Amy Wagers – focusing on stem cell biology

Twenty minutes after her weekly lab meeting is scheduled to begin, Amy Wagers rushes into a conference room on the fourth floor of the Joslin Diabetes Center, where her lab team sits, chatting around a long oval table.

“Sorry I’m late,” she calls out, closing the door behind her. “Oh good, the food’s here!”

Grabbing half a sandwich and a pickle off a catered tray, she simultaneously grabs a seat and motions for her team to begin its presentations. Lights out.

In the darkened room, all eyes turn to the illuminated white screen. There, in all its monochromic splendor, glows an enlarged image of a blood-forming hematopoietic stem cell.

At 34, Wagers is already a Principal Faculty member of the Harvard Stem Cell Institute, an assistant professor in Harvard’s new Department of Stem Cell and Regenerative Biology, and also has appointments at Harvard Medical School and Joslin.

In a remarkably short period of time, Wagers and her team have  seen their efforts propel the lab from the ranks of start-ups to those of the firmly established. If her team’s latest research into the development of muscle continues along the same track, it may some day be possible to harness the power of adult muscle stem cells to make future skeletal muscle transplant possible, offering real hope to patients with muscular dystrophy and other muscle degenerative diseases.

Embryonic stem cells are unique entities with the potential to develop into any cell type in the body. They can multiply without limit, serving as a repair system by replenishing other cells. Because of these characteristics, they may prove to be invaluable tools for fighting human disease.

Once a week, Wagers meets with her two research assistants, three postdoctoral fellows, medical fellow, and graduate student who staff her lab. Regular meetings give the scientists a chance to present their developing data. Today, it also gives Wagers a chance to have lunch. Shooting out of one meeting early, she immediately heads to another. Much of Wagers’ day is spent applying for grants and making phone calls.

Her titles bespeak formality, but dressed in blue jeans and a black fleece, her hair loose, Wagers could easily be mistaken for one of her own lab techs. But those placing their bets on the future of stem cell science look at accomplishments rather than age and titles. And last summer the W.M. Keck Foundation named Wagers a “Distinguished Young Scholar in Medical Research” providing her with $1 million to support her work with adult stem cells over five years.

Using Adult Stem Cells

There are two principal stem cell types, adult and embryonic. Embryonic stem cells are derived from a blastocyst — an early embryo — and are pluripotent, meaning a single stem cell has the ability to give rise to all of the various cell types that make up the body. Adult stem cells are found within adult tissues and are generally limited to differentiating into the various cell types of their tissue of origin.

The Wagers Lab primarily does research on two types of adult stem cells — blood-forming, or hematopoietic, stem cells, which generate all the red and white blood cells needed to deliver oxygen to body tissues, and muscle-forming, or myogenic, stem cells, which generate muscle fibers.

Bone marrow transplants, which are used to treat a range of diseases, including leukemia, lymphoma, and immunodeficiency, depend on blood-forming stem cells.

So far, blood-forming stem cells are the only adult stem cells scientists have been able to purify and use to treat human disease. However, scientists have reported isolating adult stem cells in the brain, blood vessels, skin, liver, and skeletal muscle, and are still searching for them in other parts of the body.

“[Adult stem cells] are very powerful for targets of tissue regeneration. We have been interested in making bone marrow transplants better and, similarly, making muscle cell transplant possible,” says Wagers.

Shane Mayack, a postdoctoral fellow in her third year with Wagers, studies the factors regulating hematopoietic cell mobilization. She says she interviewed with 15 labs before deciding to work with Wagers.

“I thought the types of questions she was interested in asking were really exciting and important to address, especially for the future of modern science,” Mayack says.

Because the lab focuses on asking fundamental questions about stem cells, such as what extrinsic factors influence their movement and reproduction, Wagers is building a platform of information that people in many fields can use, Mayack says.

Her Story

Over the hum of the projector, Wagers asks questions about what the lab technicians identified in the slides. They refer to the presentation as a “story.” Asked about it later, Wagers explains that a “story” is a series of scientific findings that come together to reveal something new.

Wagers’ own story began in Chicago, where she received her doctoral degree in immunology and microbial pathogenesis from Northwestern University. As an undergraduate, she signed up to be a bone marrow donor. In her senior year, she got an unexpected phone call — she matched a patient who needed a transplant. Although the patient decided not to go through with the procedure, Wagers was fascinated with the blood-forming stem cells that are utilized in the transplant. “I thought, wow, stem cells were really cool,” she recalls. She decided to do her postdoctoral fellowship training in stem cell biology, and went to Stanford to study with Irving Weismann, who since 2003 has been the director of Stanford’s Institute for Stem Cell Biology and Regenerative Medicine.

Wagers began her postdoc work studying the trafficking of blood-forming stem cells in the body. A year into her research, a rash of scientific papers were published that seemed to prove adult stem cells were pluripotent. With the debate over embryonic stem cell research becoming super-heated, the new findings took on enormous political importance.

“Folks were taking the data and saying ‘we don’t need embryonic stem cells. The blood-forming stem cell is pluripotent, and can make anything; we’ll just do bone marrow transplants and we’ll cure heart disease,’” Wagers says.

She realized the systems she had already set up to study the trafficking of stem cells were perfect to study whether or not the cells were in fact pluripotent.

In 2002, she released a paper titled “Little Evidence for Developmental Plasticity of Hematopoietic Stem Cells.” Her paper was a direct refutation of previous papers published in high-profile journals, and disproved evidence from other labs suggesting that adult stem cells were pluripotent.

“The whole idea was that stem cells run around in your blood looking for damage, and then when they find it they just become whatever it is they need to become, magically,” she says. “People still have this idea of stem cells. They’re not magic. But people want them to be,” she adds.

Embryonic and adult stem cells

“Studying adult stem cells informs embryonic stem cell research,” Wagers explains.

“I study adult skeletal muscle stem cells — they know how to make muscle. I mean, they really know how to make muscle. That is all they do — they are professional muscle-making cells,” she says.

In order to force an embryonic stem cell to make muscle, Wagers says, the best thing to do is to learn from the muscle stem cell. She says her lab would be transitioning into more embryonic stem cell research in the future.

“Our strategy is to inform ourselves in the adult [stem cell] and then take that to embryonic stem cells. We’ve just got to the level of sophistication with the adult [stem cells] that I think it’s time to move,” she says. “For human models of disease, there’s a lot of opportunity [with embryonic stem cells] that is difficult to study using adult cells.”

Because stem cell biology is a relatively new field, each question you answer gets you five more questions, Wagers says.

Being curious is one of the essential character traits of a scientist.

The most important trait according to Wagers? “Stubbornness,” she answers, laughing, “no, that’s not quite the right word. Perseverance. Ninety percent of what you’re going to do in science is not going to work. To be successful, you have to be able to forgive yourself for all the mistakes you’re going to make, and want to get up and do it again the next day. Am I going to learn something no matter whether it fails or works? I love those experiments. No matter what, unless you drop it on the floor, you’re going to learn something.”