Cell Mates

Cell Mates

David Bodine enlists Colby researchers in a bid to unlock the genetic mysteries of blood disorders

By Steve Heacock

David Bodine ‰76, center, confers with researchers Serena Vayda ‰03, left, and André Pilon ‰03 at the National Institutes of Health‰s Genetics and Molecular Biology Branch laboratory. Vayda and Pilon are members of Bodine‰s team, which investigates causes of red blood cell disorders.
Photo by Robert Visser
Don't let the sweatpants fool you. Bodine is a leader in his field, and his research could lead to groundbreaking ways to treat serious blood disorders.

Next year will be Bodine's 23rd at the NIH, where he recently was named chief of the Genetics and Molecular Biology Branch. The promotion last fall is the latest in an accomplished career that began in 1984 at the NIH's Clinical Hematology Branch of the National Heart, Lung, and Blood Institute. As a senior staff fellow, he launched his own lab in 1988, and five years later he was recruited to the NHGRI's Hematopoiesis Section of the Genetics and Molecular Biology Branch. He received tenure in 1995. He has won a slew of awards, including the NIH National Research Service Award and the NHGRI Mentor of the Year Award.

This is no small thing, coming from one of the largest and most esteemed centers of biomedical research in the world, an organization that employs more than 19,000 people. The NHGRI alone employs 750. Bodine's branch consists of approximately 60 researchers and scientists, and his lab is made up of a dozen scientists.

He clearly has put his stamp on his lab.

"He has this saying, every day,— said André Pilon '03, one of a long line of Colby students and graduates who have gone to work with Bodine. "He walks in every morning and asks us, 'What are you doing to thrust back the boundaries of ignorance today?'—

It appears that Bodine and his colleagues are doing plenty.

They are hard at work studying the genetic underpinnings of hematopoiesis, the process of blood formation. Hematopoietic stem cells, found in bone marrow, turn into red blood cells and the many different types of white blood cells. Anemia, leukemia, and a variety of other blood diseases disrupt the process.

"Very broadly, we're talking about red cells that are arresting their maturation just short of being good red blood cells,— Bodine said one blustery November day, as windswept rain lashed Building 49. "We are learning how to regulate red cell production in animals. Gene therapy? Someday, I hope. But a drug that would do an end run around invasive gene therapy would be just as desirable. Our job is to come up with the targets, understand why the cells work and don't work, and determine what is correctable.—

One of the curious aspects of some of these blood disorders is their propensity to afflict certain populations. Some African, Asian, and Mediterranean populations are more prone than others to hereditary blood diseases like thalassemia and other anemias. Approximately 100,000 babies are born worldwide every year with severe forms of thalassemia, which most often limit life expectancy to between 20 and 30 years but also can cause death in newborns. Genetic evidence suggests that in Sicily, for example, 6 to 12 percent of the population could transmit thalassemia to their children.

"Some of the broader questions,— Bodine said, "are why are there so many people with this disease gene in these particular geographical areas? And why doesn't natural selection make it go away?— In the case of thalassemia, the affected red blood cells provide a poor host for the parasite that causes malaria, which is endemic to these parts of the world, so it is an evolutionary tradeoff.

Pilon's work focuses on gene regulation, figuring out which genetic "pathways— are wrong in defective red blood cells. He studies mice that are missing a key protein called a transcription factor. He analyzes red blood cell maturation in these mice to determine why the hematopoietic cells do not generate the proper number and quality of red cells. He has discovered that these cells do not divide correctly and cannot mature (or differentiate) into the cells they need to become.

"My work is to find out the molecular biology that lies under all of that,— Pilon said. "The DNA is the
genetic material or code in the cells. RNA is the message that tells the cell to make the transcription factor that, in turn, triggers production of other proteins needed for cell division. Certain genes are 'turned on' when this process happens, and I'm trying to figure out why they aren't turned on in these defective cells. I have to see how the transcription factor causes a gene to be activated or repressed.—
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