpress the Kim-1 protein, isolate this protein through regular chromatographic purification techniques, inject it into the mice, make antibodies, screen for specific epitopically distinct antibodies, and make a very conventional ELISA [enzyme-linked immunosorbent assay]," he says.
The initial assay looked good, but Vaidya and his colleagues realized that validating the biomarker in a large-scale clinical study would mean processing thousands of samples, an expensive and time-consuming proposition with ELISA. To address that, the team adapted the test to use the bead-based immunoassay system from Luminex in Austin, Texas. "We looked at that and it was fantastic—the assay was established, it was great, and we didn't need to worry about diluting urine samples. And we could do thousands of samples in just two weeks," says Vaidya.
Besides a working, clinically practical test, biomarker validation also requires a bit of social engineering. Vaidya's group and a host of collaborators finally proved the medical utility of the Kim-1 biomarker in May, just over 12 years after the Harvard team's initial discovery. "The Food and Drug Administration, the National Institutes of Health, industry, and academics—all of them got together and they all sort of came to this single point that, yes, we need better biomarkers for kidney toxicity; and if we all join hands without being too selfish, then this is going to happen," says Vaidya.
Complete article can be accessed at: http://www.sciencemag.org/products/lst_20100910.dtl