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Award of MERIT

NIH recognizes Daniel Kim-Shapiro's pioneering sickle-cell research.

To reward outstanding researchers and sustain their work, the National Institutes of Health (NIH) occasionally awards what are termed MERIT (for Method to Extend Research in Time) grants.

Daniel Kim-Shapiro

Daniel Kim-Shapiro

If an NIH committee reviewing a grant-extension application considers the project to be exceptionally productive and promising, and if the researcher's track record with his or her previous NIH grants is stellar, the committee can, at its discretion, extend the grant for up to ten years — double the normal maximum time frame.

The advantages of a MERIT grant are obvious. With the security of long-term funding, recipients can concentrate on achieving outcomes that might require more time and patience without the distraction of reapplying for an extension after three or four years as is ordinarily required. Moreover, it's a strong signal that the NIH, one of leading scientific research funding agencies in the world, has confidence that one's project is important and likely to yield solid results.

Not surprisingly, MERIT grants are seldom awarded. The requirements are rigorous and eligibility is restricted to projects previously ranked in the top 10 percent by their review committees and among the top 5 percent of current renewal applications. Only 5 percent of all NIH grant recipients receive one, and no one, to the best of anyone's recollection, had received one on Wake Forest's Reynolda Campus.

But that changed this spring when Daniel Kim-Shapiro, professor of physics, was notified that he has received a MERIT Award from the National Heart, Lung, and Blood Institute (NHLBI) to continue his pioneering research on sickle-cell anemia.

Kim-Shapiro, who holds a Ph.D. from the University of California-Berkeley and is in his eleventh year on the Wake Forest faculty, is investigating, with collaborators that include Bruce King of chemistry and Mark Gladwin, chief of the NHLBI's vascular branch and among the world's foremost authorities in the field, the effects of nitric oxide in sickle-cell blood.

Sickle-cell anemia, which afflicts people of African descent disproportionately and is debilitating and often fatal, is caused by a mutation of the oxygen-carrying molecules in blood, called hemoglobin. Hemoglobin is carried through the bloodstream by red blood cells, which must squeeze through vessels smaller than they are to deliver oxygen to the body. In sickle-cell anemia, the red blood cells form rods and become rigid, which prevents them from passing through the apertures they must get through. Blockages form and tissues are deprived of oxygen and die. Symptoms and related maladies include severe pain, stroke, pulmonary hypertension, gastric diseases, infection, and ischemic repefusion injury — the reintroduction of oxygen into oxygen-deprived tissues.

Kim-Shapiro and his colleagues are probing the pathology of poor nitric oxide availability in the blood of sickle-cell sufferers. Nitric oxide acts as a relaxation agent that promotes free blood flow. In sickle-cell patients, red blood cells tend to break open and release their hemoglobin, which consumes the nitric oxide in the bloodstream. In something of a breakthrough, the group has found that nitrite — the salt used to preserve sausages, which can become nitrosamines, a carcinogen, when ingested in certain quantities and conditions — is converted to nitric oxide in the body. Its hypothesis, which is controversial among some sickle-cell researchers, is that nitrite could be used to generate nitric oxide and promote better blood flow in sickle-cell anemia sufferers.

Having already filed a patent for the use of nitrite for treating certain cardiovascular conditions, the group seeks to understand more thoroughly how the nitrite-to-nitric-oxide conversion process works and then to pursue possible clinical applications of the salt in sickle-cell anemia treatment.

— David Fyten
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