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Marletta wins grant to develop blood substitute

Michael Marletta

Michael Marletta, is working on a blood substitute that could carry oxygen. (Photo: Peg Skorpinski)

Blood is one of those things you take for granted, until you start losing it. If you’re injured near a hospital, then you’ll probably be okay. But if you are injured in a less developed country miles from the nearest refrigerator, or if you are a soldier on a foreign battlefield, or even if you are injured at home but have an unusual blood type, you may not be so lucky.

In these situations lives could be saved by a blood substitute that maintains the supply of oxygen to vital organs. Michael Marletta, current chair of the Department of Chemistry and a researcher in the interdisciplinary Quantitative Biomedical Research Institute (QB3), has identified proteins that could safely transport oxygen in the blood.

The blood substitute idea evolved from the studies carried out in Marletta’s lab by postdoc Elizabeth Boon (now assistant professor of chemistry at SUNY Stonybrook). Two former lab members will remain active in the research program — Stephen Cary (now at Genentech) and Jonathan Winger (currently a postdoc with Berkeley chemistry professor John Kuriyan).

The potential of Marletta’s work has so impressed T. Gary Rogers, the CEO of Dreyer’s Grand Ice Cream and the head of the Rogers Family Foundation, that he has granted Marletta $250,000 to continue his research.

The funding will allow Marletta to bridge the so-called “valley of death” between university research and the marketplace. These Rogers “Bridging the Gap” grants are intended to allow researchers to advance promising work to a point where investors will fund commercialization.

“We’ve proved the concept in the relatively safe confines of a test tube. Now we need to see if it will work in animals,” says Marletta. “If it does, then investors will be lured by the potential. But we need to move the research forward, and this grant will allow us to do that.”

Most attempts at blood substitutes have started with hemoglobin, the natural iron-based molecule in red blood cells that carries oxygen. But hemoglobin was designed by nature to selectively bind and release oxygen from inside red blood cells. When hemoglobin circulates freely in the blood, things can go haywire.

Hemoglobin interacts with nitric oxide (NO), a dissolved gas in the bloodstream that plays a critical role in regulating blood pressure. The oxygenated form of hemoglobin reacts with NO, destroying both the NO and the ability of the hemoglobin to deliver oxygen. The end result is no oxygen and no NO.

What is needed are proteins that can freely circulate in the blood, binding and releasing oxygen like red blood cells, but not interfering with nitric oxide and its regulation of blood pressure. Marletta’s research group has identified just such a group of proteins.

Marletta, whose expertise runs from understanding protein function to inorganic biochemistry (the biological properties of non-carbon compounds), has studied the role of NO in the body and has identified a class of proteins, called H-NOX (Heme-Nitric Oxide and/or OXygen) binding proteins, that control the delivery of NO. These proteins are found in bacteria, fruit flies and humans, indicating that the role of NO is an early adaptation in the evolution of cellular forms of life.

“We have already achieved our first goal,” says Marletta. “We have identified several candidates among the H-NOX family of proteins that would be suitable for genetic modification to give them the desirable oxygen and NO binding properties. The next goal will be to produce enough quantities of the proteins for testing in animals.”

Marletta foresees a blood substitute that could be stored simply as a package of dry chemicals in an otherwise empty intravenous fluid bag. Sterile water could be added and the resulting blood substitute infused like standard IV fluids. “The life-saving potential is tremendous,” says Marletta.

 

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