After getting a doctorate in biochemistry in his native country, he came to Baltimore four years ago to study under the technique's pioneer, Srinivasan Chandrasegaran, at Hopkins' Bloomberg School of Public Health. Ramalingam's research has led him down the path of seeking a cure for sickle cell anemia, a painful, life-shortening blood disorder that afflicts many in his home region in southern India. In the United States, the disease affects 70,000-100,000 people, mostly African-Americans, according to the National Heart Lung and Blood Institute.
"I couldn't have done this type of research in India," said Ramalingam. "I wanted to use this technique with stem cells to treat disease."
Ramalingam's research was given a lift last month by the state. He was one of 17 researchers who was funded by the Maryland Stem Cell Research Commission, a state entity that has doled out roughly $10 million to $12 million a year in taxpayer funds since its founding in 2006.
The program helps keep Maryland competitive in stem cell research when other states have instituted similar ones to lure scientists and biotechnology companies. More than 100 researchers applied for funding from the program, many from Johns Hopkins and the University of Maryland.
"There's definitely a great demand for the awards," said Dan Gincel, the commission's director. "We're trying to figure out how to fund so many researchers."
Gincel said Ramalingam's work is interesting because his approach could have applications beyond sickle cell anemia. It could be used to treat other diseases and, for instance, modify plants and crops to make them resistant to pests.
Ramalingam received a $110,000 award two years ago from the commission to help fund his post-doctoral fellowship; the commission invested more money in his work this year because he was continuing to progress with it, Gincel said.
"The approach can be translated to many other diseases, which is what we want to see with stem cells," said Gincel.
Ramalingam is applying a relatively new technique called zinc finger nuclease, or ZFN, to try to cure sickle cell anemia. With ZFN, Ramalingam is able to target and replace specific, problem-causing sequences of the human genome with healthier genetic material.
Ramalingam chose to focus on attempting to cure sickle cell anemia because it is a hereditary single-gene disorder that's easier to focus on in the lab.
Healthy blood cells are disc-shaped and travel easily in blood vessels, carrying oxygen to organs and tissue. A blood cell affected by sickle cell anemia is sickle-shaped, and its travel through blood vessels is impeded because of the shape, leaving organs and tissue starved for oxygen.
Essentially, ZFN acts as "molecular scissors" on the human genome, Ramalingam said. He can then replace the disease-causing genetic material with healthier material derived from adult stem cells. But Ramalingam and scientists around the world using the technique still have a long way to go in studying how such a technique effects the genome.
"To modify the genome is very challenging," said Ramalingam. "This is a very basic approach. I want to check if this technique works with stem cells."
Ramalingam's adviser, Chandrasegaran, is the inventor of the ZFN technique. Hopkins holds the patent on the technique, which it has licensed to Sangamo BioSciences Inc. in California. Scientists around the world can still use the technique in their research, but if they seek to commercialize a treatment or product, they would have to license it from Sangamo, Chandrasegaran said.
If Ramalingam is successful in using the method to cure sickle cell disease, the university could apply for a new patent, Chandrasegaran said.
Chandrasegaran will guide Ramalingam's research, which will still be in the data-gathering phase in the lab for the next two years, he said. If it's still promising, the researchers will conduct testing in animals. The next step after that would be human clinical trials.
At that point, Chandrasegaran said, the technique would probably be licensed to a private company that would be able to fund the testing, which would likely cost millions of dollars.
"It's promising," Chandrasegaran said. "But it's a long way off before we can actually test it."
Sickle cell anemia
Inherited blood disorder in which the patient has sickle-shaped blood cells that impede travel through blood vessels, leaving organs and tissue starved for oxygen.
The disease affects 70,000-100,000 people in the United States, according to the National Heart Lung and Blood Institute.
More information: nhlbi.nih.gov, sicklecelldisease.org, cdc.gov